Publications by authors named "Ertugrul Kilic"

131 Publications

Inflammatory Cytokines are in Action: Brain Plasticity and Recovery after Brain Ischemia Due to Delayed Melatonin Administration.

J Stroke Cerebrovasc Dis 2021 Sep 18;30(12):106105. Epub 2021 Sep 18.

Department of Physiology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey. Electronic address:

Objectives: Post-ischemic inflammation leads to apoptosis as an indirect cause of functional disabilities after the stroke. Melatonin may be a good candidate for the stroke recovery because of its anti-inflammatory effects. Therefore, we investigated the effect of melatonin on inflammation in the functional recovery of brain by evaluating ipsilesional and contralesional alterations.

Materials And Methods: Melatonin (4 mg/kg/day) was intraperitoneally administered into the mice from the 3 to the 55 day of the post-ischemia after 30 min of middle cerebral artery occlusion.

Results: Melatonin produced a functional recovery by reducing the emigration of the circulatory leukocytes and the local microglial activation within the ischemic brain. Overall, the expression of the inflammation-related genes reduced upon melatonin treatment in the ischemic hemisphere. On the other hand, the expression level of the inflammatory cytokine genes raised in the contralateral hemisphere at the 55 day of the post-ischemia. Furthermore, melatonin triggers an increase in the iNOS expression and a decrease in the nNOS expression in the ipsilateral hemisphere at the earlier times in the post-ischemic recovery. At the 55 day of the post-ischemic recovery, melatonin administration enhanced the eNOS and nNOS protein expressions.

Conclusions: The present molecular, biological, and histological data have revealed broad anti-inflammatory effects of melatonin in both hemispheres with distinct temporal and spatial patterns at different phases of post-stroke recovery. These outcomes also established that melatonin act recruitment of contralesional rather than of ipsilesional.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106105DOI Listing
September 2021

Inhibition of Fatty Acid Synthesis Aggravates Brain Injury, Reduces Blood-Brain Barrier Integrity and Impairs Neurological Recovery in a Murine Stroke Model.

Front Cell Neurosci 2021 16;15:733973. Epub 2021 Aug 16.

Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.

Inhibition of fatty acid synthesis (FAS) stimulates tumor cell death and reduces angiogenesis. When SH-SY5Y cells or primary neurons are exposed to hypoxia only, inhibition of FAS yields significantly enhanced cell injury. The pathophysiology of stroke, however, is not only restricted to hypoxia but also includes reoxygenation injury. Hence, an oxygen-glucose-deprivation (OGD) model with subsequent reoxygenation in both SH-SY5Y cells and primary neurons as well as a murine stroke model were used herein in order to study the role of FAS inhibition and its underlying mechanisms. SH-SY5Y cells and cortical neurons exposed to 10 h of OGD and 24 h of reoxygenation displayed prominent cell death when treated with the Acetyl-CoA carboxylase inhibitor TOFA or the fatty acid synthase inhibitor cerulenin. Such FAS inhibition reduced the reduction potential of these cells, as indicated by increased NADH /NAD ratios under both and stroke conditions. As observed in the OGD model, FAS inhibition also resulted in increased cell death in the stroke model. Stroke mice treated with cerulenin did not only display increased brain injury but also showed reduced neurological recovery during the observation period of 4 weeks. Interestingly, cerulenin treatment enhanced endothelial cell leakage, reduced transcellular electrical resistance (TER) of the endothelium and contributed to poststroke blood-brain barrier (BBB) breakdown. The latter was a consequence of the activated NF-κB pathway, stimulating MMP-9 and ABCB1 transporter activity on the luminal side of the endothelium. In conclusion, FAS inhibition aggravated poststroke brain injury as consequence of BBB breakdown and NF-κB-dependent inflammation.
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http://dx.doi.org/10.3389/fncel.2021.733973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415573PMC
August 2021

Protective Effect of Lutein/Zeaxanthin Isomers in Traumatic Brain Injury in Mice.

Neurotox Res 2021 Oct 15;39(5):1543-1550. Epub 2021 Jun 15.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.

Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood-brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1β), interleukin 6 (IL-6), and NF-κB levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway.
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http://dx.doi.org/10.1007/s12640-021-00385-3DOI Listing
October 2021

The role of circadian rhythm in the regulation of cellular protein profiles in the brain.

Turk J Med Sci 2020 Dec 28. Epub 2020 Dec 28.

Background/aim: Circadian rhythm plays a significant role in the regulation of almost all kinds of physiological processes. Besides this it may also have a direct or indirect effect on the neurodegenerative processes, including Alzheimer's disease, Parkinson's disease, and ischemic stroke. Therefore, the identification of circadian rhythm related proteins is crucial to be able to understand the molecular mechanism of the circadian rhythm and to define new therapeutic target for the treatment of degenerative disorders.

Materials And Methods: To identify the light and dark regulated proteins, 8-12 weeks, male Balb/C mice were used at two different time points (Morning (Zeitgeber time-0 (ZT0)) and midnight (ZT18)) under physiological conditions. Therefore, brain tissues were analyzed via liquid chromatography tandem-mass spectrometry.

Results: A totally of 1621 different proteins were identified between ZT0 and ZT18 mice. Among these proteins, 23 proteins were differentially expressed (p<0.05 and fold change 1.4) in ZT18 mice, 11 upregulated (AKAP10, ALDOC, BLK, NCALD, NFL, PDE10A, PICAL, PSMB6, RL10, SH3L3, and SYNJ1), and 12 downregulated (AT2A2, AT2B1, CPNE5, KAP3, MAON, NPM, PI51C, PPR1B, SAM50, TOM70, TY3H, and VAPA) as compared with ZT0 mice.

Conclusion: Taken together, here we identified circadian rhythm related proteins, and our further analyzed revealed that these proteins play significant roles in molecular function, membrane trafficking, biogenesis, cellular process, metabolic process, and neurodegenerative disorders such as Parkinson?s disease.
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http://dx.doi.org/10.3906/sag-2010-336DOI Listing
December 2020

Neural Progenitor Cell-Derived Extracellular Vesicles Enhance Blood-Brain Barrier Integrity by NF-κB (Nuclear Factor-κB)-Dependent Regulation of ABCB1 (ATP-Binding Cassette Transporter B1) in Stroke Mice.

Arterioscler Thromb Vasc Biol 2021 03 17;41(3):1127-1145. Epub 2020 Dec 17.

Department of Neurology (L.Z., I.G., Y.K., X.Z., M.H., M.S.W., M.B., T.R.D.), University Medical Center Göttingen, Germany.

Objective: Extracellular vesicles (EVs) derived from neural progenitor cells enhance poststroke neurological recovery, albeit the underlying mechanisms remain elusive. Since previous research described an enhanced poststroke integrity of the blood-brain barrier (BBB) upon systemic transplantation of neural progenitor cells, we examined if neural progenitor cell-derived EVs affect BBB integrity and which cellular mechanisms are involved in the process. Approach and Results: Using in vitro models of primary brain endothelial cell (EC) cultures as well as co-cultures of brain ECs (ECs) and astrocytes exposed to oxygen glucose deprivation, we examined the effects of EVs or vehicle on microvascular integrity. In vitro data were confirmed using a mouse transient middle cerebral artery occlusion model. Cultured ECs displayed increased ABCB1 (ATP-binding cassette transporter B1) levels when exposed to oxygen glucose deprivation, which was reversed by treatment with EVs. The latter was due to an EV-induced inhibition of the NF-κB (nuclear factor-κB) pathway. Using a BBB co-culture model of ECs and astrocytes exposed to oxygen glucose deprivation, EVs stabilized the BBB and ABCB1 levels without affecting the transcellular electrical resistance of ECs. Likewise, EVs yielded reduced Evans blue extravasation, decreased ABCB1 expression as well as an inhibition of the NF-κB pathway, and downstream matrix metalloproteinase 9 (MMP-9) activity in stroke mice. The EV-induced inhibition of the NF-κB pathway resulted in a poststroke modulation of immune responses.

Conclusions: Our findings suggest that EVs enhance poststroke BBB integrity via ABCB1 and MMP-9 regulation, attenuating inflammatory cell recruitment by inhibition of the NF-κB pathway. Graphic Abstract: A graphic abstract is available for this article.
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http://dx.doi.org/10.1161/ATVBAHA.120.315031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901534PMC
March 2021

Adipose-derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR-25.

J Extracell Vesicles 2020 10 11;10(1):e12024. Epub 2020 Nov 11.

University Medical Center Goettingen Department of Neurology Goettingen Germany.

Grafted mesenchymal stem cells (MSCs) yield neuroprotection in preclinical stroke models by secreting extracellular vesicles (EVs). The neuroprotective cargo of EVs, however, has not yet been identified. To investigate such cargo and its underlying mechanism, primary neurons were exposed to oxygen-glucose-deprivation (OGD) and cocultured with adipose-derived MSCs (ADMSCs) or ADMSC-secreted EVs. Under such conditions, both ADMSCs and ADMSC-secreted EVs significantly reduced neuronal death. Screening for signalling cascades being involved in the interaction between ADMSCs and neurons revealed a decreased autophagic flux as well as a declined p53-BNIP3 activity in neurons receiving either treatment paradigm. However, the aforementioned effects were reversed when ADMSCs were pretreated with the inhibitor of exosomal secretion GW4869 or when Hrs was knocked down. In light of miR-25-3p being the most highly expressed miRNA in ADMSC-EVs interacting with the p53 pathway, further in vitro work focused on this pathway. Indeed, a miR-25-3p oligonucleotide mimic reduced cell death, whereas the anti-oligonucleotide increased autophagic flux and cell death by modulating p53-BNIP3 signalling in primary neurons exposed to OGD. Likewise, native ADMSC-EVs but not EVs obtained from ADMSCs pretreated with the anti-miR-25-3p oligonucleotide (ADMSC-EVs) confirmed the aforementioned in vitro observations in C57BL/6 mice exposed to cerebral ischemia. The infarct size was reduced, and neurological recovery was increased in mice treated with native ADMSC-EVs when compared to ADMSC-EVs. ADMSCs induce neuroprotection by improved autophagic flux through secreted EVs containing miR-25-3p. Hence, our work uncovers a novel key factor in naturally secreted ADMSC-EVs for the regulation of autophagy and induction of neuroprotection in a preclinical stroke model.
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http://dx.doi.org/10.1002/jev2.12024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710129PMC
October 2020

Lithium modulates miR-1906 levels of mesenchymal stem cell-derived extracellular vesicles contributing to poststroke neuroprotection by toll-like receptor 4 regulation.

Stem Cells Transl Med 2021 Mar 4;10(3):357-373. Epub 2020 Nov 4.

Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.

Lithium is neuroprotective in preclinical stroke models. In addition to that, poststroke neuroregeneration is stimulated upon transplantation of mesenchymal stem cells (MSCs). Preconditioning of MSCs with lithium further enhances the neuroregenerative potential of MSCs, which act by secreting extracellular vesicles (EVs). The present work analyzed whether MSC preconditioning with lithium modifies EV secretion patterns, enhancing the therapeutic potential of such derived EVs (Li-EVs) in comparison with EVs enriched from native MSCs. Indeed, Li-EVs significantly enhanced the resistance of cultured astrocytes, microglia, and neurons against hypoxic injury when compared with controls and to native EV-treated cells. Using a stroke mouse model, intravenous delivery of Li-EVs increased neurological recovery and neuroregeneration for as long as 3 months in comparison with controls and EV-treated mice, albeit the latter also showed significantly better behavioral test performance compared with controls. Preconditioning of MSCs with lithium also changed the secretion patterns for such EVs, modifying the contents of various miRNAs within these vesicles. As such, Li-EVs displayed significantly increased levels of miR-1906, which has been shown to be a new regulator of toll-like receptor 4 (TLR4) signaling. Li-EVs reduced posthypoxic and postischemic TLR4 abundance, resulting in an inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, decreased proteasomal activity, and declined both inducible NO synthase and cyclooxygenase-2 expression, all of which culminated in reduced levels of poststroke cerebral inflammation. Conclusively, the present study demonstrates, for the first time, an enhanced therapeutic potential of Li-EVs compared with native EVs, interfering with a novel signaling pathway that yields both acute neuroprotection and enhanced neurological recovery.
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http://dx.doi.org/10.1002/sctm.20-0086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900596PMC
March 2021

Physiological and pharmacological roles of melatonin in the pathophysiological components of cellular injury after ischemic stroke

Turk J Med Sci 2020 11 3;50(SI-2):1655-1664. Epub 2020 Nov 3.

Department of Physiology, School of Medicine, İstanbul Medipol University, İstanbul, Turkey

Apart from its metabolic or physiological functions, melatonin has a potent cytoprotective activity in the physiological and pathological conditions. It is synthetized by the pineal gland and released into the blood circulation but particularly cerebrospinal fluid in a circadian manner. It can also easily diffuse through cellular membranes due its small size and lipophilic structure. Its cytoprotective activity has been linked to its potent free radical scavenger activity with the desirable characteristics of a clinically- reliable antioxidant. Melatonin detoxifies oxygen and nitrogen-based free radicals and oxidizing agents, including the highly toxic hydroxyl-and peroxynitrite radicals, initiating cellular damage. However, the cytoprotective activity of melatonin is complex and cannot be solely limited to its free radical scavenger activity. It regulates cellular signaling pathways through receptor– dependent and independent mechanisms. Most of these downstream molecules, such as PI3K/AKT pathway components, also contribute to the cytoprotective effects of melatonin. In this term, melatonin is a promising molecule for the treatment of neurodegenerative disorders, such as ischemic stroke, which melatonin reduces ischemic brain injury in animal models of ischemic stroke. It regulates also circadian rhythm proteins after ischemic stroke, playing roles in cellular survival. In this context, present article summarizes the possible role of melatonin in the pathophysiological events after ischemic stroke.
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http://dx.doi.org/10.3906/sag-2008-32DOI Listing
November 2020

Two boron-containing compounds affect the cellular viability of SH-SY5Y cells in an in vitro amyloid-beta toxicity model.

Turk J Biol 2020 19;44(4):208-214. Epub 2020 Aug 19.

Department of Medical Biology, School of Medicine, University of Health Sciences, İstanbul Turkey.

Boron is a naturally occurring trace element found in organic and inorganic complexes. Boron-containing compounds are required for living organisms for diverse metabolic functions, including nitrogen fixation in microorganisms, cell wall stability in plants, and bone and carbohydrate metabolism in animals. The number of studies about the effect of boron in biological model systems is very limited; so far, there has been no study on the correlation between boron and amyloid-beta toxicity. Here, we investigated the possible effects of 2 boron-containing compounds-sodium borate decahydrate and boric acid-against amyloid-beta toxicity. In our in vitro amyloid-beta toxicity model, we showed that these 2 compounds increase the survival of the SH-SY5Y cells. Furthermore, boron in these 2 forms increases the expression of Sirt1, which has protective functions against cellular stress. The compounds also change the expressions of GSK-3α/β; by doing so, boron may contribute to the stimulation of intracellular prosurvival pathways. This is the first experimental study indicating the prosurvival effect of boron in an amyloid-beta toxicity model.
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http://dx.doi.org/10.3906/biy-2001-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478136PMC
August 2020

Neuroprotective effect of lithium in cold- induced traumatic brain injury in mice.

Behav Brain Res 2020 08 30;392:112719. Epub 2020 May 30.

Istanbul Medipol University, Regenerative and Restorative Medical Research Center, Istanbul, Turkey; Istanbul Medipol University, Faculty of Medicine, Dept. of Physiology, Istanbul, Turkey. Electronic address:

Apart from its well-established therapeutic activity on bipolar disorder and depression, lithium exerts neuroprotective activity upon neurodegenerative disorders, such as traumatic brain injury (TBI). However, the cellular signaling mechanisms mediating lithium's neuroprotective activity and long-term dose- and time-dependent effects on close and remote proximity are largely unknown. Herein, we tested prophylactic and acute effects of lithium (2 mmol/kg) after cold- induced TBI. In both conditions, treatments with lithium resulted in reduced infarct volume and apoptosis. Its acute treatment resulted in the increase of Akt, ERK-1/2 and GSK-3 α/β phosphoylations. Interestingly, its prophylactic treatment instead resulted in decreased phosphorylations of Akt, ERK-1/2, p38, JNK-1 moderately and GSK-3 α/β significantly. Then, we tested subacute (35-day follow-up) role of low (0.2 mmol/kg) and high dose (2 mmol/kg) lithium and revealed that high dose lithium group was the most mobile so the least depressed in the tail suspension test. Anxiety level was assessed by light-dark test, all groups' anxiety levels were decreased with time, but lithium had no effect on anxiety like behavior. When subacute effects of injury and drug treatment were evaluated on the defined brain regions, infarct volume was decreased in the high dose lithium group significantly. In contrast to other brain regions, hippocampal atrophies were observed in both lithium treatment groups, which were significant in the low dose lithium group in both hemispheres, which was associated with the reduced cell proliferation and neurogenesis. Our data demonstrate that lithium treatment protects neurons from TBI. However, long term particularly low-dose lithium causes hippocampal atrophy and decreased neurogenesis.
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http://dx.doi.org/10.1016/j.bbr.2020.112719DOI Listing
August 2020

Lentivirally administered glial cell line-derived neurotrophic factor promotes post-ischemic neurological recovery, brain remodeling and contralesional pyramidal tract plasticity by regulating axonal growth inhibitors and guidance proteins.

Exp Neurol 2020 09 23;331:113364. Epub 2020 May 23.

Research Institute for Health Sciences and Technologies (SABITA), Regenerative and Restorative Medicine Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey; Dept. of Physiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey. Electronic address:

Owing to its potent longterm neuroprotective and neurorestorative properties, glial cell line-derived neurotrophic factor (GDNF) is currently studied in neurodegenerative disease clinical trials. However, little is known about the longterm effect of GDNF on neurological recovery, brain remodeling and neuroplasticity in the post-acute phase of ischemic stroke. In a comprehensive set of experiments, we examined the effects of lentiviral GDNF administration after ischemic stroke. GDNF reduced neurological deficits, neuronal injury, blood-brain barrier permeability in the acute phase in mice. As compared with control, enhanced motor-coordination and spontaneous locomotor activity were noted in GDNF-treated mice, which were associated with increased microvascular remodeling, increased neurogenesis and reduced glial scar formation in the peri-infarct tissue. We observed reduced brain atrophy and increased plasticity of contralesional pyramidal tract axons that crossed the midline in order to innervate denervated neurons in the ipsilesional red and facial nuclei. Contralesional axonal plasticity by GDNF was associated with decreased abundance of the axonal growth inhibitors brevican and versican in contralesional and ipsilesional brain tissue, reduced abundance of the growth repulsive guidance molecule ephrin b1 in contralesional brain tissue, increased abundance of the midline growth repulsive protein Slit1 in contralesional brain tissue and reduced abundance of Slit1's receptor Robo2 in ipsilesional brain tissue. These data indicate that GDNF potently induces longterm neurological recovery, peri-infarct brain remodeling and contralesional neuroplasticity, which are associated with the fine-tuned regulation of axonal growth inhibitors and guidance molecules that facilitate the growth of contralesional corticofugal axons in the direction to the ipsilesional hemisphere.
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http://dx.doi.org/10.1016/j.expneurol.2020.113364DOI Listing
September 2020

The effect of systemic rifampicin treatment on inferior alveolar nerve regeneration in rats following crush injury.

Eur J Oral Sci 2020 06 1;128(3):183-189. Epub 2020 Apr 1.

Department of Physiology, Istanbul Medipol University, Istanbul, Turkey.

Axonal regeneration of the inferior alveolar nerve (IAN) is a therapeutic target for functional recovery after peripheral nerve injury. Rifampicin exerts anti-apoptotic, anti-inflammatory, and anti-oxidant effects on nerve tissues that may enhance functional recovery after peripheral nerve injury. The aim of the present study was to evaluate the therapeutic effects of systemic rifampicin following IAN crush injury. Following the nerve crush injuries of the IAN, 24 Sprague-Dawley rats were randomly divided into three groups to receive daily intraperitoneal injections of either vehicle, 5 mg kg rifampicin, or 20 mg kg rifampicin. Twenty-four days after induction of nerve injuries, Fluorogold (FG) was injected over the mental foramen for the evaluation of neuronal survival. At the end of the four-week period, histologic and histomorphometric examination of IAN samples were performed and FG positive cells were counted in the trigeminal ganglion sections. FG positive cells were significantly more frequent in the 20 and 5 mg kg rifampicin groups than in the vehicle-treated group. Electron microscopic analyses revealed that the percentage of axons with optimum g-ratio was significantly lower in the vehicle group than in both treatment groups. In conclusion, systemic rifampicin treatment can enhance peripheral nerve regeneration.
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http://dx.doi.org/10.1111/eos.12691DOI Listing
June 2020

Evidence that osteogenic and neurogenic differentiation capability of epidural adipose tissue-derived stem cells was more pronounced than in subcutaneous cells

Turk J Med Sci 2020 12 17;50(8):1825-1837. Epub 2020 Dec 17.

Department of Neurosurgery, Başkent University, İstanbul, Turkey

Background/aim: The management of dura-related complications, such as the repairment of dural tears and reconstruction of large dural defects, remain the most challenging subjects of neurosurgery. Numerous surgical techniques and synthetic or autologous adjuvant materials have emerged as an adjunct to primary dural closure, which may result in further complications or side effects. Therefore, the subcutaneous autologous free adipose tissue graft has been recommended for the protection of the central nervous system and repairment of the meninges. In addition, human adipose tissue is also a source of multipotent stem cells. However, epidural adipose tissue seems more promising than subcutaneous because of the close location and intercellular communication with the spinal cord. Herein, it was aimed to define differentiation capability of both subcutaneous and epidural adipose tissue-derived stem cells (ASCs).

Materials And Methods: Human subcutaneous and epidural adipose tissue specimens were harvested from the primary incisional site and the lumbar epidural space during lumbar spinal surgery, and ASCs were isolated.

Results: The results indicated that both types of ASCs expressed the cell surface markers, which are commonly expressed stem cells; however, epidural ASCs showed lower expression of CD90 than the subcutaneous ASCs. Moreover, it was demonstrated that the osteogenic and neurogenic differentiation capability of epidural adipose tissue-derived ASCs was more pronounced than that of the subcutaneous ASCs.

Conclusion: Consequently, the impact of characterization of epidural ASCs will allow for a new understanding for dural as well as central nervous system healing and recovery after an injury.
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http://dx.doi.org/10.3906/sag-2001-76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775714PMC
December 2020

Melatonin affects the release of exosomes and tau-content in in vitro amyloid-beta toxicity model.

J Clin Neurosci 2020 Mar 12;73:237-244. Epub 2020 Feb 12.

University of Health Sciences, Medical School, Department of Medical Biology, Istanbul, Turkey. Electronic address:

Background: Recent studies have been revealed that oxidative damage is the main cause of aging and age-related neurodegenerative diseases like Alzheimer's disease (AD). Melatonin is secreted from the pineal gland and its secretion has been found to be altered in AD. In the last decade the role of exosomes in spreading toxic proteins and inducing the propagation of diseases like AD has been discussed. However, it is not known how melatonin affects the amount of exosomes released from the cells and the content of the exosomes.

Objective: Herein, we investigated the possible role of melatonin treatment in the releasing of exosomes and exosomal tau content in an in vitro Aβ toxicity model.

Method: SH-SY5Y cell line was used. The optimum concentration of Aβ was determined by cell viability and cell proliferation tests. Melatonin (100 µM) was applied before and after Aβ application. Total exosomes isolated from cell culture media were immunoprecipitated. The amount of released exosomes and their tau content were analyzed by Western blots.

Results: Our data demonstrated for the first time that melatonin treatment clearly affected the amount of released exosomes. It would decrease the amyloid beta load and toxicity by inhibiting exosome release. We also demonstated that melatonin also affected the level of tau carried by exosomes depending on whether melatonin was applied before or after Aβ application.

Conclusion: It is considered that the effect of melatonin in the release of exosomes and exosomal tau content would contribute the development of therapeutic strategies in AD and related disorders.
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http://dx.doi.org/10.1016/j.jocn.2019.11.046DOI Listing
March 2020

Distal approach for percutaneous radiofrequency thermocoagulation of lumbar medial branches in patients with lumbar facet arthropathy: A retrospective analysis.

Agri 2020 Jan;32(1):31-37

Department of Anesthesia, Şehitkamil State Hospital, Gaziantep, Turkey.

Objectives: Lumbar facet (zygapophysial) arthropathy is a common cause of chronic lower back pain, and percutaneous radiofrequency denervation of the facet joints appears to be an effective treatment that yields long-term improvement. A technique utilising a distal approach to place the needle parallel to the medial branch has recently come into common use. In the present study, a technique incorporating a distal approach and an A-P fluoroscopic view was investigated.

Methods: In this study, clinical charts of 164 patients with lumbar facet syndrome who had undergone RFTC (radiofrequency thermocoagulation) of facet-joint medial branches were retrospectively evaluated. The success rate of percutaneous radiofrequency thermocoagulation of facet-joint medial branches performed utilising a distal approach with an A-P view was evaluated. NRS (numeric rank score) pain scores and subjective patient-reported global responses were measured.

Results: Of the patients, responses were rated as excellent by 46 (28.0%), good by 67 (40.8%), fair by 21 (12.8%) and poor by 30 (18.2%). The median duration of pain relief was 7.3 months. In the 113 patients who reported excellent or good responses, the median duration of pain relief was 10.2 months.

Conclusion: Radiofrequency thermocoagulation for facet arthropathy is a safe and effective treatment option that is well-tolerated. We suggest that a distal approach with an A-P view for facet radiofrequency thermocoagulation is a viable alternative to other approaches.
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http://dx.doi.org/10.14744/agri.2019.15921DOI Listing
January 2020

Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice.

Biomedicines 2020 Feb 3;8(2). Epub 2020 Feb 3.

Department of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, Turkey.

Cisplatin (CP) is one of the most preferred platinum-containing antineoplastic drugs. However, even in nontoxic plasma concentrations, it may cause kidney injury. To be able to increase its effective pharmacological dose, its side effects need to be regarded. Diet restriction (DR) has been demonstrated to improve cellular survival in a number of disorders. In this context, we investigated the role of DR in CP-induced nephrotoxicity (CPN). Besides alternate DR, animals were exposed to DR for 3 days prior or after CP treatment. Here, we observed that both 3 days of DR reverses the nephrotoxic effect of CP, which was associated with improved physiological outcomes, such as serum creatine, blood-urea nitrogen and urea. These treatments significantly increased phosphorylation of survival kinases PI3K/Akt and ERK-1/2 and decreased the level of stress kinase JNK were noted. In addition, the activation level of signal transduction mediator p38 MAPK phosphorylation was higher particularly in both three-day DR groups. Next, animals were fed with carbohydrate-, protein- or fat-enriched diets in the presence of CP. Results indicated that not only fasting but also dietary content itself may play a determinant role in the severity of CPN. Our data suggest that DR is a promising approach to reduce CPN by regulating metabolism and cell signaling pathways.
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http://dx.doi.org/10.3390/biomedicines8020023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168297PMC
February 2020

CCL11 Differentially Affects Post-Stroke Brain Injury and Neuroregeneration in Mice Depending on Age.

Cells 2019 Dec 26;9(1). Epub 2019 Dec 26.

Department of Neurology, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany.

CCL11 has recently been shown to differentially affect cell survival under various pathological conditions including stroke. Indeed, CCL11 promotes neuroregeneration in neonatal stroke mice. The impact of CCL11 on the adult ischemic brain, however, remains elusive. We therefore studied the effect of ectopic CCL11 on both adolescent (six-week) and adult (six-month) C57BL6 mice exposed to stroke. Intraperitoneal application of CCL11 significantly aggravated acute brain injury in adult mice but not in adolescent mice. Likewise, post-stroke neurological recovery after four weeks was significantly impaired in adult mice whilst CCL11 was present. On the contrary, CCL11 stimulated gliogenesis and neurogenesis in adolescent mice. Flow cytometry analysis of blood and brain samples revealed a modification of inflammation by CCL11 at subacute stages of the disease. In adolescent mice, CCL11 enhances microglial cell, B and T lymphocyte migration towards the brain, whereas only the number of B lymphocytes is increased in the adult brain. Finally, the CCL11 inhibitor SB297006 significantly reversed the aforementioned effects. Our study, for the first time, demonstrates CCL11 to be a key player in mediating secondary cell injury under stroke conditions. Interfering with this pathway, as shown for SB297006, might thus be an interesting approach for future stroke treatment paradigms.
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http://dx.doi.org/10.3390/cells9010066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017112PMC
December 2019

Interaction of melatonin and Bmal1 in the regulation of PI3K/AKT pathway components and cellular survival.

Sci Rep 2019 12 13;9(1):19082. Epub 2019 Dec 13.

Regenerative and Restorative Medicine Research Center, Istanbul Medipol University, 34810, Istanbul, Turkey.

The circadian rhythm is driven by a master clock within the suprachiasmatic nucleus which regulates the rhythmic secretion of melatonin. Bmal1 coordinates the rhythmic expression of transcriptome and regulates biological activities, involved in cell metabolism and aging. However, the role of Bmal1 in cellular- survival, signaling, its interaction with intracellular proteins, and how melatonin regulates its expression is largely unclear. Here we observed that melatonin increases the expression of Bmal1 and both melatonin and Bmal1 increase cellular survival after oxygen glucose deprivation (OGD) while the inhibition of Bmal1 resulted in the decreased cellular survival without affecting neuroprotective effects of melatonin. By using a planar surface immunoassay for PI3K/AKT signaling pathway components, we revealed that both melatonin and Bmal1 increased phosphorylation of AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3αβ, and p70S6K. In contrast, inhibition of Bmal1 resulted in decreased phosphorylation of these proteins, which the effect of melatonin on these signaling molecules was not affected by the absence of Bmal1. Besides, the inhibition of PI3K/AKT decreased Bmal1 expression and the effect of melatonin on Bmal1 after both OGD in vitro and focal cerebral ischemia in vivo. Our data demonstrate that melatonin controls the expression of Bmal1 via PI3K/AKT signaling, and Bmal1 plays critical roles in cellular survival via activation of survival kinases.
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http://dx.doi.org/10.1038/s41598-019-55663-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910929PMC
December 2019

Normobaric oxygen treatment improves neuronal survival functional recovery and axonal plasticity after newborn hypoxia-ischemia.

Behav Brain Res 2020 02 13;379:112338. Epub 2019 Nov 13.

School of Medicine, Department of Physiology, Istanbul Medipol University, 34810, Istanbul, Turkey; Regenerative and Restorative Medical Research Center (REMER), Istanbul Medipol University, 34810, Istanbul, Turkey. Electronic address:

Background: Newborn hypoxia ischemia (HI) is one of the most prevalent cases in the emergency and can result from fetal hypoxia during delivery. In HI, restricted blood supply to the fetal brain may cause epilepsy or mental disorders.

Methods: In the present study, seven-day-old pups were subjected HI and treated with different normobaric oxygen (NBO) concentrations (21%, 70% or 100%). In the acute phase, we analyzed infarct area, disseminate neuronal injury and surviving neurons. In addition, we studied the regulation of PTEN and MMP-9 proteins which were suggested to be activated by HI in the ischemic tissue. Moreover, long-term effects of NBO treatments were evaluated with open field, rotarod and Barnes maze tests. We also examined axonal plasticity with EGFP-AAV injection.

Results: Here, we demonstrate that hyperoxic NBO concentration causes an increase in cellular survival and a decrease in the number of apoptotic cells, meanwhile inhibiting the proteins involved in cellular death mechanisms. Moreover, we found that hyperoxia decreases anxiety, promotes motor coordination and improve spatial learning and memory. Notably that axonal sprouting was promoted by hyperoxia.

Conclusion: Our data suggest that NBO is a promising approach for the treatment of newborn HI, which encourage proof-of-concept studies in newborn.
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http://dx.doi.org/10.1016/j.bbr.2019.112338DOI Listing
February 2020

Myelosuppression and acute hematological complications of sulfur mustard exposure in victims of chemical terrorism.

Toxicol Lett 2020 Jan 31;318:92-98. Epub 2019 Oct 31.

University of Health Sciences, Dept. of Medical CBRN Defense, Etlik, 06010, Ankara, Turkey.

Sulfur mustard (SM) is a vesicant chemical warfare agent. Recent studies reported alleged use of SM by non-state actors in Syria and Iraq. It has been shown that SM induced immunological and hematological complications. The aim of this study was to determine acute toxic effects of SM exposure on hematological parameters. Blood samples from a group of Syrian exposed to SM in 2016 were taken daily during the follow-up of the patients in intensive care unit. Initial leukocytosis was observed in all patients (100%) on the first 48 h after exposure. Following leukocytosis, isolated lymphopenia was observed in all patients (100%) between 2 and 4 days. A decrease in hemoglobin level was noted in five patients (62.5%) between 4 and 5 days. Thrombocytopenia was observed in 75% of patients between 4 and 6 days for mild cases and between 9 and 11 days for severe cases. Three patients (37.5%) developed distinct leucopenia/neutropenia on 11 and 12 days. It was observed that human exposure to high dose of SM has direct toxic effect on hematological cells and bone marrow. New strategies on treatment of SM-induced myelosuppression could reduce the effects of hematological complications and could increase the survival rate in these patients.
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http://dx.doi.org/10.1016/j.toxlet.2019.10.017DOI Listing
January 2020

Evidence that melatonin downregulates Nedd4-1 E3 ligase and its role in cellular survival.

Toxicol Appl Pharmacol 2019 09 17;379:114686. Epub 2019 Jul 17.

Istanbul Medipol University, School of Medicine, Dept. of Physiology, Istanbul, Turkey; Istanbul Medipol University, Regenerative and Restorative Medical Research Center, Istanbul, Turkey. Electronic address:

Indolamine melatonin structurally resembles non-covalent proteasome inhibitors; however, the role of ubiquitin proteasome system (UPS) in neuronal survival and how melatonin carries out UPS inhibition remain largely unknown. With the use of melatonin treated cells, we evaluated the expression of Nedd4-1, an E3 ligase, how melatonin regulates its activity and its relationship with neuronal survival. Nedd4-1 was upregulated in the hypoxic condition in both control and Nedd4-1 overexpressed cells and melatonin treatment reversed its expression in both normoxic and hypoxic conditions, which was associated with increased cellular survival. Melatonin had no effect on the expression of Nedd4-1 at mRNA level. However, when melatonin was administered along with protein synthesis inhibitor cycloheximide, protein level of Nedd4-1 was further reduced, indicating that melatonin possibly downregulates Nedd4-1 after its synthesis. Notably, co-immunoprecipitation analyses followed by Liquid chromatography-Mass Spectrometry (LC-MS/MS) revealed that melatonin may dissociate ribosomal proteins, such as RS19, RL23A, and nucleophosmin from Nedd4-1, while 40S ribosomal protein S7 and 60S ribosomal protein L35 came into contact with Nedd4-1 upon melatonin treatment. By using IPA analyses, we obtained further data indicated novel target molecules of melatonin in hypoxic conditions, including OTOF, SF3B2, IPO5, ST13, FGFR3, Mx1/Mx2, playing roles in RNA splicing and trafficking, growth factor and interferon signaling. Here, we described a new insight into the role of melatonin in UPS functioning by proposing a molecular mechanism through which melatonin regulates Nedd4-1.
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http://dx.doi.org/10.1016/j.taap.2019.114686DOI Listing
September 2019

The Association between HbA1c Levels, Olfactory Memory and Cognition in Normal, Pre-Diabetic and Diabetic Persons.

Endocr Metab Immune Disord Drug Targets 2020 ;20(2):198-212

Istanbul Medipol University, Restorative and Regenerative Medicine Center, Istanbul, Turkey.

Background And Aim: Recent data have shown that olfactory dysfunction is strongly related to Alzheimer's Disease (AD) that is often preceded by olfactory deficits suggesting that olfactory dysfunction might represent an early indicator of future cognitive in prediabetes.

Methods: We have applied to a group of normal (n=15), prediabetic (n=16) and type 2 diabetic outpatients (n=15) olfactory testing, 1.5-T MRI scanner and detailed cognitive evaluation including the standard Mini-Mental State Examination (MMSE) form, Short Blessed Test (SBT), Letter Fluency Test (LFT) and the category fluency test with animal, Fruit and Vegetable Naming (CFT).

Results: We have shown that Odour Threshold (OT), Discrimination (OD), and Identification (OI) scores and most cognitive test results were significantly different in the prediabetes and diabetes group compared to those in the control group. OD and OT were significantly different between the prediabetes and diabetes group, although the cognitive test results were only significantly different in the prediabetes and diabetes group compared to those in the control group. In evaluating the association between OI, OT, OD scores and specific cognitive tests, we have found, that impaired olfactory identification was the only parameter that correlated significantly with the SBT both in the pre-diabetes and diabetes group. Although spot glucose values were only correlated with OT, HbA1c levels were correlated with OT, OD, and OI, as well as results of the letter fluency test suggesting that HbA1c levels rather than the spot glucose values play a critical role in specific cognitive dysfunction.

Conclusion: To the best of our knowledge, this is the first prospective study to demonstrate a strong association between olfactory dysfunction and specific memory impairment in a population with prediabetes and diabetes suggesting that impaired olfactory identification might play an important role as a specific predictor of memory decline.
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http://dx.doi.org/10.2174/1871530319666190614121738DOI Listing
November 2020

Evidence of sulfur mustard exposure in victims of chemical terrorism by detection of urinary β-lyase metabolites.

Clin Toxicol (Phila) 2020 01 10;58(1):36-44. Epub 2019 May 10.

Department of Medical CBRN Defense, University of Health Sciences, Ankara, Turkey.

Sulfur mustard (SM) is a vesicant chemical warfare agent. Ocular, dermal, and respiratory systems are the primary targets of SM exposure. The aims of this study were to perform a quantitative analysis of β-lyase metabolites of SM as 1,1'-sulfonylbis[2-(methylthio) ethane] (SBMTE) in urine samples of chemical casualties and to investigate the relationship between the measured SBMTE levels and the severity of characteristic symptoms of SM poisoning. A bioanalytical method which is based on titanium (III) chloride reduction of β-lyase metabolites was employed to analyze urine samples of individuals ( = 13, collected 30 h after SM exposure) using gas chromatography-tandem mass spectrometry. Various levels of SBMTE were measured in urine samples of seven individuals, confirming SM exposure for each. There was a correlation observed between measured levels of SBMTE in human urine samples and severity of clinical findings including ocular, respiratory, and cutaneous lesions of SM. In combination with clinical examination, measurement of SBMTE levels in human urine could be used as a prognostic factor for clinical outcomes in victims of SM exposure. This bioanalytical verification is also important for the documentation of alleged use of SM. SBMTE is an unambiguous biomarker of potential SM poisoning as it does not exist in urine samples of an unexposed population. Quantitation of urinary SBMTE concentrations in victims of SM could be used in order to enable improved interpretation of clinical findings.
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http://dx.doi.org/10.1080/15563650.2019.1614190DOI Listing
January 2020

Acute and Post-acute Neuromodulation Induces Stroke Recovery by Promoting Survival Signaling, Neurogenesis, and Pyramidal Tract Plasticity.

Front Cell Neurosci 2019 12;13:144. Epub 2019 Apr 12.

Department of Physiology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey.

Repetitive transcranial magnetic stimulation (rTMS) has gained interest as a non-invasive treatment for stroke based on the data promoting its effects on functional recovery. However, the exact action mechanisms by which the rTMS exert beneficial effects in cellular and molecular aspect are largely unknown. To elucidate the effects of high- and low-frequency rTMS in the acute-ischemic brain, we examined how rTMS influences injury development, cerebral blood flow (CBF), DNA fragmentation, neuronal survival, pro- and anti-apoptotic protein activations after 30 and 90 min of focal cerebral ischemia. In addition, inflammation, angiogenesis, growth factors and axonal outgrowth related gene expressions, were analyzed. Furthermore, we have investigated the effects of rTMS on post-acute ischemic brain, particularly on spontaneous locomotor activity, perilesional tissue remodeling, axonal sprouting of corticobulbar tracts, glial scar formation and cell proliferation, in which rTMS was applied starting 3 days after the stroke onset for 28 days. In the high-frequency rTMS received animals reduced DNA fragmentation, infarct volume and improved CBF were observed, which were associated with increased Bcl-xL activity and reduced Bax, caspase-1, and caspase-3 activations. Moreover, increased angiogenesis, growth factors; and reduced inflammation and axonal sprouting related gene expressions were observed. These results correlated with reduced microglial activation, neuronal degeneration, glial scar formation and improved functional recovery, tissue remodeling, contralesional pyramidal tract plasticity and neurogenesis in the subacute rTMS treated animals. Overall, we propose that high-frequency rTMS in stroke patients can be used to promote functional recovery by inducing the endogenous repair and recovery mechanisms of the brain.
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http://dx.doi.org/10.3389/fncel.2019.00144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474396PMC
April 2019

The therapeutic role of minocycline in Parkinson's disease.

Drugs Context 2019 6;8:212553. Epub 2019 Mar 6.

Department of Neurology, Faculty of Medicine, Alaaddin Keykubat University, Alanya, Turkey.

Minocycline, a semisynthetic tetracycline-derived antibiotic, has been shown to exert anti-apoptotic, anti-inflammatory, and antioxidant effects. Furthermore, there is rapidly growing evidence suggesting that minocycline may have some neuroprotective activity in various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease (PD), Huntington's disease, and multiple sclerosis. In this perspective review, we summarize the preclinical and clinical findings suggesting the neuroprotective role of minocycline in PD.
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http://dx.doi.org/10.7573/dic.212553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408180PMC
March 2019

Minocycline Increases in-vitro Cortical Neuronal Cell Survival after Laser Induced Axotomy.

Curr Clin Pharmacol 2020 ;15(2):105-109

Department of Physiology, Istanbul Medipol University, School of Medicine, Istanbul, Turkey

Background: Antibiotic therapies targeting multiple regenerative mechanisms have the potential for neuroprotective effects, but the diversity of experimental strategies and analyses of non-standardised therapeutic trials are challenging. In this respect, there are no cases of successful clinical application of such candidate molecules when it comes to human patients.

Methods: After 24 hours of culturing, three different minocycline (Sigma-Aldrich, M9511, Germany) concentrations (1 μM, 10 μM and 100 μM) were added to the primary cortical neurons 15 minutes before laser axotomy procedure in order to observe protective effect of minocycline in these dosages.

Results: Here, we have shown that minocycline exerted a significant neuroprotective effect at 1 and 100μM doses. Beyond confirming the neuroprotective effect of minocycline in a more standardised and advanced in-vitro trauma model, our findings could have important implications for future studies that concentrate on the translational block between animal and human studies.

Conclusion: Such sophisticated approaches might also help to conquer the influence of humanmade variabilities in critical experimental injury models. To the best of our knowledge, this is the first study showing that minocycline increases in-vitro neuronal cell survival after laser-axotomy.
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http://dx.doi.org/10.2174/1574884714666190226093119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579254PMC
September 2021

Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice.

Mol Biol Rep 2019 Feb 8;46(1):241-250. Epub 2018 Nov 8.

Animal Nutrition Department, School of Veterinary Medicine, Firat University, Elazig, Turkey.

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently no FDA approved therapies. TBI results in oxidative stress due to the overproduction of reactive oxygen species and overwhelming of the endogenous antioxidant mechanisms. Recently, it has been reported that antioxidants including phytochemicals have a protective role against oxidative damage and inflammation after TBI. To analyze the effects of a naturally occurring antioxidant molecule, allyl isothiocyanate (AITC), on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways in TBI, a cryogenic injury model was induced in mice. Here, we showed that AITC administered immediately after the injury significantly decreased infarct volume and blood-brain barrier (BBB) permeability. Protein levels of proinflammatory cytokines interleukin-1β (IL1β) and interleukin-6 (IL6), glial fibrillary acidic protein (GFAP) and NF-κB were decreased, while Nrf2, growth-associated protein 43 (GAP43) and neural cell adhesion molecule levels were increased with AITC when compared with vehicle control. Our results demonstrated that the antioxidant molecule AITC, when applied immediately after TBI, provided beneficial effects on inflammatory processes while improving infarct volume and BBB permeability. Increased levels of plasticity markers, as well as an antioxidant gene regulator, Nrf2, by AITC, suggest that future studies are warranted to assess the protective activities of dietary or medicinal AITC in clinical studies.
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http://dx.doi.org/10.1007/s11033-018-4465-4DOI Listing
February 2019

Radiofrequency thermocoagulation combined with pulsed radiofrequency for gasserian ganglion blockage.

Agri 2018 Oct;30(4):179-182

Department of Anaesthesiology, Reanimation and Pain, Dr. Ersin Arslan Research and Training Hospital, Gaziantep, Turkey.

Objectives: Trigeminal neuralgia (TN) has been effectively treated by radiofrequency thermocoagulation (RFT) of the gasserian ganglion. Recently, pulsed radiofrequency (PRF) is becoming an alternative therapy for patients with trigeminal neuralgia. It is unclear whether the combination of RFT with PRF may decrease post-operative complications while maintaining longterm pain relief.

Methods: Twelve patients with idiopathic TN who had undergone combined RFT and PRF of the gasserian ganglion were evaluated. PRF (42 °C, 45V, 20 ms, 120 seconds) was administered, and then RFT (65 °C, 90 seconds) was performed to the gasserian ganglion. The post-operative pain relief and complications were evaluated at 1, 6, 12 and, 24 months after treatment.

Results: 10 patients (83.3%) reported significant pain relief (VAS 3) at 1 month following the treatment, while 8 patients (66.6%) at 6 months, 5 patients (41.6) at 12 months, and 2 patients (16.6%) at 24 months were pain-free. Two of the patients did not have pain relief (VAS ≥3), and 2 patients were still pain-free by the 24th month. The mean time of pain relief was 14 months. One patient had numbness in the tongue for about a year, while in the other patients, no serious complications were reported.

Conclusion: A combination of RFT with PRF could help eliminate postoperative complications of trigeminal neuralgia. We sugesst that combining RFT and PRF therapy may serve to decrease the side effects but not increase the pain relief.
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http://dx.doi.org/10.5505/agri.2018.88261DOI Listing
October 2018

Effects of systemic erythropoietin treatment and heterogeneous xenograft in combination on bone regeneration of a critical-size defect in an experimental model.

J Craniomaxillofac Surg 2018 Nov 20;46(11):1919-1923. Epub 2018 Sep 20.

Department of Physiology, Istanbul Medipol University, Istanbul, Turkey.

The aim of the present study was to evaluate the effects of systemic EPO treatment alone or in combination with xenogenic bone graft augmentation on bone regeneration. Eleven adult male Sprague-Dawley rats were used in the present study. Rats were subjected to bilateral 5 mm critical size bone defects on the parietal bones under general anaesthesia. Right parietal bone defects were augmented with xenogenic bone graft and left parietal bone defect was left empty. Rats were randomly assigned for one of the two groups. One group of rats received (i) vehicle (n = 6) and other group received (ii) EPO (500IU kg/day) (n = 5). EPO treatment was continued for 28 days. Vascularization was analysed by immunohistochemical staining of CD31 (PECAM-1) and new bone formation was histomorphometrically evaluated. Xenogenic graft augmentation enhanced bone formation and vascularization significantly in either vehicle or EPO treated groups (p < 0.05). Histomorphometric results of angiogenesis was similar in the EPO treated group and the control group. However, angiogenesis was significantly higher in the combination of systemic EPO treatment with graft augmentation than graft augmentation alone (p < 0.01). Graft augmentation for treatment of critical size bone defects seems essential for proper bone healing. Results of the present study suggest that EPO potentiates the regenerative processes of augmented bone defects.
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http://dx.doi.org/10.1016/j.jcms.2018.09.015DOI Listing
November 2018

Quadratus Lumborum Block III for Postoperative Pain After Percutaneous Nephrolithotomy.

Turk J Anaesthesiol Reanim 2018 Aug 1;46(4):272-275. Epub 2018 Aug 1.

Deparment of Urology, Dr. Ersin Arslan Training and Research Hospital, Gaziantep, Turkey.

Objective: An effective pain control is important in early mobilization and returning to normal daily life following percutaneous nephrolithotomy (PCNL) operations. The use of an intraoperative local anaesthetic or postoperative analgesic has been reported for pain control in PCNL. Transmuscular quadratus block (QLB III) is a regional anaesthetic technique applied under ultrasound guidance. The aim of this study was to investigate the effectiveness of QLB III on postoperative pain in PCNL.

Methods: This prospective, randomized, double-blinded study was carried out at the Dr Ersin Arslan Training and Research Hospital between December 2016 and March 2017. The QLB III block was administered to a total of 44 patients who had undergone elective PCNL under spinal anaesthesia. While half of the patients (Group S, n=22) received 0.2 cc kg of 0.9% saline, the other half (Group Q, n=22) received 0.2 mL kg of 0.0125 isobaric bupivacain with QLB III. For all patients, the pain level was measured using the visual analog scale (VAS), and the morphine consumptions through patient-controlled analgesia (PCA) were recorded at the postoperative 4, 8, 12, 24, and 48 hours.

Results: The postoperative VAS was found to be statistically significantly higher at the 8, 12, and 24 hour in Group S (p<0.05). The postoperative morphine consumption was determined to be statistically significantly higher at the 4, 8, 12, and 24 hour in Group S (p<0.05).

Conclusion: The QLB III was observed to be effective in pain control and reducing morphine consumption during the postoperative 48 hours follow-up after PCNL.
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http://dx.doi.org/10.5152/TJAR.2018.92331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101721PMC
August 2018
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