Publications by authors named "Luiza Silva Lopes"

16 Publications

  • Page 1 of 1

Phosphorylation of S6 Protein as a Potential Biomarker in Surgically Treated Refractory Epilepsy.

Dev Neurosci 2020 11;42(5-6):230-236. Epub 2021 Mar 11.

Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, Brazil.

The tuberous sclerosis complex (TSC), focal cortical dysplasia IIB (FCD IIB), and hemimegalencephaly (HME) exhibit similar molecular features that are dependent on the hyperactivation of the mTOR pathway. They are all associated with refractory epilepsy and the need for surgical resection with varying outcomes. The phosphorylated protein S6 (pS6) is a downstream target of mTOR, whose increased expression might indicate mTOR hyperactivation, but which is also present when there is no alteration in the pathway (such as in FCD type I). We have performed immunohistochemical marking and quantification of pS6 in resected brain specimens of 26 patients clinically and histologically diagnosed with TSC, FCD IIB, or HME and compared this data to a control group of 25 patients, to measure the extent of pS6 positivity and its correlation with clinical aspects. Our results suggest that pS6 may serve as a reliable biomarker in epilepsy and that a greater percentage of pS6 marking can relate to more severe forms of mTOR-dependent brain anomalies.
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http://dx.doi.org/10.1159/000514006DOI Listing
November 2021

Transcranial ultrasonography as a reliable instrument for the measurement of the cerebral ventricles in rats with experimental hydrocephalus: a pilot study.

Childs Nerv Syst 2021 06 26;37(6):1863-1869. Epub 2021 Feb 26.

Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Bandeirantes Av., 3900, Ribeirão Preto, SP, 14049-900, Brazil.

Purposes: Demonstrate that transcranial ultrasonography (TUS) scanning is viable and useful as a diagnostic method in experimental hydrocephalus, as well as to compare measurements of cerebral and ventricular width obtained from TUS scans of hydrocephalic rats with post-mortem anatomical specimens, aiming for the development of accurate criteria to establish ventricular enlargement and progression of hydrocephalus subsequently.

Methods: Thirty-five male Wistar rats were used. Following hydrocephalus induction, they underwent a transcranial ultrasound scan to measure cerebral and ventricular dimensions, in the fourth and 21 post-induction days. By the end of the experiments, measurements obtained from TUS scans were compared with actual values as seen in the post-mortem specimens of each animal.

Results: Ventricular dilation could be clearly visualized in hydrocephalic animals. We performed intraclass correlation coefficient and linear regression analyses that have demonstrated a precise correlation between measurements of TUS scans and post-mortem specimens; we have found a similarity of 0,95 for the cerebral diameter and 0,97 for ventricular width.

Conclusions: Transcranial ultrasonography is a useful and reliable diagnostic tool for experimental hydrocephalus; also, it can be used to assess the progression of ventriculomegaly in animal models of hydrocephalus.
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http://dx.doi.org/10.1007/s00381-021-05070-6DOI Listing
June 2021

Kaolin-induced hydrocephalus causes acetylcholinesterase activity dysfunction following hypothalamic damage in infant rats.

Brain Res 2019 12 26;1724:146408. Epub 2019 Aug 26.

Department of Surgery and Anatomy of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address:

In hydrocephalus, the progressive accumulation of cerebrospinal fluid (CSF) causes dilatation of the lateral ventricles affecting the third ventricle and diencephalic structures such as the hypothalamus. These structures play a key role in the regulation of several neurovegetative functions by the production of the hormones. Since endocrine disturbances are commonly observed in hydrocephalic children, we investigated the impact of progressive ventricular dilation on the hypothalamus of infant rats submitted to kaolin-induced hydrocephalus. Seven-day-old infant rats were submitted to hydrocephalus induction by kaolin 20% injection method. After 14 days, the animals were decapitated and brain was collected to analyze mitochondrial function, neuronal activity by acetylcholinesterase (AChE) enzyme, oxidative damage, glial activation, and, neurotransmission-related proteins and anti-apoptotic processes in the hypothalamus. The hydrocephalic animals showed reduction in respiratory rates in the States of phosphorylation (P < 0.01) and non-phosphorylation (P < 0.05); increase in AChE activity in both the cytosol (P < 0.05) and the membrane (P < 0.01); decrease in synaptophysin (P < 0.05) and Bcl-2 (P < 0.05) contents and; increase in protein carbonyl (P < 0.01), GFAP (P < 0.01) and Iba-1 (P < 0.05) levels. The results demonstrate that ventricular dilation causes hypothalamic damage characterized by cholinergic dysfunction and suggests further investigation of the synthesis and secretion of hormones to generate new approaches and to assist in the treatment of hydrocephalic patients with hormonal alterations.
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http://dx.doi.org/10.1016/j.brainres.2019.146408DOI Listing
December 2019

Intraperitoneal cannabidiol attenuates neonatal germinal matrix hemorrhage-induced neuroinflamation and perilesional apoptosis.

Neurol Res 2019 Nov 5;41(11):980-990. Epub 2019 Aug 5.

Pediatric neurosurgery division, Ribeirão Preto School of Medicine, University of São Paulo , Ribeirão Preto , Brazil.

. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of cannabidiol in germinal matrix hemorrhage. . 112 Wistar rat pups (P7) were submitted to an experimental collagenase induced model of GMH. Inflammatory response and neuronal death were analyzed both at the perilesional area as at the distant ipsilateral CA1 hippocampal area. Immunohistochemistry for GFAP and caspase 3 was used. The ipsilateral free water content was assessed for stimation of cerebral edema, and neurodevelopment and neurofunctional tests were conducted. . Reduction of reactive astrocytosis was observed both in the perilesional area 24 hours and 14 days after the hemorrhage lesion (p < 0.001) and in the of the ipsilateral hippocampal CA1 14 days after the hemorrhage lesion (p < 0.05) in the treated groups. Similarly, there was a reduction in the number of Caspase 3-positive astrocytes in the perilesional area in the treated groups 24 hours after the hemorrhage lesion (p < 0.001). Finally, we found a significant increase in the weight of the rats treated with cannabidiol. . The treatment of GMH with cannabidiol significantly reduced the number of apoptotic cells and reactive astrocytes in the perilesional area and the ipsilateral hippocampus. In addition, this response was sustained 14 days after the hemorrhage. These results corroborate our hypothesis that cannabidiol is a potential neuroprotective agent in the treatment of germinal matrix hemorrhage.
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http://dx.doi.org/10.1080/01616412.2019.1651487DOI Listing
November 2019

Behavioral and Biochemical Features of the Course and Surgical Treatment of Experimental Obstructive Hydrocephalus in Young Rats.

Dev Neurosci 2019 18;41(1-2):34-43. Epub 2019 Apr 18.

Division of Pediatric Neurosurgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.

Introduction: Hydrocephalus is a multifactorial disease, affecting the dynamics of cerebrospinal fluid (CSF) and leading to severe neurological impairment in children; in spite of the recent advances in hydrocephalus research, it has many physiopathological aspects that still remain poorly understood, especially after treatment.

Objectives: To analyze the clinical, radiological, histopathological, and biochemical aspects of kaolin-induced hydrocephalus in an experimental model, both in the acute phase and after shunt treatment, by means of behavioral tests, magnetic resonance imaging (MRI) scans, histopathological studies, and level of inflammatory interleukins in the CSF.

Methods: Seven-day-old Wistar rats were used and subdivided into three subgroups: treated hydrocephalic (n = 24), untreated hydrocephalic (n = 17), and controls (n = 5). The hydrocephalic groups underwent cisternal injection of 15% kaolin for induction of hydrocephalus at 7 days of age. The treated group was submitted to a ventricular-subcutaneous shunt (VSCS) 1 week after induction. All animals were euthanized at 21 days of age. They underwent motor function and memory testing as well as brain MRI scans. Histopathological analysis for glial fibrillary acidic protein and Ki-67 was done, and CSF was collected for measurement of IL-1β, IL-6, and TNF-α.

Results: The average time to reach the water maze platform was highest in the untreated hydrocephalic group. The magnetization transfer rates were 37.21 and 33.76 before and after shunting, respectively. The mean astrocyte counts were 2.45, 1.36, and 90.5 for shunted, untreated, and control animals, respectively. The mean CSF IL-1β concentrations were 62.3 and 249.6 pg/mL, the average IL-6 levels were 104.2 and 364.7 pg/mL, and the average TNF-α values were 4.9 and 170.5 pg/mL for the treated hydrocephalic group and the untreated group, respectively.

Conclusions: Pups treated with a CSF shunt showed better performance on memory tests. VSCS did not revert demyelination caused by hydrocephalus. Likewise, reactive astrocytosis and cell proliferation over the germinal matrix were not reversed after shunting. Hydrocephalic animals had raised levels of inflammatory interleukins, which returned to normal after treatment.
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http://dx.doi.org/10.1159/000497433DOI Listing
March 2020

A new model of experimental hemispherotomy in young adult Rattus norvegicus: a neural tract tracing and SPECT in vivo study.

J Neurosurg 2018 Jun 1:1-14. Epub 2018 Jun 1.

1Laboratory of Pediatric Neurosurgery and Developmental Neuropathology, Department of Surgery and Anatomy.

OBJECTIVEThe objective of this study was to describe a new experimental model of hemispherotomy performed on laboratory animals.METHODSTwenty-six male young adult Wistar rats were distributed into two groups (surgery and control). The nonfluorescent anterograde neurotracer biotinylated dextran amine (BDA; 10,000 MW) was microinjected into the motor cortex area (M1) according to The Rat Brain in Stereotaxic Coordinates atlas to identify pathways and fibers disconnected after the experimental hemispherectomy. SPECT tomographic images of 99mTc hexamethylpropyleneamine oxime were obtained to verify perfusion in functioning areas of the disconnected and intact brain. A reproducible and validated surgical procedure is described in detail, including exact measurements and anatomical relationships. An additional 30 rodents (n = 10 rats per group) were divided into naïve, sham, and hemispherotomy groups and underwent the rotarod test.RESULTSCortico-cortical neural pathways were identified crossing the midline and contacting neuronal perikarya in the contralateral brain hemisphere in controls, but not in animals undergoing hemispherotomy. There was an absence of perfusion in the left side of the brain of the animals undergoing hemispherotomy. Motor performance was significantly affected by brain injuries, increasing the number of attempts to maintain balance on the moving cylinder in the rotarod test at 10 and 30 days after the hemispherotomy, with a tendency to minimize the motor performance deficit over time.CONCLUSIONSThe present findings show that the technique reproduced neural disconnection with minimal resection of brain parenchyma in young adult rats, thereby duplicating the hemispherotomy procedures in human patients.
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http://dx.doi.org/10.3171/2017.12.JNS171150DOI Listing
June 2018

Hyperbaric oxygen therapy reduces astrogliosis and helps to recovery brain damage in hydrocephalic young rats.

Childs Nerv Syst 2018 06 18;34(6):1125-1134. Epub 2018 Apr 18.

Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo - USP, Bandeirantes Av., 3900, Ribeirão Preto, São Paulo, 14049-090, Brazil.

Purpose: We investigated the possible beneficial effects that hyperbaric oxygen therapy could offer in different brain structures affected by ventriculomegaly in pup rats submitted to experimental hydrocephalus.

Methods: Seven-day-old Wistar rats were submitted to hydrocephalus by intracisternal injection of 10% kaolin into the cisterna magna. The animals were divided into four groups: control (n = 5); control with HBOT (3ATA/2 h/day) (n = 5); untreated hydrocephalic (n = 10); hydrocephalic treated with HBOT (3ATA/2 h/day) (n = 10). The treatment with HBOT was performed daily for 14 days post-induction of hydrocephalus. To evaluate the response to treatment, behavioral tests (open field, Morris water maze, and activity monitor) were performed. After 14 days, the animals were euthanized, and the brain was removed for histological (hematoxylin-eosin and solochrome-cyanine) and immunohistochemical (GFAP and Ki-67) studies.

Results: The hyperbaric treatment, although not causing changes in ventricular enlargement, resulted in a significant improvement in the behavioral performance (p = 0.0001), with greater agility and exploration of the environment, preservation of spatial memory, and greater learning capacity (p = 0.0001). Through the immunohistochemical study, the astrocytic activity (glial fibrillary acidic protein) in the corpus callosum (p = 0.0001) and in the germinative matrix (p = 0.0033) was significantly reduced as compared to that in the H group.

Conclusion: The results suggest that hyperbaric treatment bettered the behavioral performance and offered benefits to the structures affected by the ventricular increase helping to recover the brain damages. In this way, the HBOT it can be considered an adjuvant therapy for the treatment of hydrocephalus.
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http://dx.doi.org/10.1007/s00381-018-3803-0DOI Listing
June 2018

Environmental enrichment reduces brain damage in hydrocephalic immature rats.

Childs Nerv Syst 2017 Jun 5;33(6):921-931. Epub 2017 Apr 5.

Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 3900 Bandeirantes Avenue, Ribeirão Preto, SP, 14049-900, Brazil.

Purpose: We investigate the effects of environmental enrichment (EE) on morphological alterations in different brain structures of pup rats submitted to hydrocephalus condition.

Methods: Hydrocephalus was induced in 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. Ventricular dilatation and magnetization transfer to analyze myelin were assessed by magnetic resonance. Hydrocephalic and control rats exposed to EE (n = 10 per group) were housed in cages with a tunnel, ramp, and colored plastic balls that would emit sound when touched. The walls of the housing were decorated with colored adhesive tape. Moreover, tactile and auditory stimulation was performed daily throughout the experiment. Hydrocephalic and control rats not exposed to EE (n = 10 per group) were allocated singly in standard cages. All animals were weighed daily and exposed to open-field conditions every 2 days until the end of the experiment when they were sacrificed and the brains removed for histology and immunohistochemistry. Solochrome cyanine staining was performed to assess the thickness of the corpus callosum. The glial fibrillary acidic protein method was used to evaluate reactive astrocytes, and the Ki67 method to assess cellular proliferation in the subventricular zone.

Results: The hydrocephalic animals exposed to EE showed better performance in Open Field tests (p < 0.05), while presenting lower weight gain. In addition, these animals showed better myelination as revealed by magnetization transfer (p < 0.05). Finally, the EE group showed a reduction in reactive astrocytes by means of glial fibrillary acidic protein immunostaining and preservation of the proliferation potential of progenitor cells.

Conclusion: The results suggest that EE can protect the developing brain against damaging effects caused by hydrocephalus.
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http://dx.doi.org/10.1007/s00381-017-3403-4DOI Listing
June 2017

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus.

Childs Nerv Syst 2017 Mar 17;33(3):419-428. Epub 2016 Dec 17.

Department of Surgery and Anatomy, Division of Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, 3900 Av. dos Bandeirantes, Ribeirao Preto, SP, 14049-900, Brazil.

Purpose: We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus.

Methods: Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies.

Results: The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group.

Conclusions: We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.
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http://dx.doi.org/10.1007/s00381-016-3313-xDOI Listing
March 2017

Validation of a New Minimally Invasive Intracranial Pressure Monitoring Method by Direct Comparison with an Invasive Technique.

Acta Neurochir Suppl 2016 ;122:97-100

University of São Paulo, Sao Paulo, Brazil.

In this chapter we present in vivo experiments with a new minimally invasive method of monitoring intracranial pressure (ICP). Strain gauge deformation sensors are externally glued onto the exposed skull. The signal from these sensors is amplified, filtered, and sent to a computer with appropriate software for analysis and data storage. Saline infusions into the spinal channel of rats were performed to produce ICP changes, and minimally invasive ICP and direct Codman intraparenchymal ICP were simultaneously acquired in six animals. The similarity between the invasive and minimally invasive methods in response to ICP increase was assessed using Pearson's correlation coefficient. It demonstrated good agreement between the two measures < r > = 0.8 ± 0.2, with a range of 0.31-0.99.
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http://dx.doi.org/10.1007/978-3-319-22533-3_19DOI Listing
July 2017

Validation of a New Noninvasive Intracranial Pressure Monitoring Method by Direct Comparison with an Invasive Technique.

Acta Neurochir Suppl 2016 ;122:93-6

University of São Paulo, São Paulo, Brazil.

The search for a completely noninvasive intracranial pressure (ICPni) monitoring technique capable of real-time digitalized monitoring is the Holy Grail of brain research. If available, it may facilitate many fundamental questions within the range of ample applications in neurosurgery, neurosciences and translational medicine, from pharmaceutical clinical trials, exercise physiology, and space applications. In this work we compare invasive measurements with noninvasive measurements obtained using the proposed new noninvasive method. Saline was infused into the spinal channel of seven rats to produce ICP changes and the simultaneous acquisition of both methods was performed. The similarity in the invasive and noninvasive methods of ICP monitoring was calculated using Pearson's correlation coefficients (r). Good agreement between measures < r > = 0.8 ± 0.2 with a range 0.28-0.96 was shown.
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http://dx.doi.org/10.1007/978-3-319-22533-3_18DOI Listing
July 2017

Ventricular-subcutaneous shunt for the treatment of experimental hydrocephalus in young rats: technical note.

Childs Nerv Syst 2016 Aug 23;32(8):1507-11. Epub 2016 Feb 23.

Division of Pediatric Neurosurgery, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Campus Universitário, Ribeirão Preto, SP, 14049-900, Brazil.

Background: Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools.

Objective: The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats.

Methods: We developed a ventricular-subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion.

Results: Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals.

Conclusions: An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus.
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http://dx.doi.org/10.1007/s00381-016-3042-1DOI Listing
August 2016

Pre- and postshunting magnetization transfer ratios are in accordance with neurological and behavioral changes in hydrocephalic immature rats.

Dev Neurosci 2014 18;36(6):520-31. Epub 2014 Oct 18.

Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, Brazil.

Hydrocephalus is a common neurological condition in children characterized by an imbalance between the production and absorption of cerebrospinal fluid (CSF), causing abnormal fluid accumulation in the brain cavities. Shunt systems have been used to drain excess CSF and to prevent progressive ventricular enlargement. However, despite improvements in these systems, neurological and structural changes cannot always be reversed. Our aim was to evaluate the magnetization transfer ratio as a biomarker for the effectiveness of a CSF shunt system to treat neurological and behavioral disorders observed in experimental hydrocephalus. Seven-day-old Wistar rats were used in this study. The pups were subjected to hydrocephalus induction via 20% kaolin intracisternal injection. After confirmation of ventriculomegaly by magnetic resonance imaging (MRI), a group of animals underwent placement of a ventriculosubcutaneous shunt (VSS). The reduction in ventricular size in hydrocephalic rats operated with functional VSS was observed as a decrease in ventricular ratio values and preservation of the corpus callosum thickness. Magnetization transfer values were significantly increased and matched to the recovery process of axonal myelination observed based on more-intense blue staining by solochrome cyanin. The histopathological analysis revealed a reduction in reactive astrocytes by means of GFAP immunostaining. The hydrocephalic rats operated with functional VSS also showed significant progress in motor and exploratory activities, similar to the control animals, at the end of the experiment. In conclusion, the VSS system employed 7 days after hydrocephalus induction was able to prevent structural damage and restore the axonal myelination process in periventricular structures by stabilizing and reducing the ventricular enlargement, and the results are in accordance with the magnetization transfer ratio in MRI.
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http://dx.doi.org/10.1159/000366056DOI Listing
July 2015

Morphometric analysis of the optic nerve in experimental hydrocephalus-induced rats.

Pediatr Neurosurg 2011 9;47(5):342-8. Epub 2012 May 9.

Department of Surgery and Anatomy, University of Sao Paulo, Ribeirao Preto, Brazil. betina77 @ gmail.com

Purpose: It was the aim of this study to investigate changes caused to the optic nerve of rats submitted to experimental hydrocephalus through morphometric analysis.

Method: At postnatal day 7, the rats underwent injection of kaolin into the cisterna magna, were sacrificed at postnatal day 14, 21 or 28, and the right optic nerves were dissected. We analyzed the area, minor diameter, densities of oligodendrocytes and astrocytes, total and damaged fibers as well as the relationship between damaged and total fibers.

Results: At postnatal day 14, there was a reduction in the density of astrocytes and damaged fibers when compared to the controls. At postnatal day 21, the area and the minor diameter were reduced compared to the controls, and the densities of oligodendrocytes and damaged fibers were increased compared to the controls. At postnatal day 28, there was a reduction in the area and the minor diameter and an increase in the densities of oligodendrocytes, astrocytes and damaged fibers when compared to controls.

Conclusion: The optic nerve of rats submitted to experimental hydrocephalus suffers morphometric changes.
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http://dx.doi.org/10.1159/000337728DOI Listing
December 2012

Cerebral white matter oxidation and nitrosylation in young rodents with kaolin-induced hydrocephalus.

J Neuropathol Exp Neurol 2012 Apr;71(4):274-88

Department of Pathology, University of Manitoba, Winnipeg, Canada.

Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities of the antioxidant enzymes catalase and glutathione peroxidase were not increased, and altered hypoxia-inducible factor 1α was not detected by quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.
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http://dx.doi.org/10.1097/NEN.0b013e31824c1b44DOI Listing
April 2012

Changes caused by hydrocephalus, induced by kaolin, in the corpus callosum of adult dogs.

Acta Cir Bras 2011 ;26 Suppl 2:8-14

Department of Surgery and Anatomy, FMRP, USP, Ribeirao Preto, Sao Paulo, Brazil.

Purpose: To analyze the ventricular enlargement and myelination of the corpus callosum in adult dogs after four and eight weeks of kaolin-induction of hydrocephalus.

Methods: 36 dogs were randomly divided into 3 groups: 1 - without hydrocephalus, 2 - kaolin-induction of hydrocephalus until the fourth week, and 3 - kaolin-induction of hydrocephalus until the eighth week. Ventricular ratios and volumes were calculated using magnetic resonance images, and myelination of the corpus callosum were histologically evaluated using solocromo-cianin stain.

Results: Radiological hydrocephalus was observed in 93.75% and overall mortality was 38.4%. Ventricular volumes and ratios were higher in groups 2 and 3 compared to group 1 and similar when measures in the fourth and eighth weeks were compared in the group 3. Indices of luminescence in the knee and in the splenium of the corpus callosum were higher in group 2 than in group 1 indicating that there was loss of myelin in group 2, and similar in groups 1 and 3, showing a tendency to remyelination after 8 weeks.

Conclusion: The corpus callosum of dogs with kaolin-induced hydrocephalus responds with demyelination of the knee and splenium by the fourth week with a tendency to remyelination by the eighth week.
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http://dx.doi.org/10.1590/s0102-86502011000800003DOI Listing
June 2012
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