Publications by authors named "Yasushi Takagi"

273 Publications

Single-session hematoma removal and transcortical venous approach for coil embolization of an isolated transverse-sigmoid sinus dural arteriovenous fistula in a hybrid operating room: illustrative case.

J Neurosurg Case Lessons 2022 May 23;3(21):CASE2267. Epub 2022 May 23.

Departments of Neurosurgery.

Background: Dural arteriovenous fistula (DAVF) can present with massive hematoma, which sometimes requires emergent removal. Therefore, a surgical strategy for single-session hematoma removal and shunt occlusion in the same surgical field is important.

Observations: A 73-year-old man was transferred to the authors' hospital with a headache. Brain computed tomography (CT) revealed an intracerebral hematoma in the right temporoparietal lobe (hematoma volume 12 ml). A cerebral angiogram revealed a right isolated transverse-sigmoid sinus (TSS)-DAVF fed by the occipital artery and middle meningeal artery. There was cortical venous reflux into the Labbé vein and posterior parietal vein. Percutaneous transarterial and transvenous embolization were unsuccessful. The following day, his consciousness level acutely declined with a headache, and brain CT showed hematoma expansion (hematoma volume 41 ml) with a midline shift. Therefore, the authors performed single-session hematoma removal and a transcortical venous approach for coil embolization of an isolated TSS-DAVF in a hybrid operating room. His postoperative course was uneventful. No recurrence was observed 3 months postoperatively on cerebral angiography.

Lessons: Single-session hematoma removal and a transcortical venous approach for coil embolization of an isolated TSS-DAVF is considered in cases with massive hematoma. This strategy is useful, considering recent developments in hybrid operating rooms.
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http://dx.doi.org/10.3171/CASE2267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204917PMC
May 2022

Efficacy of intraarterial indocyanine green videoangiography in surgery for arteriovenous fistula at the craniocervical junction in a hybrid operating room: illustrative cases.

J Neurosurg Case Lessons 2022 Jun 6;3(23):CASE22100. Epub 2022 Jun 6.

Department of Neurosurgery, Tokushima University, Tokushima, Japan.

Background: Sufficient understanding of the angioarchitecture of an arteriovenous fistula (AVF) at the craniocervical junction (CCJ) is crucial to surgical treatment but is often difficult because of the complex vascular anatomy. Intraarterial indocyanine green (ICG) videoangiography has emerged as a more useful option for understanding the vascular anatomy than intravenous ICG videoangiography. This report describes two cases of CCJ AVFs successfully treated by surgery using intraarterial ICG videoangiography and describes the efficacy of this technique.

Observations: Case 1 involved a 71-year-old man presenting with tetraparesis after sudden onset of severe headache due to subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) demonstrated CCJ epidural AVF. Intraarterial ICG videoangiography revealed the drainer, which had been difficult to identify. The AVF disappeared after disconnection of the drainer. Case 2 involved a 68-year-old man presenting with severe headache due to SAH. DSA showed multiple AVFs at the CCJ and cerebellar tentorium. Intraarterial ICG videoangiography demonstrated concomitant perimedullary AVF and dural AVF at the CCJ. All AVFs disappeared postoperatively.

Lessons: Intraarterial ICG videoangiography was useful for definitive diagnosis of CCJ AVF, facilitating identification of feeders and drainers with bright and high phase contrast and allowing repeated testing to confirm flow direction.
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http://dx.doi.org/10.3171/CASE22100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204929PMC
June 2022

An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture.

J Neuroinflammation 2022 Jun 20;19(1):161. Epub 2022 Jun 20.

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Kuramoto-cho, Tokushima, 770-8503, Japan.

Background And Purpose: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na/K-ATPase (ATP1α3).

Methods: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet.

Results: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05).

Conclusions: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.
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http://dx.doi.org/10.1186/s12974-022-02526-7DOI Listing
June 2022

Activation of the NLRP3/IL-1β/MMP-9 pathway and intracranial aneurysm rupture associated with the depletion of ERα and Sirt1 in oophorectomized rats.

J Neurosurg 2022 May 20:1-8. Epub 2022 May 20.

Objective: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm (IA) rupture is often a devastating event. Since the incidence of SAH increases especially in menopause, it is crucial to clarify the detailed pathogenesis of these events. The activation of vascular nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes has been studied in ischemic stroke and cardiovascular disease. However, the role of NLRP3 in IA rupture still needs to be explained. The authors sought to test their hypothesis that, under estrogen-deficient conditions, activation of NLRP3 inflammasomes via downregulation of the estrogen receptor (ER) facilitates IA rupture.

Methods: Ten-week-old female Sprague Dawley rats with and without oophorectomy were subjected to hemodynamic changes and hypertension (OVX+/HT and OVX-/HT, respectively) and fed a high-salt diet. Separately, using human brain endothelial cells (HBECs) and human brain smooth muscle cells (HBSMCs), the authors tested the effect of NLRP3 under estrogen-free conditions and in the presence of estradiol or of ER agonists.

Results: In OVX+/HT rats, the frequency of IA rupture was significantly higher than in OVX-/HT rats (p = 0.03). In the left posterior cerebral artery prone to rupture in OVX+/HT rats, the levels of the mRNAs encoding ERα and Sirt1, but not of that encoding ERβ, were decreased, and the levels of the mRNAs encoding NLRP3, interleukin-1β (IL-1β), and matrix metalloproteinase 9 (MMP-9) were elevated. Immunohistochemical analysis demonstrated that the expression profiles of these proteins correlated with their mRNA levels. Treatment with an ER modulator, bazedoxifene, normalized the expression profiles of these proteins and improved SAH-free survival. In HBECs and HBSMCs under estrogen-free conditions, the depletion of ERα and Sirt1 and the accumulation of NLRP3 were counteracted by exposure to estradiol or to an ERα agonist but not to an ERβ agonist.

Conclusions: To the authors' knowledge, this work represents the first demonstration that, in an aneurysm model under estrogen-deficient conditions, the depletion of ERα and Sirt1 may contribute to activation of the NLRP3/IL-1β/MMP-9 pathway, facilitating the rupture of IAs in the estrogen-deficient rat IA rupture model.
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http://dx.doi.org/10.3171/2022.4.JNS212945DOI Listing
May 2022

Thrombosed stuck mitral valve during advanced mechanical circulatory support for post-cardiotomy shock.

J Cardiol Cases 2022 May 16;25(5):282-284. Epub 2021 Dec 16.

Department of Cardiovascular Surgery, Fujita Health University School of Medicine, Toyoake, Japan.

We report a case of mechanical prosthetic mitral valve thrombosis in a 52-year-old woman with previous diagnosis of dilated cardiomyopathy, who was supported with advanced mechanical circulatory support after urgent mechanical mitral valve replacement (MVR) and tricuspid annuloplasty. Difficult weaning from cardiopulmonary bypass needed support with veno-arterial extracorporeal membranous oxygenation and Impella (Abiomed Inc, Danvers, MA, USA), so-called ECPELLA. Temporary discontinuation of heparin and massive blood transfusion were necessary due to four times of reoperation for bleeding during ECPELLA support. Poor recovery of cardiac function needed escalation from ECPELLA to extracorporeal biventricular assist device (ex-BiVAD) using two centrifugal pumps on Day 12. After gradual decrease in the left ventricular assist device flow, transesophageal echocardiography and fluoroscopic images revealed the stuck leaflets of the mitral prosthesis. Therefore, the patient underwent re-MVR with a bioprosthesis on Day 18, followed by continued assistance with ex-BiVAD. The patient was finally weaned from ex-BiVAD on Day 28 and was transferred to the referral hospital for rehabilitation. She was alive in good general condition at 2-year follow-up. It is important to balance the effects of anticoagulation on advanced mechanical circulatory support with ECPELLA, against the side effects of bleeding, especially in post-cardiotomy patients with bleeding tendency. < We should recognize the fatal risks of bleeding and thrombosis during advanced mechanical support, including Impella, VA-ECMO, ECPELLA, and ex-BiVAD, especially in the post-cardiotomy setting. We should also understand the choice of mechanical circulatory support, timely escalation to ex-BiVAD to avoid multiorgan failure, the diagnosis of mechanical mitral prosthetic thrombosed valve using echocardiography and fluoroscopy, and mitral valve replacement in the patient supported with ex-BiVAD.>.
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http://dx.doi.org/10.1016/j.jccase.2021.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091497PMC
May 2022

Effects of Cardiopulmonary Bypass on IgG Antibody Titers after SARS-CoV2 Vaccination.

Interact Cardiovasc Thorac Surg 2022 May 6. Epub 2022 May 6.

Department of Cardiovascular Surgery, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

Background: Patients with cardiovascular disease are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Although SARS-CoV2 vaccination may be effective, its impact on surgical patients is not well studied. We investigated the effects of cardiovascular surgery, especially under cardiopulmonary bypass (CPB), on the antibody titers after SARS-CoV2 vaccination.

Methods: A prospective observational study was designed for patients undergoing surgery between July to November 2021. The IgG against the receptor binding domain (RBD-IgG) was measured and antibody preserved rate (APR) was calculated from perioperative titers comparison.

Results: Enrolled 63 study patients were divided into 39 undergoing surgery with CPB (Group CPB) and 24 without CPB (Group None). Preoperative vaccines were BNT162b2 (Pfizer/BioNTech) (n = 58, 92%) and mRNA-1273 (Moderna) (n = 5, 8%). While RBD-IgG titers did not significantly decrease after surgery in Group None, they decreased significantly in Group CPB from 21.80 [11.15, 37.85] U/ml to 11.95 [6.80, 18.18] U/ml (p < 0.001) a day after surgery, 11.40 [7.85, 22.65] U/ml (p < 0.001) 14 days after surgery, and 7.60 [4.80, 17.60] U/ml (p < 0.001) a month after surgery, respectively. The APRs a day after the surgery were significantly lower in in Group CPB (0.46 [0.41, 0.60]) than in Group None (0.80 [0.68, 0.87]) (p < 0.001).

Conclusions: The SARS-CoV2 antibody titers significantly decreased with lower APRs immediately after surgery under CPB. Based upon our informative results, careful considerations of vaccination schedule might be required for surgery under CPB.

Clinical Registration Number: Fujita Health University Ethics Committee (HM 21-164).
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http://dx.doi.org/10.1093/icvts/ivac123DOI Listing
May 2022

A Novel Approach to Microvascular Decompression for Hemifacial Spasm: Method Description and Associated Outcomes.

Oper Neurosurg (Hagerstown) 2022 Jul 29;23(1):e16-e22. Epub 2022 Apr 29.

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Background: Microvascular decompression (MVD) is the only potential cure for hemifacial spasm (HFS). However, traditional techniques such as the interposition method may have limited effect in some cases. Alternative techniques have been proposed; however, they can be more complex or difficult to perform than the standard approach.

Objective: To describe a safe decompression technique-the "shelter method"-which involves creating a shelter-like space around the facial nerve root exit zone and present associated outcomes.

Methods: Medical records and intraoperative findings of 92 patients with HFS who underwent MVD using the shelter method between April 1997 and March 2017 were retrospectively reviewed. As a historical control group, we included 53 patients who had undergone MVD by the traditional interposition method before March 1989. The patients were divided into 3 subgroups according to the arteries involved and degree or direction of arterial compression to the seventh nerve. Patient outcomes were assessed as excellent, good, fair, and poor according to the MVD scoring system of the Japan Society for MVD Surgery.

Results: In the shelter method group, complete disappearance of HFS was achieved in 87 patients (94.6%). The curative rate of the shelter method group was significantly higher than that of the interposition method group. The overall complication rates were significantly lower in the shelter method group than in the interposition method group.

Conclusion: Our findings indicate high curative and low complication rates of the shelter method, suggesting that it helps treat HFS caused by various types of arterial compression.
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http://dx.doi.org/10.1227/ons.0000000000000223DOI Listing
July 2022

Development of a Navigation-guided Fence-post Catheter for Brain Tumor Resection.

J Med Invest 2022 ;69(1.2):117-119

Department of Neurosurgery, Tokushima University Faculty of Medicine, Tokushima, Japan.

Background: Navigation system devices have been developed to allow precise resection of brain tumor. The fence-post catheter techniques that use a navigation system have been used in many neurosurgery centers. However, an exclusive catheter for the fence-post catheter techniques have not been made, and substituted silicon tube of the cerebral ventricle drainage or a Nelaton catheter is widely used.

Objective: In this brief technical note, we describe a new fence-post catheter with steel tip device that was designed for more precise tissue resection and is useful in tumor resection.

Methods: The newly designed fence-post catheter helps to visually gauge the accurate depth from the tumor bottom during tumor resection. Furthermore, the catheter tip has moderate weight and is made of a non-magnetic material.

Results: Using our fence-post catheter, which has a metal part at the tip of the tube (length, 13 mm), operators can clearly notice that they are getting closer to base of the tumor by checking the metal part during the resection of deep tumors.

Conclusion: Our newly developed fence-post tube enables easy confirmation of the distance to deep-tissue regions and improves the degree of safety during tumor removal. J. Med. Invest. 69 : 117-119, February, 2022.
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http://dx.doi.org/10.2152/jmi.69.117DOI Listing
April 2022

Therapeutic Devices for Motor Symptoms in Parkinson's Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials.

Front Aging Neurosci 2022 29;14:807909. Epub 2022 Mar 29.

Department of Advanced Brain Research, Institute of Biomedical Sciences, Graduate School of Medicine, Tokushima University, Tokushima, Japan.

Background: Pharmacotherapy is the first-line treatment option for Parkinson's disease, and levodopa is considered the most effective drug for managing motor symptoms. However, side effects such as motor fluctuation and dyskinesia have been associated with levodopa treatment. For these conditions, alternative therapies, including invasive and non-invasive medical devices, may be helpful. This review sheds light on current progress in the development of devices to alleviate motor symptoms in Parkinson's disease.

Methods: We first conducted a narrative literature review to obtain an overview of current invasive and non-invasive medical devices and thereafter performed a systematic review of recent randomized controlled trials (RCTs) of these devices.

Results: Our review revealed different characteristics of each device and their effectiveness for motor symptoms. Although invasive medical devices are usually highly effective, surgical procedures can be burdensome for patients and have serious side effects. In contrast, non-pharmacological/non-surgical devices have fewer complications. RCTs of non-invasive devices, especially non-invasive brain stimulation and mechanical peripheral stimulation devices, have proven effectiveness on motor symptoms. Nearly no non-invasive devices have yet received Food and Drug Administration certification or a CE mark.

Conclusion: Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.
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http://dx.doi.org/10.3389/fnagi.2022.807909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020378PMC
March 2022

Japan Stroke Society Guideline 2021 for the Treatment of Stroke.

Int J Stroke 2022 Apr 20:17474930221090347. Epub 2022 Apr 20.

Department of Rehabilitation Medicine, School of Medicine, International University of Health and Welfare, Chiba, Japan.

The revised Japan Stroke Society Guidelines for the Treatment of Stroke were published in Japanese in July 2021. In this article, the extracted recommendation statements are published. The revision keeps pace with the great progress in stroke control based on the recently enacted Basic Act on Stroke and Cardiovascular Disease in Japan. The guideline covers the following areas: primary prevention, general acute management of stroke, ischemic stroke and transient ischemic attack, intracerebral hemorrhage, subarachnoid hemorrhage, asymptomatic cerebrovascular disease, other cerebrovascular disease, and rehabilitation.
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http://dx.doi.org/10.1177/17474930221090347DOI Listing
April 2022

Impact of supra-aortic vessel dissection on the neurological outcome in surgery for acute type A aortic dissection.

Heart Vessels 2022 Apr 16. Epub 2022 Apr 16.

Department of Cardiovascular Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan.

We investigated whether supra-aortic vessel (SAV)s dissection is a risk factor for neurological dysfunction (ND) after surgical repair for type A acute aortic dissection (TAAAD). A retrospective review was done in 178 patients with TAAAD undergoing aortic repair between 2015 and 2019, comparing those with SAV dissection to those without it. Preoperatively, 93 patients (54.4%) had SAV dissection. Postoperatively, ND occurred in 26 patients (14.6%), 17 of whom (65.4%) already had been present with preoperative ND. Patients with SAV dissection were more likely to have postoperative ND than those without it (21.5% vs 7.7%; p = 0.02). The severity of preoperative dissection-related stenosis in common carotid artery significantly related to postoperative ND (right; p =0.0071, left; p < 0.0001). Multivariable analysis showed dissection-related stenosis of > 75% in brachiocepharic and left common carotid arteries, and thrombosed false lumen in common carotid arteries were independent risk factors for postoperative ND. However, SAV dissection was not related to new onset of ND. Dissection with stenosis of > 75% in SAVs were significantly decreased after aortic repair and even after ascending aorta/hemiarch replacement. In conclusion, ND after surgical repair for TAAAD is closely related to SAV dissection, especially to stenosis of > 75% and thrombosed false lumen in common carotid arteries. Aortic repair significantly decreased SAV dissection and severity of stenosis.
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http://dx.doi.org/10.1007/s00380-022-02065-4DOI Listing
April 2022

Seizure types associated with negative arterial spin labeling and positive diffusion-weighted imaging on peri-ictal magnetic resonance imaging.

J Neurol Sci 2022 05 7;436:120223. Epub 2022 Mar 7.

Department of Neurosurgery, Graduate School of Biomedical Sciences, University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Tokushima, Japan.

Purpose: Arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures.

Methods: Overall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment.

Results: Of the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028).

Conclusion: A diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity.
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http://dx.doi.org/10.1016/j.jns.2022.120223DOI Listing
May 2022

The claw sign predicts first-pass effect in mechanical thrombectomy for cerebral large vessel occlusion in the anterior circulation.

Surg Neurol Int 2022 25;13:72. Epub 2022 Feb 25.

Departments of Clinical Neuroscience, Tokushima University, Tokushima, Japan.

Background: Mechanical thrombectomy (MT) is an effective treatment for acute cerebral large vessel occlusion (LVO). Complete recanalization of vessels in a single procedure is defined as the first-pass effect (FPE) and is associated with good prognosis. In this study, angiographic clot protruding sign termed the "claw sign," was examined as candidate preoperative imaging factor for predicting the FPE.

Methods: We retrospectively analyzed data from 91 consecutive patients treated for acute LVO in the anterior circulation by MT between January 2014 and December 2019. The claw sign was defined as a thrombus that protruded proximally by more than half of the diameter of the parent artery. Radiological findings such as claw sign, clinical and etiological features, and outcomes were compared between groups with and without successful FPE. Multivariate analysis was conducted to evaluate perioperative factors associated with FPE.

Results: FPE was achieved in 26 of 91 (28.6%) patients and the claw sign was observed in 34 of 91 (37.4%) patients. The claw sign was significantly more frequent in the successful FPE group than in the failed FPE group (53.8% vs. 30.8%; = 0.040). After the multivariate analysis, the claw sign was the only pretreatment parameter that could predict FPE (odds ratio, 2.67; 95% confidence interval, 1.01-7.06; = 0.047).

Conclusion: The claw sign is an angiographic imaging factor that might predict FPE after MT for anterior circulation acute ischemic stroke.
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http://dx.doi.org/10.25259/SNI_1160_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888293PMC
February 2022

Hybrid repair for Kommerell's diverticulum and right aortic arch with aberrant right vertebral artery.

Fujita Med J 2022 Feb 20;8(1):34-36. Epub 2021 Mar 20.

Department of Cardiovascular Surgery, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan.

Kommerell's diverticulum (KD) is a rare aneurysm of the origin of an aberrant subclavian artery. Hybrid aortic arch repair for KD is being performed more often. We report hybrid arch repair for KD in a 63-year-old man with a right aortic arch and aberrant right vertebral artery, an extremely rare variant. We performed total arch replacement to completely reconstruct the five cervical arteries with elephant trunk to create an adequate landing zone, followed by second-stage endovascular stent-grafting from the ascending aorta to the proximal descending aorta.
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http://dx.doi.org/10.20407/fmj.2020-016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874913PMC
February 2022

Intravenous Alteplase at 0.6 mg/kg for Unknown Onset Stroke with Prior Antithrombotic Medication: THAWS Randomized Clinical Trial.

J Atheroscler Thromb 2022 Feb 24. Epub 2022 Feb 24.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.

Aim: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke.

Methods: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well >4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication.

Results: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p<0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p<0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication.

Conclusion: Alteplase appears more beneficial in patients with prior antithrombotic medication.
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http://dx.doi.org/10.5551/jat.63337DOI Listing
February 2022

[Arteriovenous Malformations(AVM)].

Authors:
Yasushi Takagi

No Shinkei Geka 2022 Jan;50(1):196-204

Department of Neurosurgery, Tokushima University Graduate School of Medical Sciences.

Recently, a KRAS mutation located in the endothelial cells of the nidus in arteriovenous malformations(AVMs)was reported. The findings indicate the possibility of medical therapy against cerebral AVMs; the blockade of RAS-MAPK signaling cascade may stabilize AVM nidus. As for surgical treatment for AVMs, achievement of low morbidity is the most important objective. To achieve this, assessment of blood flow, usage of non-stick bipolar forceps, and 3D simulation prior to operation are important. Assessment of individual cases for surgical treatment leads to low morbidity in surgeries.
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http://dx.doi.org/10.11477/mf.1436204544DOI Listing
January 2022

Gelatin-thrombin Hemostatic Matrix-related Cyst Formation after Cerebral Hematoma Evacuation: A Report of Two Cases.

NMC Case Rep J 2021 23;8(1):719-725. Epub 2021 Oct 23.

Department of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Tokushima, Japan.

The gelatin-thrombin matrix, Floseal, is an excellent novel hemostatic agent that is used in various surgical fields. Thrombin is a serine protease, and the conversion of prothrombin to thrombin is an essential step in the coagulation cascade. However, thrombin can induce blood-brain barrier (BBB) disruption and vasogenic brain edema. This report describes two cases of gelatin-thrombin matrix-related cyst formation after cerebral hematoma evacuation. An 82-year-old man with a gelatin-thrombin matrix-related cyst was treated by cyst drainage and fenestration to the lateral ventricle. Histological evaluation of the cyst wall showed a gelatin-thrombin matrix reserve, marked infiltration of inflammatory cells, and foam cell accumulation. In addition, an 85-year-old woman with a gelatin-thrombin matrix-related cyst was treated with steroids and responded well. In both cases, the post-treatment course was uneventful. Cyst shrinkage and no recurrence were observed. The gelatin-thrombin matrix can cause cyst formation with brain edema. This is the first report demonstrating the cyst wall pathology and the steroid responsivity on cyst shrinkage. The mechanism of cyst formation is thought to be thrombin-induced BBB disruption. Excess gelatin-thrombin matrix should be carefully removed from the surgical beds, particularly those having a blinded space from the neurosurgical microscope.
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http://dx.doi.org/10.2176/nmccrj.cr.2021-0130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769470PMC
October 2021

Efficacy of Intra-arterial Indocyanine Green Videoangiography in Hemangioblastoma Surgery: A Case Report.

NMC Case Rep J 2021 3;8(1):295-300. Epub 2021 Jul 3.

Department of Neurosurgery, Tokushima University Hospital, Tokushima, Tokushima, Japan.

Intravenous indocyanine green (ICG) videoangiography is reportedly useful for vascular neurosurgery, and for treating hemangioblastoma due to its high vascularity. Videoangiography obtained after intra-arterial ICG injection has emerged as a more useful option than that after intravenous injection. This report offers the first description of a case of hemangioblastoma successfully treated using intra-arterial ICG videoangiography, and describes the efficacy of this technique. A 20-year-old man presented with progressive cerebellar ataxia and dysphagia. Magnetic resonance imaging (MRI) revealed an enhanced solid tumor in the medulla oblongata. Digital subtraction angiography (DSA) showed a highly vascularized tumor. Surgery was performed to remove the tumor in a hybrid operating room. A catheter was introduced into the vertebral artery (VA) for intra-arterial ICG videoangiography. Superficial feeders and drainers were identified and flow dynamic changes in the tumor were assessed by intra-arterial ICG videoangiography. The tumor was removed after confirming lack of flow in the drainer. Intra-arterial ICG videoangiography was more useful than intravenous ICG videoangiography in hemangioblastoma surgery for identifying feeders and drainers and assessing flow dynamics in the tumor. Use of Flow 800 made these findings simpler and easier to evaluate.
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http://dx.doi.org/10.2176/nmccrj.cr.2020-0281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8769404PMC
July 2021

Chronic subdural hematoma associated with dural metastasis leads to early recurrence and death: A single-institute, retrospective cohort study.

J Clin Neurosci 2021 Dec 8;94:244-249. Epub 2021 Nov 8.

Department of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

The prevalence of chronic subdural hematoma (CSDH) associated with dural metastasis is uncertain, and appropriate treatment strategies have not been established. This study aimed to investigate the characteristics of and appropriate treatment strategies for CSDH associated with dural metastasis. We retrospectively reviewed the charts of 214 patients who underwent surgery for CSDH. The patients were divided into the dural metastasis group (DMG; n = 5, 2.3%) and no dural metastasis group (No-DMG; n = 209, 97.3%). Patient characteristics, treatment, and outcomes were compared between the two groups. Active cancer was detected in 31 out of 214 patients, 5 of whom (16.1%) had dural metastasis. In-hospital death (80.0% vs. 0%; p < 0.001) and recurrence within 14 days (80.0% vs. 2.9%; p < 0.001) and 60 days (80.0% vs. 13.9%; p = 0.002) were significantly prevalent in the DMG. All patients in the DMG developed subdural hematoma re-accumulation requiring emergent surgery because of brain herniation, and patients in the DMG had significantly worse recurrence-free survival (p < 0.001). This relationship remained significant (p < 0.001) even when the analysis was limited to the active cancer cohort (n = 31). CSDH associated with dural metastasis leads to early recurrence and death because of the difficulty in controlling subdural hematoma re-accumulation by common drainage procedures. Depending on the primary cancer status, withdrawal of active treatment and change to palliative care should be discussed after diagnosing CSDH associated with dural metastasis.
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http://dx.doi.org/10.1016/j.jocn.2021.10.037DOI Listing
December 2021

[Mitral Valve Surgery for a Patient with Mediastinal Shift after Left Pneumonectomy:Report of a Case].

Kyobu Geka 2021 Nov;74(12):1008-1011

Department of Cardiovascular Surgery, Fujita Health University, Toyoake, Japan.

A 70-year-old patient who survived about 40 years after left pneumonectomy for tuberculosis visited emergency hospital, because of dyspnea. She received suitable medical therapy for atirial fibrillation and severe mitral regurgitation and hesitated heart surgery because of anxiety for surgical risk. The computed-tomography showed mediastinal shift to left and right lung compensatory expansion. Respiratory function test after treatment of heart failure showed only mild restrictive disorder. And the blood-gas examination in room air was 101 mmHg of Pao2 and 37 mmHg of Paco2. The mitral valve replacement was performed via median sternotomy and using normal cardiopulmonary bypass. And she fully recoverd without any respiratory complications. Mediastinal shift did not obstract the surgical view and establishment of cardiopulmonary bypass in this case. It seemed that the key of surgical successs is the preserved function of healthy residual lung.
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November 2021

Ataxia with vitamin E deficiency in the Philippines : A case report of two siblings.

J Med Invest 2021 ;68(3.4):400-403

Department of Neurology, Institute of Biomedical Sciences, Graduate School of Medicine, Tokushima University, Tokushima, Japan.

Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.
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http://dx.doi.org/10.2152/jmi.68.400DOI Listing
November 2021

Continued-Maintenance Therapy with High-dose Methotrexate Improves Overall Survival of Patients with Primary Central Nervous System Lymphoma.

J Med Invest 2021 ;68(3.4):286-291

Department of Neurosurgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan, Tokushima, 770-8503, Japan.

Background: PCNSL is mainly treated with HD-MTX-based chemotherapy with or without WBRT. However, As WBRT is associated with delayed neurotoxicity leading to dementia in the elderly, many institutes reported benefits of intensive chemotherapy or high-dose chemotherapy with ASCT. We investigated whether treatment with HD-MTX and rituximab, followed by continued-maintenance HD-MTX monotherapy (3.5g / m2), improves overall survival (OS).

Methods: In this retrospective, single-center trial 52 immunocompetent patients with newly diagnosed PCNSL were included. All were treated between January 2005 and December 2017. The controls were 18 patients who, between 2005 and 2011, had received 3 cycles of HD-MTX and then adjuvant treatment with WBRT. In 2011 we started HD-MTX continued-maintenance therapy to treat 34 PCNSL patients. In the induction phase, these patients received HD-MTX every 14 days until a complete response (CR) was observed. When CR was obtained, maintenance therapy with HD-MTX (3.5g / m2) was delivered every three months.

Results: In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT. J. Med. Invest. 68 : 286-291, August, 2021.
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http://dx.doi.org/10.2152/jmi.68.286DOI Listing
November 2021

Two-staged surgical treatment for Kommerell diverticulum with a right aortic arch and an aberrant left subclavian artery.

Gen Thorac Cardiovasc Surg 2022 Jan 4;70(1):83-86. Epub 2021 Oct 4.

Department of Cardiovascular Surgery, Fujita Health University, 1-98 Kutsukake-cho, Toyoake-shi, Aichi, 470-1192, Japan.

Kommerell diverticulum (KD) is an aneurysm of the orifice of an aberrant subclavian artery (SCA) from the descending aorta or aortic arch. We have performed two-staged surgical strategy for the treatment of KD with right aortic arch. The first step was the bypass grafting between the left common carotid artery and the aberrant left SCA with occlusion of the distal side of KD with the plug. The second step was the descending aorta replacement through the right thoracotomy. Four patients underwent these operations. No hospital deaths or major complications were observed. All four patients were discharged and have been alive for 1-6 years without any health problems. Two of four patients had symptoms of dysphagia preoperatively, and it resolved postoperatively in both patients. No hoarseness occurred after surgery, and 1-6 years of CT observation showed no recanalization of the vascular plug.
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http://dx.doi.org/10.1007/s11748-021-01715-0DOI Listing
January 2022

Effects of periodic robot rehabilitation using the Hybrid Assistive Limb for a year on gait function in chronic stroke patients.

J Clin Neurosci 2021 Oct 31;92:17-21. Epub 2021 Jul 31.

Rehabilitation Unit, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Using a robot for gait training in stroke patients has attracted attention for the last several decades. Previous studies reported positive effects of robot rehabilitation on gait function in the short term. However, the long-term effects of robot rehabilitation for stroke patients are still unclear. The purpose of the present study was to investigate the long-term effects of periodic gait training using the Hybrid Assistive Limb (HAL) on gait function in chronic stroke patients. Seven chronic stroke patients performed 8 gait training sessions using the HAL 3 times every few months. The maximal 10-m walk test and the 2-minute walking distance (2MWD) were measured before the first intervention and after the first, second, and third interventions. Gait speed, stride length, and cadence were calculated from the 10-m walk test. Repeated one-way analysis of variance showed a significant main effect on evaluation time of gait speed (F = 7.69, p < 0.01), 2MWD (F = 7.52, p < 0.01), stride length (F = 5.24, p < 0.01), and cadence (F = 8.43, p < 0.01). The effect sizes after the first, second, and third interventions compared to pre-intervention in gait speed (d = 0.39, 0.52, and 0.59) and 2MWD (d = 0.35, 0.46, and 0.57) showed a gradual improvement of gait function at every intervention. The results of the present study showed that gait function of chronic stroke patients improved over a year with periodic gait training using the HAL every few months.
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http://dx.doi.org/10.1016/j.jocn.2021.07.040DOI Listing
October 2021

Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group.

J Neurosurg 2022 04 10;136(4):1005-1014. Epub 2021 Sep 10.

1Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto.

Objective: Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression.

Methods: The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression.

Results: Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 67 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression.

Conclusions: These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.
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http://dx.doi.org/10.3171/2021.3.JNS203913DOI Listing
April 2022

Involvement of Neutrophil Extracellular Traps in Cerebral Arteriovenous Malformations.

World Neurosurg 2021 11 31;155:e630-e636. Epub 2021 Aug 31.

Department of Neurosurgery, Tokushima University Hospital, Tokushima, Tokushima, Japan.

Background: Cerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs.

Methods: We analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients.

Results: Expression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus.

Conclusions: Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs.
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http://dx.doi.org/10.1016/j.wneu.2021.08.118DOI Listing
November 2021

Dystonia and Cerebellum: From Bench to Bedside.

Life (Basel) 2021 Jul 31;11(8). Epub 2021 Jul 31.

Department of Advanced Brain Research, Institute of Biomedical Sciences, Graduate School of Medicine, Tokushima University, Tokushima 770-8501, Japan.

Dystonia pathogenesis remains unclear; however, findings from basic and clinical research suggest the importance of the interaction between the basal ganglia and cerebellum. After the discovery of disynaptic pathways between the two, much attention has been paid to the cerebellum. Basic research using various dystonia rodent models and clinical studies in dystonia patients continues to provide new pieces of knowledge regarding the role of the cerebellum in dystonia genesis. Herein, we review basic and clinical articles related to dystonia focusing on the cerebellum, and clarify the current understanding of the role of the cerebellum in dystonia pathogenesis. Given the recent evidence providing new hypotheses regarding dystonia pathogenesis, we discuss how the current evidence answers the unsolved clinical questions.
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http://dx.doi.org/10.3390/life11080776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401781PMC
July 2021

Coil embolization with overlapping horizontal low-profile stents to treat a giant thrombosed fetal posterior cerebral artery aneurysm using contralateral approach through anterior communicating artery: Case report.

Surg Neurol Int 2021 12;12:347. Epub 2021 Jul 12.

Department of Neurosurgery, Tokushima University, Tokushima, Japan.

Background: The treatment of internal carotid artery (ICA) - posterior communicating artery aneurysms (ICPC aneurysms) is challenging when a fetal posterior cerebral artery (PCA) arises from the saccular neck. This complex angioarchitecture renders endovascular approaches difficult. Giant thrombosed IC-PC aneurysms are also hard to treat by endovascular coiling because its flow-diversion effect is insufficient.

Case Description: We report the first case of a ruptured giant thrombosed IC-PC aneurysm associated with a fetal PCA that was successfully treated by coil embolization with retrograde overlap horizontal stenting using low-profile stents introduced through the contralateral ICA. The aneurysm was completely occluded and follow-up MRI scans demonstrated the reduction of the aneurysmal size.

Conclusion: Our technique is advantageous because low-profile stents can be used to treat lesions not accessible with flow-diverter stents due their presence in complex angioarchitectures, and overlap stenting may have flow-diversion effects that can result in the complete occlusion of giant thrombosed aneurysms.
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http://dx.doi.org/10.25259/SNI_533_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326112PMC
July 2021

Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway.

Sci Rep 2021 07 23;11(1):15105. Epub 2021 Jul 23.

Department of Neurosurgery, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.

Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.
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http://dx.doi.org/10.1038/s41598-021-93896-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302615PMC
July 2021

STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases.

Eur Heart J 2021 11;42(42):4336-4348

Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-Cho, Tokushima 770-8503, Japan.

Aims: Lifestyle-related diseases promote atherosclerosis, a chronic inflammatory disease; however, the molecular mechanism remains largely unknown. Endogenous DNA fragments released under over-nutrient condition provoke sterile inflammation through the recognition by DNA sensors. Here, we investigated the role of stimulator of interferon genes (STING), a cytosolic DNA sensor, in atherogenesis.

Methods And Results: Apolipoprotein E-deficient (Apoe-/-) mice fed a western-type diet (WTD), a hypercholesterolaemic mouse model, showed higher STING expression and markers for DNA damage such as γH2AX, p53, and single-stranded DNA (ssDNA) accumulation in macrophages in the aorta compared with wild-type (WT) mice. The level of cGAMP, a STING agonist, in the aorta was higher in Apoe-/- mice. Genetic deletion of Sting in Apoe-/- mice reduced atherosclerotic lesions in the aortic arch, lipid, and macrophage accumulation in plaques, and inflammatory molecule expression in the aorta compared with the control. Pharmacological blockade of STING using a specific inhibitor, C-176, ameliorated atherogenesis in Apoe-/- mice. In contrast, bone marrow-specific STING expression in Apoe-/- mice stimulated atherogenesis. Expression or deletion of STING did not affect metabolic parameters and blood pressure. In vitro studies revealed that STING activation by cGAMP or mitochondrial DNA accelerated inflammatory molecule expression (e.g. TNF-α or IFN-β) in mouse and human macrophages. Activation of nuclear factor-κB and TANK binding kinase 1 was involved in STING-associated vascular inflammation and macrophage activation. Furthermore, human atherosclerotic lesions in the carotid arteries expressed STING and cGAMP.

Conclusion: Stimulator of interferon genes stimulates pro-inflammatory activation of macrophages, leading to the development of atherosclerosis. Stimulator of interferon genes signalling may serve as a potential therapeutic target for atherosclerosis.
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http://dx.doi.org/10.1093/eurheartj/ehab249DOI Listing
November 2021
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