Explore the vast range of titles available.

Cell therapy for Parkinson’s disease (PD) began in 1979 with the transplantation of fetal rat dopamine-containing neurons that improved motor abnormalities in the PD rat model with good survival of grafts and axonal outgrowth. Thirty years have passed since the 2 clinical trials using cell transplantation for PD patients were first reported. Recently, cell therapy is expected to develop as a realistic treatment option for PD patients owing to the advancement of biotechnology represented by pluripotent stem cells. Medication using levodopa, surgery including deep brain stimulation, and rehabilitation have all been established as current therapeutic strategies. Strong therapeutic effects have been demonstrated by these treatment methods, but they have been unable to stop the progression of the disease. Fortunately, cell therapy might be a key for true neurorestoration. This review article describes the historical development of cell therapy for PD, the current status of cell therapy, and the future direction of this treatment method.

Microvascular decompression (MVD) has proven efficacy in trigeminal neuralgia (TN) and hemifacial spasm (HFS). This study utilized computational fluid dynamics (CFD) to investigate the impact of MVD on wall shear stress (WSS) of responsible arteries (RAs) at the neurovascular contact (NVC). A total of 21 cases (10 TN, 11 HFS) were analyzed, involving RAs at NVC validated through intraoperative photographs. Hemodynamic parameters (WSS, vessel diameter, flow rate, pressure drop) was calculated using CFD for the RAs based on 3D silent-magnetic resonance angiograms. The NVC was segmented into NVC-proximal, NVC-site, and NVC-distal portions using simulated 3D CFD images that correlated with surgical observations. WSS ratios of NVC-site to NVC-proximal (NVC-site/proximal) was calculated both before and after MVD. Prior to MVD, WSS in the RA at the NVC displayed a peaked curve with a maximum at NVC-site; however, post MVD, it presented a smooth curve without peaks. The WSS ratio exhibited a significant decrease after MVD. The impact of MVD on WSS of RAs at NVC was evaluated in both TN and HFS cases. Analyzing the hemodynamics of RAs through CFD and identifying WSS peaks at NVC portions before MVD provided a more detailed and localized understanding of the morphologically depicted NVC.

The mechanism of bleb formation in unruptured intracranial aneurysms (UIAs) remains unclear. This study aimed to investigate the association between peri-aneurysmal contact (PAC) and bleb formation. Forty-five aneurysms were classified depending on the presence of blebs and PAC using computed tomographic angiography and magnetic resonance imaging. Aneurysmal hemodynamics were assessed using computational fluid dynamics. The independent variables associated with bleb formation were statistically assessed. Fourteen aneurysms (31.1%) had blebs, all of which were located at the site of PAC (group A). Thirty-one aneurysms (68.9%) had no bleb, of which 13 had a PAC (group B) and 18 had no PAC (group C). PAC was the only independent variable associated with bleb formation ( p  < 0.05). Aneurysmal volumes were significantly higher in group A, followed by groups B and C in series. Aneurysmal wall shear stress (WSS) tended to be lowest in group A, followed by groups B and C in series. The maximum WSS at the blebs was only 17% of the maximum WSS at the aneurysmal domes. This study demonstrated that bleb formation in UIAs was associated with the establishment of PAC during their growth, which may have more detrimental effects on bleb formation than hemodynamics.

Despite advances in surgical and medical therapy, glioblastoma consistently remains a fatal disease. Over the last 20 years, no significant increase in survival has been achieved for patients with this disease. The formation of abnormal tumor vasculature and glioma cell invasion along white matter tracts are believed to be the major factors responsible for the resistance of these tumors to treatment. Therefore, investigation of angiogenesis and invasion in glioblastoma is essential for the development of a curative therapy. In our report, we first reviewed certain histopathological studies that focus on angiogenesis and invasion of human malignant gliomas. Second, we considered several animal models of glioma available for studying angiogenesis and invasion, including our novel animal models. Third, we focused on the molecular aspects of glioma angiogenesis and invasion, and the key mediators of these processes. Finally, we discussed the recent and ongoing clinical trials targeting tumor angiogenesis and invasion in glioma patients. A better understanding of the mechanism of glioma angiogenesis and invasion will lead to the development of new treatment methods.

Hydrogen peroxide (H 2 O 2 ) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H 2 O 2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H 2 O 2 on antitumor immunity remain unclear. To investigate the effects of H 2 O 2 , especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H 2 O 2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H 2 O 2 /RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H 2 O 2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor‐draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H 2 O 2 /RT combination group. In addition, analyses of tumor‐infiltrating lymphocytes showed that the number of CD8 + (cluster of differentiation 8) T cells and the frequency of IFN‐γ + (interferon gamma) CD8 + T cells were higher in the noninjected/nonirradiated tumors in the H 2 O 2 /RT group compared to those in the other groups. PD‐1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H 2 O 2 /RT group. Intratumoral injection of H 2 O 2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD‐1 blockade. These findings promote the development of H 2 O 2 /RT therapy combined with cancer immunotherapies, even for advanced cancers.

Purpose Arteriovenous fistulas (AVFs) located in the cavernous sinus (CS), clivus, and condyle can be osseous shunts in nature. Here, we reviewed the angioarchitecture, clinical characteristics, and treatment results of AVFs in these lesions. Methods Twenty-five patients with 27 lesions who underwent rotational angiography in our department between May 2013 and December 2019 were reviewed. We examined 20 CS AVFs, 2 clival AVFs, and 5 condylar AVFs. We divided the anatomical shunted pouches into five locations: the dorsum sellae (posteromedial of the CS), posterolateral wall of the CS, lateral wall of the CS, clivus, and condyle. We divided the AVFs into three categories: intraosseous, transitional, and nonosseous shunts. We analyzed the characteristics and treatment results. Results A total of 33 shunted pouches or points were identified in 27 lesions. The dorsum sellae ( n  = 16) was the most frequent location. Fourteen AVFs (88%) in the dorsum sellae were osseous (intraosseous or transitional) shunts. All AVFs in the clivus or condyle were also osseous shunts. Eleven lesions (92%) of intraosseous and all lesions of transitional shunts exhibited bilateral external carotid artery involvement as feeders. Ten lesions (83%) of intraosseous shunts were treated with selective transvenous embolization of the shunted pouch with or without additional partial embolization of the sinus. Eleven (92%) intraosseous shunts were completely occluded, and symptom resolution was achieved in all intraosseous shunts. Conclusion Most of the CS AVFs with shunted pouches in the dorsum sellae and all of the AVFs in the clivus and condyle share similar characteristics.

Abstract BACKGROUND Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. OBJECTIVE To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. METHODS We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. RESULTS There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. CONCLUSION In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients. Graphical Abstract Graphical Abstract

Intra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase. Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1 × 10(6) cells/ 1 ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48 h group) after MCAO. PBS (1 ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays. Behavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p's<0.05). Similarly, the infarct volumes of stroke rats in 24h group were much significantly decreased compared to those in all other groups (p's<0.05). These observed behavioral and histological effects were accompanied by MSC survival and migration, with the highest number of integrated MSCs detected in the 24h group. Moreover, bFGF and SDF-1α levels of the infarcted cortex were highly elevated in the 24h group compared to control group (p's<0.05). These results suggest that intra-arterial allogeneic transplantation of MSCs provides post-stroke functional recovery and reduction of infarct volumes in ischemic stroke model of rats. The upregulation of bFGF and SDF-1α likely played a key mechanistic role in enabling MSC to afford functional effects in stroke. MSC transplantation at 24 hours after recanalization appears to be the optimal timing for ischemic stroke model, which should guide the design of clinical trials of cell transplantation for stroke patients.

BackgroundHyponatremia generally occurs after transsphenoidal surgery (TSS) in a delayed fashion. Most patients with delayed postoperative hyponatremia (DPH) are asymptomatic or only express non-specific symptoms; consequently, DPH is associated with prolonged hospitalization. No consensus has been reached on which patients are at greatest risk of developing DPH. We reviewed patients with DPH and evaluated predictive factors for DPH.MethodsWe retrospectively analyzed 107 consecutive patients who underwent endoscopic TSS for pituitary adenoma (January 2010–December 2016). Patients with DPH (hyponatremia group) and without DPH (normonatremia group) were compared according to their nadir sodium levels on postoperative days 3 to 10. We documented the patients’ demographics, clinical features, and postoperative physiological characteristics.ResultsTwenty-five (23.4%) patients developed DPH after endoscopic TSS. The patients’ mean age was 54 ± 17 years, and 63.6% of the patients were female. The overall prevalence of DPH was 23.4%. The non-parametric χ2 test and the Mann–Whitney U test revealed statistically significant differences in age, use of antihypertensive drugs, nonfunctioning pituitary adenoma, and higher yet normal preoperative thyroid-stimulating hormone level between the hyponatremia and normonatremia groups (P < 0.05). Logistic regression analysis revealed that only older age was a useful independent predictive factor for DPH (odds ratio, 1.05; 95% confidence interval, 1.01–1.08; P = 0.01). The serum sodium levels on postoperative day 2 were significantly lower in the hyponatremia than normonatremia group (P < 0.01) and were negatively correlated with age (r = − 0.25, P < 0.05). The cut-off age for predicting DPH was 55 years. The hospital stay was significantly longer in the hyponatremia than normonatremia group (P < 0.01).ConclusionsAge of more than 55 years was an independent predictive factor for DPH even after adjusting for potential confounders. Older age was negatively correlated with the serum sodium level on postoperative day 2. Preventing early decreases in the sodium level could reduce the risk of DPH.Trial registration1707-027

Cell therapy for disorders of the central nervous system has progressed to a new level of clinical application. Various clinical studies are underway for Parkinson's disease, stroke, traumatic brain injury, and various other neurological diseases. Recent biotechnological developments in cell therapy have taken advantage of the technology of induced pluripotent stem (iPS) cells. The advent of iPS cells has provided a robust stem cell donor source for neurorestoration via transplantation. Additionally, iPS cells have served as a platform for the discovery of therapeutics drugs, allowing breakthroughs in our understanding of the pathology and treatment of neurological diseases. Despite these recent advances in iPS, adult tissue‐derived mesenchymal stem cells remain the widely used donor for cell transplantation. Mesenchymal stem cells are easily isolated and amplified toward the cells' unique trophic factor‐secretion property. In this review article, the milestone achievements of cell therapy for central nervous system disorders, with equal consideration on the present translational obstacles for clinic application, are described.