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The glymphatic system (GS) plays an important role in subarachnoid hemorrhage (SAH). Nimodipine treatment provides SAH patients with short-term neurological benefits. However, no trials have been conducted to quantify the relationship between nimodipine and GS. We hypothesized that nimodipine could attenuate early brain injury (EBI) after SAH by affecting the function of the GS. In this study, we assessed the effects of nimodipine, a dihydropyridine calcium channel antagonist, on mice 3 days after SAH. The functions of GS were assessed by immunofluorescence and western blot. The effects of nimodipine were assessed behaviorally. Concurrently, correlation analysis was performed for the functions of GS, immunofluorescence and behavioral function. Our results indicated that nimodipine improved GS function and attenuated neurological deficits and brain edema in mice with SAH. Activation of the cAMP/PKA pathway was involved in this process. GS function was closely associated with perivascular AQP4 polarization, cortical GFAP/AQP4 expression, brain edema and neurobehavioral function. In conclusion, this study shows for the first time that nimodipine plays a neuroprotective role in the period of EBI after SAH in mice through the GS.

Ubiquitin-specific protease 22 (USP22), a potential marker of cancer stem cells, significantly influences stem cell fate choices. However, its functions in neural stem cells (NSCs) and adult neurogenesis, especially following traumatic brain injury (TBI), remain only partially understood. Here, we found that aberrant USP22 expression could affect NSC proliferation and stemness maintenance, as assessed by the generation of neurospheres, cell counting kit-8 (CCK-8) and immunofluorescence staining in vitro. Moreover, USP22 depletion promotes the differentiation of NSCs, both in vitro and in vivo. In contrast, USP22 overexpression inhibits NSC differentiation into neurons. Interestingly, our data showed that USP22 promotes the proliferation but inhibits the differentiation of NSCs in the dentate gyrus (DG) of the hippocampus soon after TBI. The Morris water maze (MWM) test was adopted to evaluate neurological function, which confirmed that USP22 could improve the learning and memory capacity that was already compromised following TBI. Overall, this study uncovers a potentially novel regulatory role of USP22 in the proliferation and differentiation ability of NSCs, contributing to the hippocampus-dependent cognitive function of TBI mice and may be a novel target for future therapeutic approaches.

Xiaopeng Cui,1,2,* Wen-Qiang Xin,1,* Bangyue Wang,1 Yan Zhao,1 Changkai Hou,1 Shifei Cai,1 Chao Peng,1 Zhen Wang,1 Jian Li,1 Linchun Huan,3 Lei Chen,2 Xinyu Yang1 1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Neurosurgery, Tianjin Fifth Central Hospital, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Linyi People’s Hospital, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinyu YangDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Medical University, 154 Anshan Road, Peace Zone, Tianjin, 300041, People’s Republic of ChinaEmail yangxinyu@tmu.edu.cnLei ChenDepartment of Neurosurgery, Tianjin Fifth Central Hospital, 41 Zhejiang Road, Binhai New Area, Tianjin, 300450, People’s Republic of ChinaEmail chenlei1130@163.comObjective: Several studies have reported that single-nucleotide polymorphisms (SNPs) of the CDKN2A/CDKN2B gene on chromosome 9p21.3 are associated with increased risk of intracranial aneurysm (IA). However, the association between IAs and SNPs of CDKN2A/CDKN2B in Chinese Han people is yet to be evaluated. This study examined the association of the SNPs rs10811661 and rs4977574 with IA in the Chinese Han population.Methods: A total of 595 IA patients and 600 sex- and age-matched controls were enrolled in the study. Peripheral blood was collected and stored at – 80°C until use. CDKN2A/CDKN2B was identified using polymerase chain reaction–ligase detection reaction. SNP genotyping was performed for rs10811661 and rs4977574 using a MassArray system. Associations between these two SNPs and IAs was tested with χ2 or Fisher’s exact tests and multivariate logistic regression.Results: rs10811661 and rs4977574 were significantly associated with IA. The frequency of rs10811661-T in IA was higher than in controls (OR 1.26, 95% CI 1.07– 1.49; P< 0.01). There was no significant difference in frequency of haplotype between control subjects and IA patients.Conclusion: rs10811661 and rs4977574 on 9p21.3 were strongly associated with genetic susceptibility to IA in the Chinese Han population, which emphasizes a need for further investigation.Keywords: intracranial aneurysm, CDKN2A/CDKN2B gene, Chinese Han population, SNP

Background Unruptured extracranial vertebral artery (VA) aneurysms are uncommon and have rarely been described with treatment options. Here we report the successful reconstruction of an asymptomatic extracranial left VA aneurysm, highlighting the treatment for extracranial VA aneurysm and showing the superiority of a hybrid operating room in cerebral vascular diseases. Case Description In this 57-year-old female who had sustained an extracranial left VA aneurysm, magnetic resonance angiography showed bilateral VAs as codominant in the vertebrobasilar system. Digital subtraction angiography demonstrated that the fusiform aneurysm (18.7 × 15.4 mm) was present at the proximal part of the left VA. Aneurysm resection and vascular graft reconstruction were performed in the hybrid operating room. A successful outcome was noted at the 6-month follow-up. Conclusions Extracranial VA aneurysm in the V1 segment can be well treated with open surgery using a prosthetic graft. Preserving the function of the affected VA should always be a point of concern.

Background and purpose Blood that enters the subarachnoid space (SAS) and its breakdown products are neurotoxic and are the principal inducers of brain injury after subarachnoid hemorrhage (SAH). Recently, meningeal lymphatic vessels (MLVs) have been proven to play an important role in clearing erythrocytes that arise from SAH, as well as other macromolecular solutes. However, evidence demonstrating the relationship between MLVs and brain injury after SAH is still limited. Therefore, we performed this study to observe the effects of meningeal lymphatic impairment on early brain injury (EBI) after experimental SAH. Methods The MLVs of C57BL/6 male adult mice were ablated by injecting Visudyne into the cisterna magna and transcranially photoconverting it with laser light. The MLVs were then examined by immunofluorescence staining for lyve-1. Next, both the MLV-ablated group and the control group (normal mice) underwent filament perforation to model SAH or sham operation. We assessed the cortical perfusion of all the mice before SAH induction, 5 min after SAH and 24 h after SAH. In addition, we evaluated neurological function deficits by Garcia scores and measured brain water content at 24 h post SAH. Then, neuroinflammation and neural apoptosis in the mouse brain were also examined. Results Visudyne and transcranial photoconversion treatment notably ablated mouse MLVs. Five minutes after SAH induction, cortical perfusion was significantly impaired, and after 24 h, this impairment was ameliorated considerably in the control group but ameliorated only slightly or worsened in the MLV-ablated group. Additionally, the MLVablated group presented worse neurological function deficits and more severe brain edema than the control group. More notably, neuroinflammation and neural apoptosis were also observed. Conclusion Ablation of MLVs by Visudyne treatment exacerbated EBI after experimental SAH in mice. The worsening of EBI may have arisen from limited drainage of blood and other breakdown products, which are thought to cause brain edema, neuroinflammation, neuronal apoptosis and other pathological processes.

Intracranial aneurysms (IAs) are common cerebrovascular diseases that carry a high mortality rate, and the mechanisms that contribute to IA formation and rupture have not been elucidated. ADAMTS-5 (ADAM Metallopeptidase with Thrombospondin Type 1 Motif 5) is a secreted proteinase involved in matrix degradation and ECM (extracellular matrix) remodeling processes, and we hypothesized that the dysregulation of ADAMTS-5 could play a role in the pathophysiology of IA. Immunofluorescence revealed that the ADAMTS-5 levels were decreased in human and murine IA samples. The administration of recombinant protein ADAMTS-5 significantly reduced the incidence of aneurysm rupture in the experimental model of IA. IA artery tissue was collected and utilized for histology, immunostaining, and specific gene expression analysis. Additionally, the IA arteries in ADAMTS-5-administered mice showed reduced elastic fiber destruction, proteoglycan accumulation, macrophage infiltration, inflammatory response, and apoptosis. To further verify the role of ADAMTS-5 in cerebral vessels, a specific ADAMTS-5 inhibitor was used on another model animal, zebrafish, and intracranial hemorrhage was observed in zebrafish embryos. In conclusion, our findings indicate that ADAMTS-5 is downregulated in human IA, and compensatory ADAMTS-5 administration inhibits IA development and rupture with potentially important implications for treating this cerebrovascular disease.