Cell transplantation offers a novel therapeutic strategy for stroke; however, how transplanted cells function in vivo is poorly understood. In this study, we test the hypothesis that grafted human neural stem/progenitor cells enhance the endogenous repair that occurs after stroke. Moreover, we summarize the results from present pre-clinical and clinical studies and focus on the potential mechanisms (angiogenesis, BBB integrity, axonal sprouting, dendritic branching, and inflammation) in functional recovery after cell transplantation. We found that transplanted cells affected multiple parameters in the brain with different kinetics: early improvement in blood-brain barrier (BBB) integrity and suppression of inflammation was followed by a delayed spatio-temporal regulated increase in neovascularization. These events coincided with a bi-modal pattern of functional recovery: an early recovery independent of neovascularization, and a delayed hVEGF-dependent recovery coincident with neovascularization. Therefore, cell transplantation therapy offers an exciting multi-modal strategy for brain repair in stroke and potentially other disorders with a vascular or inflammatory component. We also demonstrated that transplanted cells enhance axonal sprouting and dendritic branching of host neurons after stroke, and that these plasticity changes correlated with cell-induced recovery. The Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) meeting was organized to bring together clinical and basic researchers with industry and regulatory representatives to assess the critical issues in the field and to create a framework to guide future investigations.
Cerebral aneurysm (CA) is a main cause of a lethal subarachnoid hemorrhage. Given the high incidence of CA in general population, the mechanisms of CA formation should be unlabelled and novel medical therapy for CA before rupture should be developed. The typical pathological feature of CA walls is the decrease of extracellular matrix (ECM). Decreased ECM results in the weakness of CA walls leading the enlargement and rupture of CA. In this article, we have reviewed the recent findings about the mechanisms of decreased ECM in CA walls mainly revealed by experiments using rodent CA models. ECM is the dynamic structure with the continuous synthesis and degeneration of matrix protein. In CA walls, the induced expressions of proteinases by chronic inflammation in arterial bifurcation are present and actively participated in the pathogenesis of CA. Further the synthesis of collagen is suppressed in CA wall through inflammatory stimulus in arterial walls. These results combined together indicate that both decreased synthesis and increased degeneration of ECM by chronic inflammation in CA walls contributes to CA formation. Further these results demonstrate the therapeutic potential of anti-inflammatory drugs for CA.
脳梗塞は死亡，身体障害の主な原因疾患であり，社会に及ぼす影響は大きい．後遺症を減らすためには，できるだけ早く診断し，血栓溶解療法などの適切な治療を行うことが重要である．脳梗塞の診断や進行・再発，薬剤反応性の予測が血液検査により可能となれば，早期から最適な治療選択が可能となり有用と考えられる．血漿タンパク質はダイナミックレンジが広く微量タンパク質の測定は困難であったが，質量分析器の発達によりプロテオミクス技術は格段に進歩し，血漿タンパク質の網羅的なハイスループット解析が可能となっている．われわれは脳梗塞患者における血漿タンパク質の変化を経時的，網羅的に探索し，種々のタンパク質が急性期から慢性期まで変動していることを明らかにした(Research for Biomarkers in Ischemic Stroke, REBIOS)．バイオインフォマティクスの手法を用いることで診断，予測マーカーを発見し，創薬ターゲットとなるタンパク質を発掘することが可能になると期待される．
Objectives: It has been reported that near-infrared (NIR) laser irradiation is effective in cerebral ischemia. We examined the effect of 808 nm laser diode irradiation on CBF in mice. The potential of NIR laser irradiation in the treatment of cerebral ischemia was also investigated. Methods: Male C57BL/6J mice were used. An 808 nm CW diode laser was applied to the hemisphere transcranially. CBF was measured with a non-contact laser Doppler blood perfusion imager. We measured directly nitric oxide in the brain tissue during NIR laser irradiation. To confirm the effect of pretreatment by NIR laser irradiation, we conducted the 1.6 W/cm2 NIR laser irradiation to the hemisphere transcranially for 30 minutes before bilateral common carotid artery occlusion (BCCAO). The control mice were also subjected to BCCAO without pretreatment by NIR laser irradiation. Results: Transcranial NIR laser irradiation increased local CBF by 30% compared to control value in mice. NIR laser irradiation also provoked a significant increase in cerebral NO concentration. Pretreatment by NIR laser irradiation improved residual CBF following bilateral carotid occlusion in mice. Conclusions: Our data suggest that targeted increase of CBF is available by NIR laser irradiation and it is concerned in NOS activity and NO concentration. Besides, NIR laser irradiation may have a protective effect for transient ischemia.
The aim of this study to evaluate treatment results for brain hemorrhage at Kyorin University Faculty of Medicine. We treated consecutive 152 cases of brain hemorrhage. We studied to examine their treatment contents and mRS (modified Rankin scale) at the time of their discharge. The surgeries were performed for 53 cases. Outcome of cerebellar and subcortical hemorrhage was relatively satisfactory compared to other bleeding sites and mRS: 0–2 was recognized in about 40% of the cases. In contrast, outcome of brain-stem hemorrhage was poor, and it caused 30% of overall mortality. There has been no specific evidence regarding surgical intervention for brain hemorrhage. As for putaminal hemorrhage which is likely to develop pyramidal tract disorder, the functional prognosis tends to deteriorate easily compared to cerebellar and subcortical hemorrhage, and it was considered to be the limit for judging prognostic evaluation based on functional assessment. Decisions for surgical indication for severe cases and significance of lifesaving effects include important life ethical issues, which are to be worked on in order to establish decision making methods which can be effective with limited time and manpower and to combine them with the development and application of regenerative medicine in future.
Insufficiencies of blood supply will more or less lead to brain dysfunction. Cognitive impairment caused by such cerebrovascular insufficiency was called vascular cognitive impairment (VCI), a clinical syndrome composed of a markedly heterogeneous group of diseases rather than a unique pathological process. It includes large vessel disease with strategic single or multiple strokes and small vessel disease with progressive damage to the basal ganglia and/or the white matter. VCI was previously believed to be distinct from Alzheimer’s disease (AD) resulting from a neurodegenerative process. However, such simple dichotomy needs to be reconsidered in light of the shared features between AD and VCI: these two disorders increase in prevalence with age, frequently occur concomitantly, and considerably overlaps in their symptomatology, pathophysiology, and comorbidity. So-called ‘mixed’ brain pathologies, mainly comprising of AD pathology and cerebral infarctions, are reported to account for most dementia cases in community-dwelling elderly people. Consistent with this notion, the contributors to attributable risks at death for dementia include small vessel disease and multiple vascular pathologies, which are no less than those of the main pathological hallmarks of AD, neocortical neuritic plaques and neurofibrillary tangles. Importantly, the multifactorial aspects of cognitive impairment have been incorporated in the dynamic polygon hypothesis, which takes into account the contributions of strokes of all sizes and white matter hyperintensities in parallel to those of plaques and tangles. In terms of the treatment of dementia, it is undoubtedly important to control vascular risk factors for the prevention of VCI. However, even in patients who have AD without cerebrovascular disease, treatment of vascular risk factors is associated with a slower decline in the Mini-Mental State Examination score. Therefore, physicians should always bear in mind that vascular risk factors need to be controlled to achieve a reduction in the risk of dementia, even if the dementia is caused by AD.
われわれは脳卒中にかかわる医療と福祉従事者(stroke care worker)にstroke teamを中心として教育活動を行ってきた．2002年より北海道中空知圏域の非脳卒中専門医療機関への教育を開始し，市民公開講座，PCEC/PSLS，ISLSを推進し，医学生および臨床研修医に加え，2010年には介護福祉従事者へ教育対象を広げた．この間，国家試験問題の解析から，多職種が受けた脳卒中教育の程度はさまざまであることを明らかにし，一般市民向けとは異なるstroke care worker向けの「脳卒中テキスト(仮称)」の作成を提案した．脳卒中学・医療の向上には人材教育が重要である．教育は，量から質を伴ったものへ，卒前から卒後まで，院内から院外へ対象を広げることが望ましく，標準教材の開発や「教育に協力することの意義」について市民へ啓発することも合わせて必要である．
TIA is a medical emergency. Because, the risk of stroke early after TIA is very high. It has been reported that immediate evaluation and management of TIA substantially reduced the risk of subsequent stroke. Therefore, TIA patients should be evaluated and treated as soon as possible in a TIA clinic during 24 hours for 365 days. Based on these backgrounds, we conducted an international multicenter cooperative, investigator-driven, web-based observational study (TIAregistry.org). Five thousand patients with TIA or minor stroke (Rankin 0 or 1) within 7 days after the onset will be recruited and followed up for 5 years. The primary endpoint is non-fatal stroke, non-fatal MI or vascular death. The secondary endpoint is any vascular event or endovascular intervention. The investigational endpoints include quality of treatments, clinical manifestations, etiologies, times from first medical attention, and risk prediction scores. The background demographics include neurological symptoms, brain MRI and MRA, carotid ultrasonography, echo cardiography, blood pressure, CBC, lipids, and glucose. More than 5,000 patients will be recruited until July, 2011. Six Japanese stroke centers join the registry to recruit the target number of 300 patients. This registry may provide important information on evaluation and management of TIA as a medical emergency.