Neural stem cells transplantation in cortex in a mouse model of Alzheimer's disease

Objective. The goal of this study was to elucidate the effect of neurospheres (NS) on dementia in the mouse model of nucleus basalis of Meynert (NBM) lesion. Methods. Mouse embryonic stem cell (ES) derived neurospheres were transplanted into the frontal association cortex and barrel field of S1 cortex of C57BL/6mice 4weeks after including a lesion of NBM by ibotenic acid, while other healthy mice that received ES cells served as control. Behavioral tests by 8-armradial maze were conducted 8 weeks after transplantation, and double staining of choline acetyltransferase (ChAT), serotonin, amyloid-βprotein (AP) and green fluorescent protein(GFP)12 weeks after transplantation.We found that the neurospheres transplanted into the mouse cortex survived and produced many ChAT-positive neurons and a few serotoninpositive neurons in and around the grafts. The working memory error decreased significantly in the mice grafted with neurospheres. In contrast, the ES cells developed into teratomas in all of the control mice and expressed no neurons, and the working memory deteriorated remarkably. Conclusions. Transplantation of neurospheres, but not ES cells, into the prefrontal and parietal cortices, dramatically alleviated the cholinergic deficits and recent memory disruption in the NBM lesioned mice

Differences in the neuronal stem cells survival, neuronal differentiation and neurological improvement after transplantation of neural stem cells between mild and severe experimental traumatic brain injury

We developed a novel protocol for generation and selective amplification of neural progenitor cells regionally specified to the rostral brain but not the spinal cord from mouse embryonic stem cells (ESCs). The neural progenitors could differentiate in vitro and in vivo into many cholinergic and a few GABAergic neurons but rarely into astrocytes. The transplanted neurospheres could survive in the hippocampus (CA3) of animals with mild traumatic brain injury (TBI). Twelve weeks after transplantation (a week after the behavioral test), we found significant cholinergic differentiation recognized as ChAT immunoreactivity in the eGFP+ transplanted cells. Moreover, the grafts contained a few GAD67+cells. However, we barely found GFAP+ astrocytes within the grafts. Furthermore, presynaptic formations of graft-derived neurons were recognized by immunohistochemistry of near the grafts aroundCA3. However, these findings were not observed in severe TBI group. So, we examined NGF, BDNF, and FGF-2 mRNA by RT-PCR in 12 mice including normal, mild TBI and severe TBI group. Increases in the neurotrophic factors’ mRNA were evident in the hippocampus on the ipsilateral side in the mild TBI group. Statistical analysis revealed significant differences between the mild and severe TBI groups. The data also revealed significant differences between the mild TBI and normal groups. The transplanted neurospheres could survive in the mild TBI animals, but not in the severe TBI group

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study

Aims To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol = 2.59 to = 100 to = 2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy

Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Values Predict the Development of Hepatocellular Carcinoma among Patients with Chronic Hepatitis C after Sustained Virological Response

Measurement of Wisteria floribundaagglutinin-positive human Mac-2 binding protein (WFA+-M2BP) in serum was recently shown to be a noninvasive method to assess liver fibrosis. The aim of this study was to evaluate the utility of serum WFA+-M2BP values to predict the development of hepatocellular carcinoma (HCC) in patients who achieved a sustained virological response (SVR) by interferon treatment. For this purpose, we retrospectively analyzed 238 patients with SVR who were treated with interferon in our department. Serum WFA+-M2BP values were measured at pre-treatment (pre-Tx), post-treatment (24 weeks after completion of interferon; post-Tx), the time of HCC diagnosis, and the last clinical visit. Of 238 patients with SVR, HCC developed in 16 (6.8%) patients. The average follow-up period was 9.1 years. The cumulative incidence of HCC was 3.4% at 5 years and 7.5% at 10 years. The median pre-Tx and post-Tx WFA+-M2BP values were 1.69 (range: 0.28 to 12.04 cutoff index (COI)) and 0.80 (range: 0.17 to 5.29 COI), respectively. The WFA+-M2BP values decreased significantly after SVR (P 60 years), sex (male), pre-Tx platelet count ( 2.0 COI) were associated with the development of HCC after SVR. Conclusion: Post-Tx WFA+-M2BP (> 2.0 COI) is associated with the risk for development of HCC among patients with SVR. The WFA+-M2BP values could be a new predictor for HCC after SVR

ヒカリ カンショウ ダンソウ ガゾウ シンダンホウ ニ ヨリ ヒョウカ シタ ケイドウミャク プラーク ハレツ ノ ケイタイガク テキ トクチョウ

博士(医学)熊本大

Endovascular Treatment of Acute Ischemic Stroke: Honolulu Shock and Thereafter

Recently, use of mechanical clot retrievers for acute stroke has gradually spread. However, 3 recent randomized controlled trials failed to show superiority of endovascular treatment compared to intravenous recombinant tissue plasminogen activator (IV rt-PA) alone or standard care. On the other hand, a Japanese nationwide survey demonstrated the efficacy of endovascular treatment in the IV rt-PA failed and ineligible patients, especially with the proximal artery occlusion such as the internal carotid artery. Earlier initiation and higher reperfusion of endovascular treatment seemed to be the main reason for the better result in this survey compared with the reported randomized studies. Because next-generation devices such as stent retrievers have been shown to provide better effects in terms of clinical outcomes compared with the Merci retriever, the efficacy of endovascular treatment is expected to be confirmed again by randomized controlled trials in the near future