Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus.

Neuronal progenitors in the adult hippocampus continually proliferate and differentiate to the neuronal lineage, and ischemic insult promotes hippocampal neurogenesis. However, newborn neurons show a progressive reduction in numbers during the initial few weeks, therefore, enhanced survival of newborn neurons seems to be essential for therapeutic strategy. Bcl-2 is a crucial regulator of programmed cell death in CNS development and in apoptotic and necrotic cell death.

Chronic mild reduction of cerebral perfusion pressure induces ischemic tolerance in focal cerebral ischemia.

Background And Purpose: Neurons acquire tolerance to ischemic stress when preconditioning ischemia occurs a few days beforehand. We focused on collateral development after mild reduction of perfusion pressure to find an endogenous response of the vascular system that contributes to development of ischemic tolerance.

Methods: After attachment of a probe, the left common carotid artery (CCA) of C57BL/6 mice was occluded.

Critical analysis of hemodynamic insufficiency by head-up tilt in patients with carotid occlusive disease.

Background: The objective of this study was to evaluate the diagnostic value of the head-up-tilt (HUT) test for detecting cerebral hemodynamic insufficiency in patients with major cerebral artery occlusion disease because such patients may benefit from extracranial - intracranial bypass surgery.

Methods And Results: In 13 cases of transient ischemic attacks in patients with carotid or middle cerebral artery occlusive disease, the HUT test was used to determine whether or not the symptoms appear during induced hypotension before investigating cerebral hemodynamics with positron emission tomography. Three of the 13 patients showed focal symptoms such as hemiparesis and limb shaking during the HUT test.

Adenovirus-mediated gene transfer of heparin-binding epidermal growth factor-like growth factor enhances neurogenesis and angiogenesis after focal cerebral ischemia in rats.

Background And Purpose: Recent studies have demonstrated that neurotrophic factors promote neurogenesis after cerebral ischemia. However, it remains unknown whether administration of genes encoding those factors could promote neural regeneration in the striatum and functional recovery. Here, we examined the efficacy of intraventricular injection of a recombinant adenovirus-expressing heparin-binding epidermal growth factor-like growth factor (HB-EGF) on neurogenesis, angiogenesis, and functional outcome after focal cerebral ischemia.

Cerebral hemodynamics and metabolism in adult moyamoya disease: comparison of angiographic collateral circulation.

Purpose: The extent of the hemodynamic and metabolic impairments in adult patients with moyamoya disease is still controversial. The aim of the present study was to evaluate the hemodynamic and metabolic status in relation to the development of basal moyamoya vessels (BMVs).

Methods: The cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured using PET in ten patients with ischemic adult moyamoya disease (mean age, 36.

CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice.

Cyclic AMP response element binding protein (CREB) is a transcription factor expressed constitutively primarily in neurons and is activated by phosphorylation at Ser(133) residue. CREB mediates expression of several neuroprotective proteins, including B-cell CLL/lymphoma 2 (BCL-2) and brain-derived neurotrophic factor (BDNF). Although phosphorylation of CREB after ischemia has been investigated extensively, CRE-mediated gene transcription after ischemia is not as well studied.

Equivalence of plaque score and intima-media thickness of carotid ultrasonography for predicting severe coronary artery lesion.

Carotid atherosclerosis appears to be predictive of myocardial infarction. Because several sonographical indices are available for carotid ultrasound (US), we compared "blindly" the potential utilities of those indices for predicting coronary lesions in 270 patients. Carotid atherosclerosis was evaluated by the following four indices: plaque score (PlaS), intima-media thickness (IMT) of common carotid artery (CCA-IMT), IMT of bulb to internal carotid artery (Bulb-ICA-IMT), and combined IMT measurement from all segments.

Hypertension associated with reduced plasma thrombomodulin levels and a hypercoagulable state in rats.

The plasma thrombomodulin (TM) level, an indicator of systemic endothelial cell damage, was measured in spontaneously hypertensive rats (SHR), deoxycorticosteron acetate (DOCA)-induced hypertensive rats and normotensive Wistar-Kyoto (WKY) rats to clarify its changes in hypertension. Plasma TM levels, measured by enzyme-linked immuno-sorbent assay, decreased with aging (5-20-weeks-old) in both SHR and WKY, and they were lower in SHR than age-matched WKY in all ages examined. Deoxycorticosteron acetate-induced hypertensive WKY also showed decreased TM levels compared with normotensive WKY.

Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation.

Caspase-3 is a major cell death effector protease in the adult and neonatal nervous system. We found a greater number and higher density of cells in the cortex of caspase-3(-/-) adult mice, consistent with a defect in developmental cell death. Caspase-3(-/-) mice were also more resistant to ischemic stress both in vivo and in vitro.

Expression of 150-kd oxygen-regulated protein in the hippocampus suppresses delayed neuronal cell death.

ORP150-150-kd oxygen-regulated protein-is a novel stress protein localized in the endoplasmic reticulum (ER). To investigate the role of ORP150 in delayed neuronal cell death, the authors examined its expression in the gerbil brain after an ischemic insult. The expression of ORP150 antigen, as well as its transcripts, was observed in the CA1 region after the occlusion of the common carotid artery, and the preconditioning enhanced this expression.

Protective effect of apolipoprotein E against ischemic neuronal injury is mediated through antioxidant action.

Recent studies have demonstrated that apolipoprotein E (APOE) deficiency worsened neuronal injuries after transient focal and global cerebral ischemia. However, the molecular mechanism underlying the protective effect of APOE remains uncertain, even though several mechanisms, including excitotoxicty, free radicals, and apoptosis, have been cited as causes of selective neuronal vulnerability in cerebral ischemia. In the present study, we first compared the vulnerability of cultured neurons prepared from APOE-knockout mice upon exposure to glutamate, hydrogen peroxide, and staurosporine.

Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats.

Recent studies demonstrated that neurogenesis in the adult hippocampus increased after transient global ischemia; however, the molecular mechanism underlying increased neurogenesis after ischemia remains unclear. The finding that proliferation of progenitor cells occurred at least a week after ischemic insult suggests that the stimulus was not an ischemic insult to progenitor cells. To clarify whether focal ischemia increases the rate of neurogenesis in the remote area, the authors examined the contralateral hemisphere in rats subjected to permanent occlusion of the middle cerebral artery.