Effects of the transcription factor Olig1 on the differentiation and remyelination of oligodendrocyte precursor cells after focal cerebral ischemia in rats.

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is important for remyelination in the central nervous system. Nevertheless, this process is often limited and incomplete in ischemic injury. Oligodendrocyte transcription factor 1 (Olig1) is important for the maturation of OPCs and the repair of demyelinated lesions. However, how Olig1 modulates the development of OPCs or the remyelination associated with ischemic injury remains unclear. The present study aimed to examine alterations in OPCs, and the expression of myelin and Olig1, at different time-points after focal cerebral ischemia using immunohistochemistry and western blot techniques to elucidate the role of Olig1 in the maturation of OPCs and remyelination. The present results showed that the expression of Olig1 significantly decreased at 1 day after middle cerebral artery occlusion (MCAO) and returned to normal levels from day 3 to 28. Additionally, Olig1 was found to translocate into the nucleus following ischemia in the brain. The number of OPCs in the ischemic striatum significantly declined at days 1 and 3 following MCAO, and increased at days 7, 14 and 28 compared with the control. The expression of myelin basic protein, a marker of mature oligodendrocytes and myelin, gradually decreased from day 1 to 7 after ischemia and recovered at day 14 and 28; however, the levels were lower than those in the control group. The present results indicated that the restored normal level of Olig1 following ischemia may play an important role in the maturation of OPCs through its translocation into the nucleus, where it may promote the growth and development of myelin under pathological conditions. However, this endogenous recovery mechanism fails to fully repair the demyelinated lesion. The data of the present study may help clinicians understand the expression pattern of Olig1 and its potential role in endogenous remyelination after ischemia, which may have implications for the treatment of diseases that lead to demyelination.

Middle cerebral artery stenosis increased the risk of vascular disease mortality among type 2 diabetic patients.

BACKGROUND: In Chinese populations, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion, and has been shown to be associated with an increased risk of secondary stroke mortality, but has yet to be reported for primary events. We assess whether asymptomatic MCA stenosis is associated with mortality in Chinese type 2 diabetic patients. METHODS: The presence of MCA stenosis was determined by transcranial Doppler and mortality data were collated in the Hong Kong Death Registry. Cox proportional hazards regression was used to determine if the MCA stenosis (n = 272, 53.7% 2-vessel disease) in 2,197 diabetics was associated with all-cause or vascular disease mortality, including after adjustment for conventional vascular risk factors. Anthropometric and fasting biochemical parameters were compared between diabetic patients with MCA stenosis and without evidence of stenosis. RESULTS: A total of 191 deaths were identified (30.9% of vascular disease origin) during a follow-up of 18,279 patient years over 8.32 years. After adjustment for age, gender and diabetes duration, the hazard ratios for vascular mortality for 1- and 2-vessel disease were 2.47 (95% CI = 1.13-5.38) and 4.47 (95% CI = 2.24-8.82), p < 0.001 for trend, for increasing vascular mortality with increasing severity of cerebrovascular involvement, but 0.81 (95% CI = 0.45-1.47) and 2.23 (95% CI = 1.45-1.47), p = 0.001 for trend, for all-cause mortality. For vascular mortality, further adjustments for anthropometric and fasting biochemical parameters, or existing disease and treatment history increased the hazard ratios for 1-vessel disease slightly but attenuated the risk for 2-vessel disease evidently, 2.81 (95% CI = 1.10-7.16) and 2.85 (95% = CI 1.11-7.33), p = 0.026. CONCLUSION: The presence of MCA stenoses was an independent predictor of vascular mortality in these diabetics. More aggressive treatment of risk factors in these subjects merits further evaluation.

dl-3n-butylphthalide prevents stroke via improvement of cerebral microvessels in RHRSP.

The purpose of the study is to establish a model of cold-induced stroke in hypertensive rats, and to study the preventive effect of dl-3n-butylphthalide ( NBP ) on stroke. Stroke-prone renovascular hypertension(RHRSP) was created in Sprague-Dawley rats. The animals were assigned randomly to NBP, aspirin treated and vehicle control group, with administration of the medications for 7 days, and then subjected to cold treatment in an environmentally controlled chamber for 3 days to induce the occurrence of stroke. The incidence of stroke, the volume of the brain lesion, patency of the microvessels by FITC-dextran perfusion and the number of microvessels by immunohisochemical detection of vwF were investigated. Cold induced different types of stroke in RHRSP. The incidence of ischemic stroke and the volume of the infarct were decreased, and the perfused microvessels were increased with NBP pretreatment. Our data suggest that NBP prevents cold-induced ischemic stroke via improvement of cerebral microvessels.

Increasing severity of cardiovascular risk factors with increasing middle cerebral artery stenotic involvement in type 2 diabetic Chinese patients with asymptomatic cerebrovascular disease.

OBJECTIVE: To identify determinants associated with increasing severity of middle cerebral artery (MCA) stenosis in asymptomatic Chinese type 2 diabetic patients with and without MCA stenosis determined using transcranial Doppler. Conventional risk factors contribute to the pathogenesis of ischemic stroke, and differences in the pattern of these may explain the heterogeneity of disease presentation in different populations. In Chinese patients, MCA stenosis is the most commonly identified intracranial vascular lesion. RESEARCH DESIGN AND METHODS: Anthropometric and fasting biochemical parameters were compared between type 2 diabetic patients with MCA stenosis in one (n = 185) or both (n = 200) vessels and 1,492 type 2 diabetic patients without evidence of stenosis. RESULTS: Increasing MCA stenotic vascular involvement was associated with significantly increasing age, duration of diabetes, systolic blood pressure, and LDL cholesterol, but with lower glucose levels. There was also an increased prevalence of hypertension, dyslipidemia, and use of blood pressure-and glucose-lowering agents in the patients with MCA stenosis. Concomitant significant increases in the prevalence of peripheral vascular disease and retinopathy were also observed in the patients with MCA stenosis. CONCLUSIONS: Transcranial Doppler examination identified stenosis in one or both MCAs in over one-fifth of the Chinese type 2 diabetic subjects without symptoms of cerebrovascular disease. A number of conventional cardiovascular risk factors were closely associated with MCA stenosis. This technique may allow the identification of a particularly high-risk group, and further studies are required to determine whether asymptomatic MCA stenosis is predictive of primary cerebrovascular events and whether intensive treatment of risk factors would reduce the risk.

Trigeminal nerve and facial nerve palsy after combined spinal-epidural anesthesia for cesarean section.

A case of emergency cesarean section due to a prolonged second stage of labor in a 29 year-old woman is presented. She had trigeminal nerve and facial nerve palsy after combined spinal-epidural anesthesia for cesarean section.

Modulatory role of estradiol in nicotinic antinociception in adult female rats.

AIMS: Differences in the response to nicotinic analgesia in males and females have been suggested by recent studies, and such differences are presumed to be due to the regulatory effects of gonadal hormones. The aim of this study was to investigate nicotinic antinociception and the effect of estradiol (E2) on this response in female rats. MAIN METHODS: Ovariectomized female rats were implanted with subcutaneous silastic tubes containing E2. On day 28 after implantation, epibatidine, a high-potency nicotinic acetylcholine receptor (nAChR) agonist, was administered intrathecally, and antinociception at the spinal level was assessed by the tail-flick test. In addition, immunohistochemical staining for nAChRalpha4 was performed in spinal cord sections. KEY FINDINGS: We found that female rats showed shorter nociceptive latencies than males, but there was no effect of ovarian status. However, OVX significantly increased epibatidine-induced antinociception compared to that in intact females, and this increase was attenuated by E2 treatment. In addition, OVX resulted in increased nAChRalpha4 immunostaining in the dorsal horn compared to that in intact females, and this increase was also attenuated by E2 treatment. SIGNIFICANCE: Results of this study provide new evidence that E2 modulates epibatidine-induced antinociception at the spinal level in female rats.

Enhanced angiogenesis with dl-3n-butylphthalide treatment after focal cerebral ischemia in RHRSP.

Appropriate restoration of blood flow via angiogenesis is critical for the recovery from ischemic stroke. Previously, we reported that treatment with dl-3n-butylphthalide (NBP) increases the number of local potent cerebral microvessels. However, the underlying mechanism remained unclear. The present study was conducted to test whether NBP enhances post-ischemic cerebral angiogenesis via vascular endothelial growth factor (VEGF) and hypoxia induced factor-1 alpha (HIF-1 alpha). Stroke-prone renovascular hypertensive rats (RHRSP) were used to create middle cerebral artery occlusion (MCAO) model. NBP was given 80 mg/kg per d for 10 consecutive days, starting 12, 24, 48 and 72 h respectively after MCAO. Neurological function was assessed daily and infarct volume as well as the expressions of CD31, VEGF, HIF-1 alpha and bFGF was detected 13 days after MCAO. The administration of NBP starting within 24 h after MCAO enhanced recovery of neurobehavioral function, reduced infarct volume, increased the quantity of CD31 positive vessels, and up-regulated expressions of VEGF and HIF-1 alpha. These findings suggest that treatment with NBP within 24 h post-ischemic stroke rescues brain tissue by enhancing angiogenesis associated with up-regulation of VEGF and HIF-1 alpha expressions.

[Changes in endothelial cellular adhesion molecule mRNA expressions in the cerebral blood vessels of rats with prestroke condition caused by simulated cold wave].

OBJECTIVE: To study the changes in the mRNA expression of endothelial cellular adhesion molecules in the cerebral blood vessels in rats with prestroke condition caused by simulated cold wave. METHODS: Two-kidney two-clip renovascular hypertension was induced in 48 male SD rats, which were subsequently randomly assigned into cold wave exposure and non-exposed group (n=24). Each group was further divided into 4 sub-groups according to their systolic blood pressure, namely the sham-operated group with blood pressure (BP)<140 mmHg, mild hypertensive group with BP of 160-199 mmHg, moderate hypertensive group with BP of 200-219 mmHg, and severe hypertensive group with BP no less than 220 mmHg. Cold wave exposure was simulated by housing the rats in an artificial climate chamber with 3 cycles of 12 h light at 22 degrees celsius; and 12 h dark at 4 degrees celsius;. The non-exposed group was kept at 22 degrees celsius; throughout the experiment. After the exposure, the rats were sacrificed and the tissues of the frontal lobe were slice into 2.0-mm-thick coronal sections for real-time RT-PCR detection of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and p-selectin mRNA expressions. The 5.0-microm-thick frozen sections from the bregma section underwent in situ hybridization of VCAM-1, ICAM-1, and p-selectin. The other sections were stained with HE to observe the infarct lesions, and the rats with cerebral infraction were excluded from the statistical analysis. RESULTS: In rats with cold wave exposure-induced prestroke condition and BP <220 mmHg, VCAM-1, ICAM-1, and p-selectin mRNA expressions all increased compared with those in the non-exposed group. In rats with BP>or=220 mmHg and cold exposure, the expressions all decreased to some extent compared with those in the non-exposed treatment. In the non-exposed rats, a positive correlation of BP to VCAM-1, ICAM-1, and p-selectin mRNA expressions were noted, and this correlation was also found in cold-wave-exposed rats with BP <220 mmHg; VCAM-1, ICAM-1, and p-selectin mRNA expressions decreased dramatically in the exposed rats with BP >or=220 mmHg compared with those in rats with BP <220 mmHg. CONCLUSION: Persistent and severe hypertension impairs the modulatory function of the cerebral vascular endothelia, which is a prerequisite for the stroke vulnerability. The modulatory function deteriorates as the BP further increases.

Middle cerebral artery stenosis in type II diabetic Chinese patients is associated with conventional risk factors but not with polymorphisms of the renin-angiotensin system genes.

BACKGROUND: Conventional and genetic risk factors have been reported to play a role in the pathogenesis of ischaemic stroke, and differences may explain the heterogeneity of disease presentation in different populations. In Chinese, middle cerebral artery (MCA) stenosis is the most commonly identified intracranial vascular lesion. The involvement of renin-angiotensin system (RAS) gene polymorphisms in this condition has not been determined. OBJECTIVES: To determine whether conventional and RAS genetic vascular risk factors are associated with MCA stenosis, asymptomatic Chinese type II diabetic patients with and without MCA stenosis matched for age, gender and diabetes duration were compared. METHODS: Biochemical parameters and the genotype and allele frequencies of three RAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT(1)R) A1166C polymorphisms were then compared between 217 diabetics with and 490 matched diabetic controls without MCA stenosis selected from 2,202 diabetics. RESULTS: MCA stenosis was associated with significantly increased systolic blood pressure, LDL-cholesterol and albuminuria, yet diastolic blood pressure and glucose levels were lower. There was an increased prevalence of hypertension and use of blood pressure-lowering agents in the MCA stenosis patients. Albuminuria was also more commonly found in these patients. Hypertensive status, systolic blood pressure and albuminuria were strong, independent predictors of the presence of MCA stenosis. No differences in the RAS polymorphism distributions were observed between patients with and without MCA stenosis. CONCLUSIONS: In these asymptomatic type II diabetics, blood pressure indices and albuminuria, but not RAS gene polymorphism, were closely associated with MCA stenosis.