关键词: 2VO, two-vein occlusion Akt, protein kinase B BBB, blood-brain-barrier CAI, cerebral arterial ischemia CBF, cerebral blood flow CVI, cerebral venous ischemia Cerebral blood flow Cerebral cortex Cerebral ischemia HMG-CoA, 3-hydroxy 3-methylglutaryl coenzyme A HSP, heat shock protein IL-6, Interleukin-6 JNK, Jun-NH2-terminal kinase LDL, low-density lipoprotein LDU, Laser Doppler-unit MAPK, mitogen-activated protein kinase MCAO, middle cerebral artery occlusion Neuronal apoptosis PI3K, phosphatidylinositol 3-OH kinase Pravastatin sodium TNFα, Tumor Necrosis Factor‐α Vein

来  源:   DOI:10.1016/j.ibneur.2023.02.002   PDF(Pubmed)

Abstract:
UNASSIGNED: Pravastatin sodium is reported to have multiple beneficial effects in cerebral atherosclerosis and neuronal injury; however, the preventive effects on cerebral venous ischemia are still unknown. Herein, we aimed to examine the neuroprotective effects of transoral prior administration of pravastatin sodium against cerebral cortical venous ischemia with suppression of apoptosis.
UNASSIGNED: Thirty 8-week-old male Wistar rats were divided equally into two study groups (n = 15 vs. n = 15); the pravastatin group was fed 1% pravastatin sodium with their usual diet for 2 weeks, while the control group only received the usual diet. Two-vein occlusion (2VO) model was applied for this study, and two adjacent cortical veins in each animal were permanently occluded photochemically with rose bengal dye. During photo-thrombosis, regional changes of the cerebral blood flow (CBF) in area of the venous ischemia were recorded. At 48-h after 2VO, animals were euthanized using perfusion fixation, and we histologically measured ratios of infarcted area to contralateral hemisphere, and counted Bax- and Bcl-2-positive cells in the penumbra to investigate the implications for apoptosis.
UNASSIGNED: The ratio of infarcted area was significantly decreased in the pravastatin group compared to the control group (P < 0.01). The number of Bax-positive cells also decreased significantly in the pravastatin group (P < 0.01). In contrast, immunolabeling for Bcl-2 was essentially negative in all areas in both groups. There were also no significant differences in regional CBF changes after 2VO between the two groups (P = 0.13).
UNASSIGNED: Pre-emptive administration of pravastatin sodium mixed in the food has neuroprotective effects against cerebral cortical venous ischemia with suppression of apoptosis associated with inhibition of Bax expression but has little influence on regional CBF.
摘要:
未经证实:据报道,普伐他汀钠在脑动脉粥样硬化和神经元损伤中具有多种有益作用;然而,对脑静脉缺血的预防作用尚不清楚。在这里,我们旨在研究普伐他汀钠经口预先给药对大脑皮质静脉缺血并抑制细胞凋亡的神经保护作用。
UNASSIGNED:将30只8周龄雄性Wistar大鼠平均分为两个研究组(n=15vs.n=15);普伐他汀组以其常规饮食喂养1%普伐他汀钠2周,而对照组只接受常规饮食。本研究采用两静脉闭塞(2VO)模型,每只动物的两个相邻的皮质静脉被玫瑰孟加拉染料光化学永久封闭。在光血栓形成期间,记录静脉缺血区域的脑血流量(CBF)的区域变化。2VO后48小时,使用灌注固定对动物实施安乐死,我们从组织学上测量了梗死面积与对侧半球的比率,并计数半影中的Bax和Bcl-2阳性细胞以研究其对细胞凋亡的意义。
UNASSIGNED:普伐他汀组梗死面积比对照组明显降低(P<0.01)。普伐他汀组Bax阳性细胞数也显著减少(P<0.01)。相比之下,在两组的所有区域中,Bcl-2的免疫标记基本上为阴性。2VO后两组的区域CBF变化也没有显着差异(P=0.13)。
UNASSIGNED:预先给予食物中混合的普伐他汀钠对大脑皮质静脉缺血具有神经保护作用,抑制与抑制Bax表达相关的细胞凋亡,但对局部CBF影响很小。
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