Lee Tsong-Hai, Yang Jen-Tsung, Kato Hiroyuki, Wu June Hsieh
Stroke Section, Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, College of Medicine, Chang Gung University, 5 Fu-Hsing St., Kuei-Shan, Tao-Yuan, 33333 Taiwan.
Brain Res. 2006 Oct 20;1116(1):31-8. doi: 10.1016/j.brainres.2006.07.117. Epub 2006 Sep 7.
We studied the effect of hypertension on brain damage and brain-derived neurotrophic factor (BDNF) expression in the hippocampal formation and cerebral cortex after permanent occlusion of bilateral common carotid arteries (CCA). Two groups of rats were used, including normotensive Wistar-Kyoto (WKY) rat and spontaneous hypertensive rat (SHR). Each group contained sham operation, 1 week and 4 weeks after bilateral CCA occlusion (n=5-10 in each time point). The blood pressure showed a significant elevation in WKY rats from 1 h after operation to 4 weeks before sacrifice (P<0.05), but was not changed in SHR (P>0.05). However, rectal temperature showed no significant change after operation in WKY rat and SHR (P>0.05) and showed no significant difference at any time point between WKY rat and SHR (P>0.05). Hematoxylin and eosin staining showed SHR had a significantly larger necrotic volume than WKY rats (n=10 in each group, 6044+/-6895 microm(3) vs. 144+/-174 microm(3), P<0.05) at 4 weeks after ischemia. In SHR, BDNF immunoreactivity and mRNA decreased significantly from 1 week to 4 weeks in both the hippocampal CA1 and cortical areas (P<0.01) but decreased transiently in dentate gyrus. However, in WKY rats, BDNF immunoreactivity and mRNA decreased transiently at 1 week (P<0.05) and recovered at 4 weeks after cerebral ischemia. Our study demonstrates that after bilateral CCA occlusion, preexisting hypertension may aggravate the brain injury and downregulate the expression of BDNF immunoreactivity and mRNA in the ischemia-vulnerable hippocampal CA1 and cortical areas but not in ischemia-resistant dentate gyrus.
我们研究了双侧颈总动脉(CCA)永久性闭塞后高血压对海马结构和大脑皮质中脑损伤及脑源性神经营养因子(BDNF)表达的影响。使用了两组大鼠,包括血压正常的Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)。每组均包含假手术组、双侧CCA闭塞后1周和4周组(每个时间点n = 5 - 10)。WKY大鼠术后1小时至处死前4周血压显著升高(P < 0.05),但SHR大鼠血压无变化(P > 0.05)。然而,WKY大鼠和SHR大鼠术后直肠温度无显著变化(P > 0.05),且在任何时间点WKY大鼠和SHR大鼠之间直肠温度均无显著差异(P > 0.05)。苏木精-伊红染色显示,缺血4周时,SHR大鼠的坏死体积显著大于WKY大鼠(每组n = 10,6044±6895立方微米 vs. 144±174立方微米,P < 0.05)。在SHR大鼠中,海马CA1区和皮质区的BDNF免疫反应性和mRNA从1周龄到4周龄均显著降低(P < 0.01),但在齿状回中短暂降低。然而,在WKY大鼠中,脑缺血后1周BDNF免疫反应性和mRNA短暂降低(P < 0.05),4周时恢复。我们的研究表明,双侧CCA闭塞后,先前存在的高血压可能会加重脑损伤,并下调缺血易损的海马CA1区和皮质区中BDNF免疫反应性和mRNA的表达,但不会下调缺血耐受的齿状回中的表达。