Department of Pharmacology 1, Nagasaki University GraduateSchool of Biomedical Sciences, Nagasaki 852-8523, Japan.
Cell Mol Neurobiol. 2010 Mar;30(2):283-7. doi: 10.1007/s10571-009-9450-y.
The stroke-prone spontaneously hypertensive rat (SHRSP) is vulnerable to delayed neuronal death (DND) in the CA1 subfield of the hippocampus after the transient forebrain ischemia by the occlusion of the bilateral carotid arteries. The present study was designed to show that the genetic factors independent of high blood pressure contributed to the high incidence of DND in SHRSP. Male rats of the four strains, SHRSP/Izm, SHRSP/Ngsk, SHR/Izm and a congenic strain for the blood pressure quantitative trait locus on chromosome 1 [SHRSP.WKY-(D1Wox29-D1Arb21)/Izm]were used in the experiments. At 13 weeks of age, the bilateral carotid arteries of rats were occluded for 10 min under anesthesia with their body temperature kept at 37 degreeC. Seven days after the transient ischemia, the loss of the pyramidal cells in the CA1 was evaluated histologically. In some experiments, the blood flow was monitored with a laser Doppler flowmeter during the transient ischemia. The blood pressure in SHRSP/Izm was significantly greater than that in the other three strains. The incidence of DND, however, was not significantly different among SHRSP/Izm, SHRSP/Ngsk and the congenic strain (82, 74 and 65%, respectively), while SHR/Izm showed a significantly lower incidence (20 percent). Neither a significant correlation between the incidence of DND and the blood flow reduction during the occlusion, nor a significant inter-strain difference in the blood flow reduction was observed. The genetic factors independent of high blood pressure may contribute to the greater susceptibility to DND in SHRSP.
易发生中风的自发性高血压大鼠（SHRSP）在双侧颈总动脉阻塞引起的短暂前脑缺血后，海马 CA1 亚区易发生迟发性神经元死亡（DND）。本研究旨在表明，与高血压无关的遗传因素可能导致 SHRSP 中 DND 的高发生率。在实验中使用了四个品系的雄性大鼠，即 SHRSP/Izm、SHRSP/Ngsk、SHR/Izm 和一个位于 1 号染色体上的血压数量性状基因座的同系品系[SHRSP.WKY-（D1Wox29-D1Arb21）/Izm]。在 13 周龄时，大鼠在 37°C 的体温下用全身麻醉将双侧颈总动脉阻塞 10 分钟。短暂缺血后 7 天，通过组织学评估 CA1 锥体神经元的丢失。在一些实验中，使用激光多普勒流量计在短暂缺血期间监测血流。SHRSP/Izm 的血压明显高于其他三个品系。然而，DND 的发生率在 SHRSP/Izm、SHRSP/Ngsk 和同系品系之间没有显著差异（分别为 82%、74%和 65%），而 SHR/Izm 的发生率明显较低（20%）。DND 的发生率与阻断期间的血流减少之间没有显著相关性，也没有观察到不同品系之间的血流减少存在显著差异。与高血压无关的遗传因素可能导致 SHRSP 对 DND 的易感性增加。
