Mild ischemia produces hippocampal neuronal death in stroke-prone spontaneously hypertensive rats.
The blood flow in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) and Wistar Kyoto (WKY) rats during occlusion of the carotid arteries was examined because it has been previously found that 2-vessel occlusion (2-VO) induces delayed neuronal death (DND) in the pyramidal cells of the CA1 hippocampal area in SHRSPs but not in WKY rats. DND was also examined in 4-week-old SHRSPs, which are as yet normotensive, in order to reveal the involvement of the development and maintenance of severe hypertension in DND in SHRSPs. Before, during and after occlusion, the blood flow in the hippocampus was continuously monitored by laser Doppler flowmetry, wherein the probe was connected to a plastic fiber that was implanted in the CA1 subfield of animals. The change in blood flow was determined by comparing its rate during occlusion to the preoperative value. DND was confirmed by histological examination at 7days after the operation. The rate of blood flow during 2-VO was similar between the SHRSPs (42.6% +/- 5.3%) and WKY rats (49.0% +/- 14.3%). WKY rats that underwent 4-vessel occlusion (4-VO), which induces DND in WKY rats, exhibited a severely decreased blood flow of 13.7% of the preoperative value. DND was also observed in 4-week-old SHRSPs that underwent 2-VO, and the incidence was identical to that in 12-week-old SHRSPs. The present results suggest that the DND that occurs in SHRSPs due to 2-VO is not a result of the more severe reduction in blood supply during the occlusion than that in WKY rats, and secondary damage due to severe hypertension but is caused by some genetic factors due to which the pyramidal neurons of SHRSPs are more vulnerable to ischemic insult than those of WKY rats are.
Kinugawa
Hidekazu
H
Department of Pharmacology1, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Sakurai-Yamashita
Yasuko
Y
Niwa
Masami
M
D000367:Age Factors; D000818:Animals; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D007511:Ischemia / Q000150:complications*; D008297:Male; D017966:Pyramidal Cells / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000209:etiology* / Q000473:pathology*