Hypertension downregulates the expression of brain-derived neurotrophic factor in the ischemia-vulnerable hippocampal CA1 and cortical areas after carotid artery occlusion.
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.
Lee
Tsong-Hai
TH
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. thlee@adm.cgmh.org.tw
Yang
Jen-Tsung
JT
Kato
Hiroyuki
H
Wu
June Hsieh
JH
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D017536:Carotid Artery, Common / Q000502:physiology; D016893:Carotid Stenosis / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger