Brain blood flow restoration 'rescues' chronically damaged rat CA1 neurons.
Middle aged rats (13 months) were subjected to chronic cerebrovascular insufficiency (CVI) for 9 weeks using a 3-vessel occlusion technique. This CVI injury targets CA1 neuron damage selectively. Three groups of rats had their cerebral blood flow restored after 1, 2 or 3 weeks following CVI by removal of their carotid artery occluders. Another rat group did not undergo deocclusion for the 9 week observation period. Rats were tested for memory acquisition and retention 6 and 9 weeks after CVI using a modified water maze test. At the end of the 9 weeks, cerebral blood flow was measured in the fronto-parietal cortex and rats were killed by fixation-perfusion. Hippocampal morphometry was done to assess the % of damaged CA1 neurons and the density of GFAP-positive hyperplasia and hypertrophy. Results show that restoration of cerebral blood flow 1 and 2 weeks after CVI but not after 3 weeks of CVI, reversed a significant increase in reactive astrocytosis and prevented memory impairment in these deoccluded rats when compared to the non-deoccluded group. It appears from these results that 'neuronal rescue' of CA1 neurons is possible when cerebral blood flow is restored in rats subjected to chronic CVI during a 2 week (but not 3 week) 'window of opportunity'. This chronic brain ischemia model may be useful in screening potential therapy in patients with dementia where spatial memory impairment and hippocampal damage may be manifested.
de la Torre
J C
JC
Division of Neurosurgery, University of Ottawa, Faculty of Medicine, Ont. Canada.
Fortin
T
T
Park
G A
GA
Pappas
B A
BA
Richard
M T
MT
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division; D002560:Cerebrovascular Circulation; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006984:Hypertrophy; D008297:Male; D008568:Memory / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D011712:Pyramidal Tracts / Q000098:blood supply / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013028:Space Perception
D005904:Glial Fibrillary Acidic Protein