Astrocytes react to oligemia in the forebrain induced by chronic bilateral common carotid artery occlusion in rats.
The effects of oligemia (moderate ischemia) on the brain need to be explored because of the potential role of subtle microvascular changes in vascular cognitive impairment and dementia. Chronic bilateral common carotid artery occlusion (BCCAO) in adult rats has been used to study effects of oligemia (hypoperfusion) using neuropathological and neurochemical analysis as well as behavioral tests. In this study, BCCAO was induced for 1 week, or 2, 4, and 6 months. Sensitive immunohistochemistry with marker proteins was used to study reactions of astrocytes (GFAP, nestin), and lectin binding to study microglial cells during BCCAO. Overt neuronal loss was visualized with NeuN antibodies. Astrocytes reacted to changes in the optic tract at all time points, and strong glial reactions also occurred in the target areas of retinal fibers, indicating damage to the retina and optic nerve. Astrocytes indicated a change in the corpus callosum from early to late time points. Diffuse increases in GFAP labeling occurred in parts of the neocortex after 1 week of BCCAO, in the absence of focal changes of neuronal marker proteins. No significant differences emerged in the cortex at longer time points. Nestin labeling was elevated in the optic tract. Reactions of microglia cells were seen in the cortex after 1 week. Measurements of the basilar artery indicated a considerable hypertrophy, indicative of macrovascular compensation in the chronic occlusion model. These results indicate that chronic BCCAO and, by inference, oligemia have a transient effect on the neocortex and a long-lasting effect on white matter structures.
Schmidt-Kastner
Rainald
R
Department of Neurology, Cerebral Vascular Disease Research Center, D4-5, University of Miami School of Medicine, PO Box 016960, Miami, FL 33101, USA. Rainald@ix.netcom.com
Aguirre-Chen
Cristina
C
Saul
Isabel
I
Yick
Linda
L
Hamasaki
Duco
D
Busto
Raul
R
Ginsberg
Myron D
MD
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D017536:Carotid Artery, Common / Q000473:pathology; D002452:Cell Count / Q000379:methods; D002908:Chronic Disease; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D010751:Phosphopyruvate Hydratase