Transient global brain hypoxia-ischemia in adult rats: neuronal damage, glial proliferation, and alterations in inositol phospholipid hydrolysis.
A model of ischemic-hypoxic brain injury which combines bilateral occlusion of common carotid arteries for 10 min and mild hypoxia (15% O2 for 10 min before and during occlusion) was developed. Global ischemia was assessed by a simplified EEG recording indicating isoelectric line, i.e. full arrest of cortical electrical activity. Histological examination of brain 7 days after ischemic insult showed from moderate to severe damage, mainly in the cerebral cortex (layers III, V and VI) and hippocampus (mainly CA1 subfield). The injury consisted of neuronal degeneration and necrosis with nuclear pyknosis and karyorrhexis. Immunohistochemical staining for gliofibrillar acidic protein showed a marked glial proliferation in the cerebral cortex and hippocampus. In the cortical slices, inositol phosphates accumulation stimulated by excitatory amino acid agonists (ACPD, ibotenate and quisqualate), as well as by norepinephrine and carbachol, was enhanced significantly (p < 0.01) with respect to sham-operated rats 7 days, but not 24 h, after the ischemic insult. The overall data show that the relatively simple transient brain hypoxia/ischemia rat model produces full arrest of cortical EEG, histopathological alterations and those relative to post-receptor neurochemical mechanisms characteristic of four-vessel occlusion model.
Fortuna
S
S
Laboratory of Pharmacology, Istituto Superiore di Sanità, Roma, Italy.
Pestalozza
S
S
Lorenzini
P
P
Bisso
G M
GM
Morelli
L
L
Michalek
H
H
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D002455:Cell Division; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006868:Hydrolysis; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists
D005904:Glial Fibrillary Acidic Protein; D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate