Neuronal uptake of plasma proteins after transient cerebral ischemia/hypoxia. Immunohistochemical studies on experimental animals and human brains.
Rapid uptake of plasma proteins into damaged neurons has been demonstrated previously after lesions which cause early breakdown of the blood-brain barrier (BBB). The present study was undertaken to see whether a similar uptake occurred after hypoxic/ischemic episodes in men and experimental animals. Forebrain ischemia was produced in rats by a combination of carotid clamping and hypotension for 15 min, followed by recirculation for 6 h, 24 h, 48 h and 5 d. Paraffin sections from the brains were incubated with antiserum against albumin, and parallel sections were stained with hematoxylin and eosin (H & E). Breakdown of the BBB with extravasation of albumin was seen after 6 h in the lateral reticular nucleus of the thalamus, the dorsolateral striatum, and in restricted areas of the cerebral cortex. Uptake of albumin into damaged neurons was seen in the same structures, and partly before reliable changes were observed in routinely stained sections. With longer survival periods, the staining of the neuropil became stronger and more neurons in the damaged areas were positively labeled. After 48 h and 5 d many neurons in the hippocampal sector CA1 had also taken up plasma proteins. A similar uptake of plasma proteins into damaged neurons was seen in brains from patients with histological evidence of hypoxic injury. Even the small leakage of proteins that occurs after hypoxic/ischemic lesions is thus sufficient to give a definite immunostaining of damaged neurons.
Løberg
E M
EM
Department of Pathology, Ullevål University Hospital, Oslo, Norway.
Karlsson
B R
BR
Torvik
A
A
D000328:Adult; D000368:Aged; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D016548:Prosencephalon; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism
D001798:Blood Proteins; D012709:Serum Albumin