title: Early cellular swelling during cerebral ischemia in vivo is mediated by excitatory amino acids released from nerve terminals.
abstract: This study demonstrates ischemic cellular swelling in vivo detected as changes in the concentration of 14C-sucrose pre-perfused into the extracellular space (ECS) as an ECS marker. Microdialysis was utilized as a means of perfusion and measurement of the extracellular concentration of 14C-sucrose ([14C-sucrose]e). Concomitant with an abrupt increase in [K+]e at 1-3 min following the ischemia induction, [14C-sucrose]e was also rapidly elevated. Since sucrose is not taken up by either cells or capillaries, the absolute amount of 14C-sucrose in the ECS must be unchanged. The increase therefore appears to represent a relative decrease in water volume in the ECS resulting from a movement of water into the cells, i.e. cellular swelling. Ca(2+)-free perfusate containing Co2+, which has been shown to block excitatory amino acid release during cerebral ischemia, significantly delayed the increase in [14C-sucrose]e and [K+]e. Kynurenic acid, a broad-spectrum antagonist of excitatory amino acids, administered in situ through the dialysis probe also significantly delayed the increase in [14C-sucrose]e and [K+]e. These findings indicate that the early cellular swelling occurring during cerebral ischemia is a result of massive ionic fluxes mediated by excitatory amino acids which are released by a Ca(2+)-dependent exocytotic process from the nerve terminals.
authors.affiliation: Division of Neurosurgery, UCLA School of Medicine 90024.
authors.forename: Y
authors.initials: Y
authors.lastname: Katayama
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: D P
authors.initials: DP
authors.lastname: Becker
authors.forename: T
authors.initials: T
authors.lastname: Tsubokawa
mesh_terms: D000596:Amino Acids / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D003956:Dialysis; D007736:Kynurenic Acid / Q000494:pharmacology*; D009411:Nerve Endings / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D000596:Amino Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D003035:Cobalt; D007736:Kynurenic Acid; D002118:Calcium