Early cellular swelling during cerebral ischemia in vivo is mediated by excitatory amino acids released from nerve terminals.
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.
Katayama
Y
Y
Division of Neurosurgery, UCLA School of Medicine 90024.
Tamura
T
T
Becker
D P
DP
Tsubokawa
T
T
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
D000596:Amino Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D003035:Cobalt; D007736:Kynurenic Acid; D002118:Calcium