Accumulation of calcium and loss of potassium in the hippocampus following transient cerebral ischemia: a proton microprobe study.
This study explored (a) whether postischemic accumulation of calcium in hippocampal neurons precedes or occurs pari passu with light microscopical signs of delayed neuronal necrosis, and (b) whether calcium initially accumulates in dendritic domains, presumed to have a high density of agonist-operated calcium channels. Transient ischemia of 10-min duration was induced in rats, and the animals were studied after 1, 2, 3, and 4 days of recovery. We measured total calcium and potassium contents in the stratum oriens, pyramidale, radiatum, and moleculare of the CA1 and CA3 sectors, using particle induced x-ray emission (PIXE) in the proton microprobe mode. The results showed significant accumulation of calcium and loss of potassium after 3 and 4 days of recovery in the CA1 sector, which developed neuronal necrosis, but not in the CA3 sector, which showed only occasional damage. In a few animals, calcium accumulation (and loss of potassium) was observed with no or only mild visible damage, but in the majority of animals the accumulation of calcium correlated to signs of neuronal necrosis. Since calcium accumulation was similar in all strata examined, the results failed to reveal preferential accumulation in dendritic or somal regions. Based on our results and those of Dux et al., we emphasize the possibility that delayed neuronal death is, at least in part, caused by increased calcium cycling of plasma membranes and gradual calcium overload of mitochondria.
Martins
E
E
Laboratory for Experimental Brain Research, Lund Hospital, University of Lund, Sweden.
Inamura
K
K
Themner
K
K
Malmqvist
K G
KG
Siesjö
B K
BK
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*; D011522:Protons; D013052:Spectrometry, X-Ray Emission
D011522:Protons; D011188:Potassium; D002118:Calcium