Calcium accumulation by glutamate receptor activation is involved in hippocampal cell damage after ischemia.
Rats exposed to 10 min of complete cerebral ischemia develop necrosis of the CA-1 region of the hippocampus after 2-3 days. We studied the involvement of synaptic transmission for this process by ablation of the afferent input (which is mainly glutamatergic) to CA1 by bilateral destruction of CA-3 neurons (Schafferotomi). The deafferentiation completely prevented the ischemic nerve cell destruction as revealed by histological studies after 6 days. The role of intracellular Ca++ overload was assessed by measurement of the interstitial Ca++ concentration. In control animals the interstitial Ca++ concentration decreases abruptly to 10% of the initial value 1.6 min after the onset of ischemia. The denervated hippocampi, however, showed no decrease during the 10 min of ischemia and hippocampi injected with 2-amino-5-phosphovalerate (APV), a competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptors, displayed a significantly reduced decrease (45% of the initial value) during ischemia. It is concluded that calcium influx via the glutamate-operated channels during the ischemic period is an important link in the development of ischemic brain cell damage.
Benveniste
H
H
Institute of Neuropathology, University of Copenhagen, Denmark.
Jørgensen
M B
MB
Diemer
N H
NH
Hansen
A J
AJ
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D007608:Kainic Acid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; D014633:Valine; D007608:Kainic Acid; D002118:Calcium