Hypoxic neuronal damage in the absence of hypoxic depolarization in rat hippocampal slices: the role of glutamate receptors.
The propensity of neurons to undergo profound and precipitous depolarization is believed to contribute to their characteristic vulnerability to hypoxic injury. The length of time a neuron spends in a depolarized state following hypoxic depolarization (HD) is a critical determinant of the extent of irreversible cell damage. It is less clear, however, what the effects of moderate hypoxia are when HD does not occur. The present study examined the effects of prolonged, moderate hypoxia which does not elicit HD in rat hippocampal slices. Extracellularly-recorded population excitatory postsynaptic potentials (pEPSPs) in stratum radiatum of CA1 were eliminated 10-15 min after initiating hypoxia. Physiological damage was related to the hypoxic duration: full, intermediate, or poor recovery of pEPSP slope was observed after 30, 60, or 120 min of hypoxia, respectively. The glutamate receptor antagonists, D,L-2-amino-5-phosphonovaleric acid (APV) or 6,7-dinitroquinoxaline-2,3-dione (DNQX), enhanced the post-hypoxic recovery of synaptic responses. These findings demonstrate that profound HD is not necessary to elicit physiological damage during moderate hypoxia; moreover, the neuroprotective actions of excitatory transmitter antagonists are not limited to their capacity to delay HD. The precise characterization of cellular responses under these conditions will be of particular importance for understanding the pathophysiology of an ischemic penumbra.
Chen
Z F
ZF
Department of Neurological Surgery, University of Virginia, Charlottesville 22908, USA.
Schottler
F
F
Arlinghaus
L
L
Kassell
N F
NF
Lee
K S
KS
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015687:Cell Hypoxia; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D011810:Quinoxalines; D017470:Receptors, Glutamate; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate