Ischemic neuronal injury appears to be mediated by disruption of subcellular ion distribution and, therefore, prevention of ion relocation might be neuroprotective. X-ray microanalysis was used to measure concentrations of Na, K, Ca and other elements in subcellular compartments (e.g., mitochondria) of CA1 neurons from oxygen/glucose-deprived (OGD) hippocampal slices. Results showed that OGD produced progressive loss of ion regulation in CA1 cells. Post-OGD reperfusion with normal media exacerbated the initial ion deregulation. To study neuroprotective mechanisms, we determined the ability of hypothermia (31°C) or ion channel blockade to retard intraneuronal ion disruption induced by OGD/reperfusion. Whereas Ca2+ channel blockade (ω-conotoxin MVIIC, 3 μM) was ineffective, hypothermia and Na+ channel blockers (tetrodotoxin, TTX, 1 μM; lidocaine, 200 μM) reduced ion deregulation in subneuronal compartments. Blockade of glutamate receptors (AMPA, 10 μM; the non-NMDA receptor antagonist CNQX, 10 μM/100 μM glycine; the NMDA receptor antagonist CCP, 100 μM) during OGD/reperfusion provided nearly complete protection. These findings provide a foundation for identifying potential pharmacotherapeutic approaches and for discerning corresponding mechanisms of neuroprotection.
|Original language||English (US)|
|Number of pages||13|
|Journal||Annals of the New York Academy of Sciences|
|State||Published - 1999|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science