The effect of 4β-phorbol-12,13-dibutyrate and staurosporine on the extracellular glutamate levels during ischemia in the rat striatum

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Abstract

Hypothermia diminishes the ischemia-induced protein kinase C (PKC) translocation and inhibition, and also reduces transmitter release during ischemia. To study the role of PKC in the mechanism of glutamate release during ischemia, we measured extracellular glutamate levels in the striatum with the microdialysis technique, in the presence and absence in the dialysate of the PKC activator 4β-phorbol-12,13-dibutyrate (PDBu) and the protein kinase inhibitor staurosporine. We confirm that hypothermia attenuates the elevation of extracellular levels of glutamate in the striatum during ischemia. In the presence of PDBu, the glutamate levels in the dialysate increased from 0.3 μmol/L to an end ischemic level of 4.8 μmol/L during hypothermic ischemia (33°C). These levels were significantly higher than in hypothermic ischemia (33°C) without added PDBu. Staurosporine significantly mitigated the glutamate levels during normothermic ischemia. Our data suggest that PKC is involved in the temperature-dependent elevations of extracellular glutamate levels in the striatum during ischemia, and we propose that compounds preventing PKC activation may mimic the hypothermic protective action against ischemic brain damage.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
Forskningsområden

Nyckelord

Originalspråkengelska
Sidor (från-till)133-147
TidskriftMolecular and Chemical Neuropathology
Volym35
Utgåva nummer1-3
StatusPublished - 1998 aug
PublikationskategoriForskning
Peer review utfördJa