Neuroprotection against CA1 injury with metalloporphyrins.

The hippocampal slice was used to examine neuroprotection with metalloporphyrins, a class of drug which inhibits heme oxygenase and which has been found to be effective in the treatment of neonatal hyperbilirubinemia. Tin-protoporphyrin given during hypoxia significantly improved recovery of CA1 antidromic PS to a mean of 82 +/- 2% of initial amplitude, while unmedicated slices regained only 6 +/- 3% of initial amplitude. Tin-protoporphyrin also protected against fluid percussion injury with an EC50 of 10 microM when given after trauma. This protection extended to induction of long-term potentiation. Tin-mesoporphyrin and zinc-protoporphyrin protected against trauma with EC50's of 4 and 32 microM. Treatment with Sn-PP also protected against exposure to hydrogen peroxide, but not NMDA, AMPA, glycine or nitric oxide. These findings indicate that metalloporphyrins protect against CA1 neuronal injury through direct neural effects.