NEUROPROTECTION AGAINST CA1 INJURY WITH METALLOPORPHYRINS

THE hippocampal slice was used to examine neuroprotection with metallo porphyrins, a class of drug which inhibits heme oxygenase and which ha s been found to be effective in the treatment of neonatal hyperbilirub inemia. Tin-protoporphyrin given during hypoxia significantly improved recovery of CA1 antidromic PS to a mean of 82 +/- 2% of initial ampli tude, while unmedicated slices regained only 6 +/- 3% of initial ampli tude. Tin-protoporphyrin also protected against fluid percussion injur y with an EC(50) Of 10 mu M when given after trauma. This protection e xtended to induction of long-term potentiation. Tin-mesoporphyrin and zinc-protoporphyrin protected against trauma with EC(50)'s of 4 and 32 mu M. Treatment with Sn-PP also protected against exposure to hydroge n peroxide, but not NMDA, AMPA, glycine or nitric oxide. These finding s indicate that metalloporphyrins protect against CA1 neuronal injury through direct neural effects.