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.
Panizzon
K L
KL
Neuronal Injury Laboratory, Sepulveda VA Medical Center, CA 91343, USA.
Dwyer
B E
BE
Nishimura
R N
RN
Wallis
R A
RA
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D002534:Hypoxia, Brain / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008665:Metalloporphyrins; D018696:Neuroprotective Agents