Improved posthypoxic recovery of synaptic transmission in gerbil neocortical slices treated with a calpain inhibitor.
OBJECTIVE
Among the various calcium-induced biologic events occurring in hypoxic neurons, activation of the calcium-activated neutral proteinase (calpain) is a likely mediator of neuronal degeneration. In this study, we assessed the protective effects of a calpain inhibitor (Cbz-Val-Phe-H) against hypoxic damage to the neocortex.


METHODS
An in vitro neocortical slice model from gerbils was used to study the delay to hypoxic depolarization during hypoxia and the recovery of synaptic responses after hypoxia. These responses were examined in control slices and slices treated with Cbz-Val-Phe-H.


RESULTS
The delay to hypoxic depolarization did not differ between treated and control groups. In contrast, synaptic recovery after a fixed period of hypoxia (15 minutes) was significantly improved in the Cbz-Val-Phe-H-treated slices (P < .01). Concentrations of Cbz-Val-Phe-H of 50 mumol/L or greater were significantly more protective than a concentration of 20 mumol/L (P < .01).


CONCLUSIONS
The data indicate that calcium-activated proteolysis plays a critical role in hypoxic damage to the neocortex and that calpain inhibitors may be useful therapeutic agents.
Hiramatsu
K
K
Department of Neurological Surgery, University of Virginia, Health Sciences Center, Charlottesville 22908.
Kassell
N F
NF
Lee
K S
KS
D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005849:Gerbillinae; D066298:In Vitro Techniques; D009435:Synaptic Transmission / Q000187:drug effects*
D004151:Dipeptides; D002154:Calpain; C058076:calpain inhibitor III