Role of Neuroexcitation in Maturation of Postischemic and Posttraumatic Injury

Summary

The involvement of neuroexcitatory mechanisms in the maturation of brain lesions was evaluated in three experimental models: (a) repetitive ischemia in gerbils, (b) cryogenic cortical injury in rats and gerbils, and (c) global ischemia in rats. Our studies provided three observations that support the involvement of neuroexcitatory mechanisms in the development of delayed postischemic or posttraumatic neuronal damage: (a) characteristic uptake of calcium into the swollen dendrites, (b) changes in the blood-brain barrier, associated with uptake of serum albumin into the neurons, similar in nature to that described following seizures, and (c) reduction in the latency of evoked potentials from the visual cortex adjacent to cryogenic lesions, the effect of which could be eliminated by MK-801 or reproduced by a direct application of glutamate to the exposed cortex.

Slow maturation of chronic neuronal injury was characterized histologically by loss of the Nissl substance, peripheral vacuolization of neuronal cytoplasm or hyperchromasia, and accentuated staining of neuronal processes. Rats sacrificed 1 year following global ischemia showed considerable neuronal survival in the CA1 sector of the hippocampus. Other regions affected by ischemia were characterized by the presence of altered but still viable neurons in addition to occasionally apparent cell loss.