Abstracts

Rationale: Status epilepticus usually results in neuronal degeneration due to continuous excitatory insults to the susceptible neuronal population. Increased Ca2+ influx during seizure activities is considered a major cause of neuronal degeneration. The calpain family of calcium-activated neutral proteases is involved in neuronal physiology through the proteolytic modification of cytoskeletal and other proteins. However, excessive calpain activities can also lead to neuronal damage. Among cytoskeletal proteins, alpha II-spectrin is a major substrate for micro- and milli-calpains, and alpha II spectrin breakdown product (BDP) is a marker for prior calpain activity. To determine whether heightened calcium influx during status epilepticus excessively activates calpain with resultant neuronal degeneration, we performed immunohistochemistry for alpha II spectrin BDP on the cerebral sections of three patients who died after prolonged periods of status epilepticus. Methods: Immunohistochemistry was conducted with antibody against calpain-generated alpha II spectrin BDP. The antibody was made against a peptide (five amino acids) containing the sequence of the calpain cleavage site of alpha II spectrin. Five micron thick paraffin and 50 micron thick vibratome sections of the cerebral neocortex and hippocampus were subjected to immunohistochemical procedures utilizing the ABC method with either peroxidase or alkaline phophatase as the labeling enzyme. Results: Two cases showed many shrunken neurons with strong immunoreactivity for alpha II spectrin BDP in the hippocampus and neocortex. The third case revealed an almost complete loss of neurons in the hippocampal Sommer sector, and scattered neurons elsewhere were immunopositive. Occasional immunoreactive astrocytes were also noted. The marked neuronal immunopositivity observed in cases with status epilepticus was not demonstrated in three control cases without a history of convulsive disorders. Conclusions: The results suggest that the neuronal degeneration observed in status epilepticus is due, at least in part, to intense calpain activities following increased calcium influx.