Neuronal death by repetitive cortical spreading depression in juvenile rat brain.

Spreading depression (SD) is an intrinsic bioelectrical property of the human central nervous system, which plays a key role in neurological disorders. In the present study, we investigated whether experimentally induced repetitive SD caused neuronal death in cortical and subcortical regions of the juvenile rat brain. The animals were anesthetized and the electrodes as well as a cannula were implanted over the brain. Repetitive cortical SD events were induced by KCl injection. The brains were removed after 4 weeks. Repetitive SD enhanced the production of dark neurons, reduced the mean volume of normal neurons, increased the number of apoptotic neurons, and enhanced expression of the NR(2B) subunit of NMDA receptors as well as the GluR1 subunit of AMPA receptors in various regions of the juvenile rat brain. In addition, induction of repetitive SD enhanced long-term potentiation in CA1 hippocampal area. We observed a correlation between cell injury/neuronal death induced by repetitive SD and changes in glutamate receptor expression. The data indicate that repetitive cortical SD in juvenile rats causes neuronal damage in both cortical and subcortical areas of the brain. This may play an important role in the pathophysiology of SD-related neurological disorders, especially in children.