Sequential changes in glutamate transporter mRNA levels during Fe3+-induced epileptogenesis

Severe head injury in humans can cause recurrent seizures; this form of epi lepsy appears to correlate with the occurrence of parenchymal hemorrhage. T he injection of ferric cations, one component of hemoglobin, into rat amygd ala, causes lipid peroxidation, and recurrent spontaneous seizures. We wond ered whether the regulation of glutamate might be perturbed as a result of severe head injury, which might then act as a mechanism of chronic epilepto genesis. Levels of glutamate transporter glutamate-aspartate transporter (G LAST), glutamate transporter-1 (GLT-1), and excitatory amino-acid carrier ( EAAC-1) mRNA were measured in ipsilateral and contralateral hippocampi and cerebral cortex removed from rats at 60 min, 24 h, and 5, 15 and 30 days af ter FeCl3 injection into the amygdaloid body. While the neuronal transporte r EAAC-1 mRNA was elevated bilaterally for up to 30 days following the micr oinjection that initiated seizures, GLT-1 mRNA, derived from glial cells, r eturned to basal levels. At 15 and 30 days after injection, however, when t he experimental animals were experiencing spontaneous limbic;behavioral sei zures, GLAST mRNA was down-regulated. Epileptogenesis may correlate with th e impairment of glial glutamate transport, leading to an excitation and imb alance of transmitter influences within the hippocampi and cerebral cortex. (C) 2000 Elsevier Science B.V. All rights reserved.