HERPES-SIMPLEX VIRUS VECTORS OVEREXPRESSING THE GLUCOSE-TRANSPORTER GENE PROTECT AGAINST SEIZURE-INDUCED NEURON LOSS

We have generated herpes simplex virus (HSV) vectors vIE1GT and v alph a 4GT bearing the GLUT-1 isoform of the rat brain glucose transporter (GT) under the control of the human cytomegalovirus ie1 and HSV alpha 4 promoters, respectively, We previously reported that such vectors en hance glucose uptake in hippocampal cultures and the hippocampus. In t his study we demonstrate that such vectors can maintain neuronal metab olism and reduce the extent of neuron loss in cultures after a period of hypoglycemia, Microinfusion of GT vectors into the rat hippocampus also reduces kainic acid-induced seizure damage in the CA3 cell field. Furthermore, delivery of the vector even after onset of the seizure i s protective, suggesting that HSV-mediated gene transfer for neuroprot ection need not be carried out in anticipation of neurologic crises. U sing the bicistronic vector v alpha 22 beta gal alpha 4GT, which coexp resses both GT and the Escherichia coli lacZ marker gene, we further d emonstrate an inverse correlation between the extent of vector express ion in the dentate and the amount of CA3 damage resulting from the sim ultaneous delivery of kainic acid.