Overexpression of the Glucose Transporter Gene with a Herpes Simplex Viral Vector Protects Striatal Neurons against Stroke

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Abstract
Herpes simplex virus vectors bearing a glucose transporter (GT) gene and a marker gene were found to protect neurons against a 1-h focal ischemic insult. Rats receiving the GT vector vα22βgalα4GT exhibited a 67.4 ± 35.3% survival of virally targeted neurons in the ischemic hemisphere compared with the contralateral control (n = 7), whereas rats receiving a control vector exhibited only 32.8 ± 17.9% survival (n = 9). This significant improvement in survival (105%, p = 0.022) suggests that energy failure is an important contributor to the neuropathology of ischemic damage in the striatum, and that it can be alleviated by gene transfer. This is the first demonstration of protection against ischemic cerebral injury by the direct transfer of GT genes to neurons.