OVER-EXPRESSION OF HSP-7O PROTECTS ASTROCYTES FROM COMBINED OXYGEN-GLUCOSE DEPRIVATION

Pretreatment by a sublethal insult is associated with induction of str ess proteins and with protection from subsequent injury. Heat pretreat ment protects the brain from subsequent ischemia, and is shown here to protect primary astrocyte cultures from subsequent oxygen-glucose dep rivation. To determine whether the expression of a single stress prote in, HSP-70, could account for much of this protection, we expressed HS P-70 or beta-galactosidase in astrocytes using retroviral vectors. Onl y 12% of astrocytes expressing HSP-70 died after 7 hours of oxygen-glu cose deprivation compared to 65% of astrocytes expressing beta-galacto sidase and 82% of normal astrocytes. Our data provide direct evidence that selective expression of HSP-70 enhances the survival of astrocyte s challenged with heat or oxygen-glucose deprivation.