||Ischemia can be induced by head trauma, stroke, and cardiac arrest. The causes are multifactorial, including hypoxia, nutrient deprivation and failure to remove toxic metabolic products. The injury of ischemic damage to neural cells is believed to be mediated by the excitotoxicity, calcium accumulation and free radical formation. Neurons are more vulnerable than astrocytes to ischemic damage. Brief exposure to ischemia does not cause severe injury to astrocytes and the responses of astrocytes are suggested to be beneficial to other neural cells in CNS. In this study, two in vitro models were used to study the changes of cellular responses and energy metabolism in cultured astrocytes under ischemia. By using the mineral oil induced ischemia model, c-Fos, c-Jun and the constitutively expressed form of HSP 70 proteins in cultured cortical astrocytes were induced by the injury of ischemia. They may act as specific markers for cortical astrocytes in response to ischemia. The anaerobic chamber induced ischemia model was used to study the alteration of energy metabolism in cortical neurons and astrocytes under ischemia. There was a direct correlation between the energy metabolism and cell injury in astrocytes under ischemia. The depletion of ATP in astrocytes was more tolerable than neurons to this simulated ischemic injury. The extent of damage to astrocytes by ischemia incubation was determined in this study. Two hour of ischemia did not cause any significant damage to astrocytes. Four hour of ischemia caused a moderate injury. By exposure to 6 and 8 hours of ischemia, the damage to cultured astrocytes became severe. Nine hour of ischemia was lethal to cultured astrocytes. The viable astrocytes after various lengths of ischemia incubations were able to retain their ability of ATP production. This study also suggested that the critical period for astrocytes in response to ischemia was between 4 to 6 hours. By studying the biochemical and molecular events of astrocytes around this period, it may provide essential information about the tolerance of astrocytes and assist in the development of potential therapies to prevent and cure the damage by ischemia.