Absence of Delayed Neuronal Death in ATP-Injected Brain: Possible Roles of Astrogliosis

ABSTRACT

Although secondary delayed neuronal death has been considered as a therapeutic target to minimize brain damage induced by several injuries, delayed neuronal death does not occur always. In this study, we investigated possible mechanisms that prevent delayed neuronal death in the ATP-injected substantia nigra (SN) and cortex, where delayed neuronal death does not occur. In both the SN and cortex, ATP rapidly induced death of the neurons and astrocytes in the injection core area within 3 h, and the astrocytes in the penumbra region became hypertropic and rapidly surrounded the damaged areas. It was observed that the neurons survived for up to 1-3 months in the area where the astrocytes became hypertropic. The damaged areas of astrocytes gradually reduced at 3 days, 7 days, and 1-3 months. Astrocyte proliferation was detectable at 3-7 days, and vimentin was expressed in astrocytes that surrounded and/or protruded into the damaged sites. The NeuN-positive cells also reappeared in the injury sites where astrocytes reappeared. Taken together, these results suggest that astroycte survival and/or gliosis in the injured brain may be critical for neuronal survival and may prevent delayed neuronal death in the injured brain.