Glutamate transporters GLAST and EAAT4 regulate postischemic Purkinje cell death: an in vivo study using a cardiac arrest model in mice lacking GLAST or EAAT4.

Cerebellar Purkinje cells represent a group of neurons highly vulnerable to ischemia. Excitotoxicity is thought to be an important pathophysiological mechanism in Purkinje cell death following ischemia. The glutamate transporter is the only mechanism for the removal of glutamate from the extracellular fluid in the brain. Therefore, glutamate transporters are believed to play a critical role in protecting Purkinje cells from ischemia-induced damage. Two distinct glutamate transporters, GLAST and EAAT4, are expressed most abundantly in the cerebellar cortex. GLAST is expressed in Bergmann glia, whereas EAAT4 is concentrated in the perisynaptic regions of Purkinje cell spines. However, the in vivo functional significance of these glial and neuronal glutamate transporters in postischemic Purkinje cell death is largely unknown. To clarify the role of these glutamate transporters in the protection of Purkinje cells after global brain ischemia, we evaluated Purkinje cell loss after cardiac arrest in mice lacking GLAST or EAAT4. We found that Purkinje cells with low EAAT4 expression were selectively lost after cardiac arrest in GLAST mutant mice. This result demonstrates that GLAST plays a role in preventing excitotoxic cerebellar damage after ischemia in concert with EAAT4.