Glutamate transporter EAAT4 is increased in hippocampal astrocytes following lateral fluid-percussion injury in the rat.

Functional impairment of glutamate transporters contributes to excitotoxic damage and exacerbation of injury in certain neurodegenerative disorders. Several high-affinity sodium-dependent glutamate transporters have been cloned thus far. Of these, EAAT4 is abundantly expressed in Purkinje cells of the cerebellum in rats. However, little is currently known regarding levels of EAAT4 following traumatic brain injury (TBI). In this study, EAAT4 changes were examined for up to 7 days after moderate fluid-percussion by immunoblotting and immunohistochemistry. TBI caused a 20% and 25% increase in EAAT4 levels in the injured hippocampus at day 3 and day 7 following the insult. Immunohistochemical analysis revealed this increase to be localized in cells exhibiting morphological characteristics of astrocytes. In addition, increased EAAT4 immunoreactivity was observed in astrocytes in the ipsilateral cortex and cerebellum at day 3 post-injury that persisted up to 7 days after the insult. Given the reported novel characteristics of chloride conductance displayed by this transporter, our findings of increased EAAT4 levels suggest this protein may play an important role in the pathophysiology of TBI.