Early expression of glutamate transporter proteins in ramified microglia after controlled cortical impact injury in the rat

Traumatic brain injury is followed by increased extracellular glutamate con centration. Uptake of glutamate is mainly mediated by the glial glutamate t ransporters GLAST and GLT-1. Extent and distribution of GLAST and GLT-1 wer e studied in a rat model of controlled cortical impact injury (CCH). Wester n Blot analysis revealed lowest levels of GLAST and GLT-1 with a decrease b y 40%-54% and 42%-49% between 24 and 72 h posttrauma. By 8 h after CCll, CS F glutamate levels were increased (10.5 muM vs. 2.56 VM in controls; P < 0. 001), reaching maximum values by 48 h. A significant increase in de novo GL AST and GLT-1 expressing ramified microglia was observed within 4 h, reache d a stable level by 48 li, and remained high up to 72 h after CCH. Furtherm ore, ramified microglia de novo expressed the neuronal glutamate transporte r EAAC1 after CCII Following CCII, GLAST/GLT-1 and GFAP coexpressing astroc ytes were immediately reduced, reaching minimum levels within 8 h. This red uction of expression could be either due to protein downregulation or loss of astrocytes. At 72 h, a marked population of GLAST- and GLT-1-positive re active astrocytes appeared. These results support the hypothesis that reduc ed astrocytic GLAST and GLT-1 protein levels following MI contribute to evo lving secondary injury. Microglia are capable of de novo expressing glutama te transporter proteins, indicating that the expression of glial and neuron al glutamate transporters is not restricted to a specific glial or neuronal lineage. Ramified microglia may play an important compensatory role in the early regulation of extracellular glutamate after CCII. (C) 2001 Wiley-Lis s, Inc.