Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, which
plays an important role in many aspects of normal brain function such as neural development, motor functions,
learning and memory etc. However, excessive accumulation of glutamate in the extracellular fluid will induce
excitotoxicity which is considered to be a major mechanism of cell death in brain ischemia. There is no enzyme to
decompose the glutamate in extracellular fluid, so extracellular glutamate homeostasis within the central nervous
system is mainly regulated by the uptake activity of excitatory amino acid transporters. Among the five excitatory
amino acid transporters, glial glutamate transporter-1 (GLT-1) is responsible for 90% of total glutamate uptake.
Thus, GLT-1 is essential for maintaining the appropriate level of extracellular glutamate, and then limiting excitotoxicity
of glutamate in central nervous system. Therefore, the regulation of GLT-1 might be a potential therapeutic
target for ischemic brain injury. This review summarizes recent advances including our findings in the methods
or medicine that could protect neurons against brain ischemic injury via upregulation of GLT-1 and discuss
the possible application of these strategies.
Keywords: Glutamate transporters, GLT-1, brain ischemia, preconditioning, cAMP, estrogen, histamine, dexamethasone, β-lactams
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