Study On The Influences Of γ-aminobutyric Acid On Cortical Spreading Depression In Vivo

Cortical spreading depression (CSD), a self-propagating depolarization wave of neuronal and glia, is implicated in many neurological disorders such as migraine, stroke, and epilepsy. GABA is the major inhibitory neurotransmitter in the central nervous system. Many components in the pathway of inhibitory synaptic transmission have been reported as potential therapeutic targets in treating neurological disorders. In this study, we studied the effect of GABA on the field potential and extracellular space diffusion parameters during acute CSD, and the mRNA and protein expressions for GAD65 and GAD67 following CSD. CSD was induced in vivo by concentrated potassium chloride. Application of GABAA receptor inhibitor pentylenetetrazol (PTZ) did not alter the amplitudes of the CSD-induced DC potential shifts but prolonged the CSD duration. Increased extracellular GABA content could reduce the extent of DC potential shifts during CSD. Exogenous GABA minimized the dynamic changes of the extracellular diffusion parameters ???extracellular volume fraction???and ? (diffusion tortuosity) during CSD, but PTZ didn't. Expressions of GAD65 and GAD67 were upregulated following CSD, but the upregulation was found mostly associated with neurons instead of astrocyte. It was suggested that increased GAD expression may be a self-initiated protective mechanism during CSD and GABA receptor may be a therapeutic target in treating CSD-related neurological disorders.