Changes of metabolite profile in kainic acid induced hippocampal injury in rats measured by HRMAS NMR

Abstract

The solid-state high resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) technique was applied in this work to characterize and quantify the neurochemical changes in the rat hippocampus (CA1 or CA3) after local administration of kainic acid (KA). Intact tissue samples obtained from the KA treated and control brain samples were analyzed using HRMAS NMR. Metabolite profiles from NMR spectra of KA treated and control samples revealed the statistical significant decrease of N-acetylaspartate (NAA) and an increase of choline derivatives in the CA1 and CA3 directly receiving KA injection. Less extensive KA-induced metabolic changes were found in the hippocampi sample from the area contralateral to the site receiving KA administration. These results provided quantitative metabolic information on KA-induced neuronal loss and cell breakdown. In addition, the present study also revealed increased level of gamma-aminobutyric acid (GABA) and glutamate after KA treatment, suggesting that the cellular release of inhibitory and excitatory amino acids can be quantified using this method. KA induced microglia activation was evidenced by increased level of myo-insitol (myo-I). This study demonstrates that ex vivo HRMAS NMR is a useful tool for analyzing and quantifying changes of neurochemistry and cerebral metabolism in the intact brain.