Abstract WP259: Metabolomic Analysis of Ischemic Brain Tissue to Explore Specific Metabolic Pathway Assosiated With Cerebral Ischemia

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Abstract

Objectives: We investigated metabolic profiles of brain tissue in middle cerebral artery occlusion (MCAO) model of rats to explore the specific changes associated with acute ischemia.

Methods: Focal cerebral ischemia was induced in rats using filament occlusion of the MCA. Tissue samples from the ischemic lesion were collected before and after ischemia(0, 30, 60, 120min, n=7-10). Sham operated rats were treated in the same way except MCAO (n=10). Water-soluble metabolites were extracted and analyzed using gas-chromatography/mass-spectrometry(GS/MS). The obtained data were analyzed by multivariate statistics to explore metabolic pathways associated with ischemia. The associated metabolic enzymes were investigated with RT-PCR and Western blot.

Results: About ninety metabolites were identified by GC/MS. Principal component analysis and heatmap demonstrated clear separation between ischemia and control group (Figures). The most significant changes were decrease of fructose-6-phosphate and ribulose-5-phosphate, increase of hydroxybutyrate, and increase of GABA with time. These results suggested acceleration of pentose phosphate pathway to increase NADPH, upregulation of keton metabolism and neuroprotection by GABA. RT-PCR and Western blot did not indicate significant changes of transcription and protein level of the enzymes involved in these pathways and suggested changes of the enzyme activity by modification after transcription or translation such as phosphorylation.

Conclusions: These results suggested the presence of neuroprotective metabolic change in the ischemic brain.

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