Heat stroke alters hippocampal and cerebellar transmitter metabonomics

Abstract

BACKGROUND:The mechanisms underlying heat stroke (HS)-induced hippocampal injury remain unclear. This study aimed to evaluate the HS-induced metabonomics of hippocampal and cerebellar transmitters. METHODS:The HS model was established with male Sprague-Dawley rats subjected to heat exposure of up to 42 °C at a humidity of (55.0±5.0)%. The hippocampal and cerebellar transmitters and metabolites of rats were tested via ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The primary transmitters and metabolites were identified by principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). The major metabolic pathways for HS were selected after enrichment. The brain injury was evaluated by histological tests.RESULTS: HS induced hippocampal and cerebellar injuries in rats. HS upregulated the protein levels of hippocampal glutamate, glutamine, gamma-aminobutyric acid, L-tryptophan (Trp), 5-hydroxy-indoleacetic acid, and kynurenine; however, it downregulated asparagine, tryptamine, 5-hydroxytryptophan, melatonin, 3,4-dihydroxyphenylalanine (L-DOPA), and vanillylmandelic acid. HS also sharply elevated the protein levels of cerebellar methionine and Trp, and decreased the levels of serotonin, L-alanine, L-asparagine, L-aspartate, cysteine, norepinephrine, spermine, spermidine, and tyrosine. Hippocampal glutamate, monoamine transmitters, cerebellar aspartate acid, and catecholamine transmitters' metabolic pathways were identified as the main metablic pathways in HS. CONCLUSION:The hippocampus and cerebellum were injured in rats with HS, possibly induced the disorder of hippocampal glutamate and serotonin metabolism, cerebellar aspartate acid and catecholamine transmitter metabolism, and related metabolic pathways.

INFLUENCES OF HEAT STRESS ON GLUTAMATE TRANSMISSION-DEPENDENT EXPRESSION LEVELS OF IL-1β and IL-18 IN BV-2 MICROGLIAL CELLS

“…Heat stress is a critical condition that can lead to cerebral injury and cognitive impairment, even in survivors (11). This severe condition is mainly accompanied by the release of numerous inflammatory factors and organ dysfunction.…”

“…Subsequent analysis of metabolic pathway enrichment and the KEGG database underscored significant alterations in glutamate-related metabolic pathways. Immunohistochemistry results indicated remarkable microglia activation in the rat hippocampus, whereas liquid chromatography-mass spectrometer validated an amplified release of glutamate in the hippocampal tissue (11). Building upon this groundwork, the present study employed an HS model in microglial cells to investigate its impact on glutamate metabolism and the secretion of proinflammatory factors.…”