Lactate Ameliorates Kainic Acid-Induced Neuroinflammation and Cognitive Impairment via the Chemokine Signaling Pathway in Mice.

PURPOSE

Lactate, previously considered a metabolic waste product, has been shown to have neuroprotective potential. This study aims to investigate the impact of lactate intervention and its underlying mechanisms on epilepsy.

METHODS

HT22 cells were stimulated with glutamate to construct an excitotoxicity cell model. An acute epilepsy model was established in mice by kainic acid induction. The neuronal damage, microglial activation, inflammatory responses, and functional changes were determined by TUNEL assays, immunohistochemistry, quantitative real-time polymerase chain reaction and behavioral tests. The differentially gene expression and functional enrichment were analyzed with RNA sequencing.

RESULTS

The in vitro lactate intervention reduced the number of apoptotic cells, the release of inflammatory factors, and the expression of vesicular glutamate transporter 1. In mice with acute epilepsy, lactate treatment mitigated neuronal damage, microglial activation, and inflammatory responses in the hippocampus and ameliorated anxiety-like behavior and cognitive impairment.

CONCLUSION

Lactate exerts therapeutic effects on epilepsy through the chemokine signaling pathway. The neuroinflammation is an important contributor to cognitive impairment. Targeting inflammatory pathways is a promising strategy for improving the prognosis of epilepsy.