L-lactate preconditioning promotes plasticity-related proteins expression and reduces neurological deficits by potentiating GPR81 signaling in rat traumatic brain injury model

Brain Res. 2020 Nov 1;1746:146945. doi: 10.1016/j.brainres.2020.146945. Epub 2020 Jun 9.


Currently, there is no efficacious pharmacological treatment for traumatic brain injury (TBI). Previous studies revealed that L-lactate preconditioning has shown rich neuroprotective effects against cerebral ischemia, and therefore has the potential to improve neurological outcomes after TBI. L-lactate played a neuroprotective role by activating GPR81 in diseases of the central nervous system (CNS) such as TBI and cerebral ischemia. In this study we investigated the effects of L-lactate preconditioning on TBI and explored the underlying mechanisms. In this study, the mNSS test revealed that L-lactate preconditioning alleviates the neurological deficit caused by TBI in rats. L-lactate preconditioning significantly increased the expression of GPR81, PSD95, GAP43, BDNF, and MCT2 24 h after TBI in the cortex and hippocampus compared with the sham group. Taken together, these data suggested that L-lactate preconditioning is an effective method with which to recover neurological function after TBI. This reveals the mechanism of L-lactate preconditioning on TBI and provides a potential therapeutic method for TBI in humans.

Keywords: GPR81; L-lactate; Neurological function recovery; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain Injuries, Traumatic / metabolism*
  • Disease Models, Animal
  • Lactic Acid / pharmacology*
  • Male
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • GPR81 protein, rat
  • Neuroprotective Agents
  • Receptors, G-Protein-Coupled
  • Lactic Acid