Arginine is neuroprotective through suppressing HIF-1α/LDHA-mediated inflammatory response after cerebral ischemia/reperfusion injury

Mol Brain. 2020 Apr 22;13(1):63. doi: 10.1186/s13041-020-00601-9.

Abstract

Neuroinflammation is a secondary response following ischemia stroke. Arginine is a non-essential amino acid that has been shown to inhibit acute inflammatory reaction. In this study we show that arginine treatment decreases neuronal death after rat cerebral ischemia/reperfusion (I/R) injury and improves functional recovery of stroke animals. We also show that arginine suppresses inflammatory response in the ischemic brain tissue and in the cultured microglia after OGD insult. We further provide evidence that the levels of HIF-1α and LDHA are increased after rat I/R injury and that arginine treatment prevents the elevation of HIF-1α and LDHA after I/R injury. Arginine inhibits inflammatory response through suppression of HIF-1α and LDHA in the rat ischemic brain tissue and in the cultured microglia following OGD insult, and protects against ischemic neuron death after rat I/R injury by attenuating HIF-1α/LDHA-mediated inflammatory response. Together, these results indicate a possibility that arginine-induced neuroprotective effect may be through the suppression of HIF-1α/LDHA-mediated inflammatory response in microglia after cerebral ischemia injury.

Keywords: Arginine; HIF-1α; Ischemia stroke; LDHA; Neuroinflammation; Neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Arginine / therapeutic use*
  • Cell Death
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / pathology
  • Inflammation / pathology*
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Microglia
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotection
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Signal Transduction / drug effects

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neuroprotective Agents
  • Arginine
  • L-Lactate Dehydrogenase