Blocking conversion of GABAergic inhibition as a potential mechanism of propofol-mediated brain protection following resuscitation.
Animal experiments and clinical studies have indicated that propofol pretreatment significantly improves post-resuscitation recovery of neuronal functions. However, current theories on how propofol enhances the inhibitory effects of gamma-aminobutyric acid (GABA) cannot fully explain its protective action on the brain. Recent studies have suggested that during the process of resuscitation, the effect of GABA is converted from inhibitory to excitatory, via a mechanism that is closely associated with activation of microglia and downregulation of the K(+)-Cl(-) cotransporter 2 (KCC2). We propose a hypothesis that propofol protects the brain through inhibiting the conversion of GABAergic inhibition into excitation during resuscitation. Activation of microglia, downregulation of KCC2, and correlations between these effects and the protective actions of propofol, may reveal the molecular mechanisms of propofol-mediated brain protection. Further investigations into the protective mechanisms of general anesthetics on the brain represented by propofol will help to guide rational clinical drug use, and will contribute to the discovery and development of novel brain-protective drugs to prevent perioperative cardiopulmonary resuscitation-associated brain injury.
Zhang
Hui
H
Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Mei
Xiaopeng
X
Wang
Wei
W
Sun
Xude
X
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009433:Neural Inhibition / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D027981:Symporters / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D015742:Propofol; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters