NAC reduces hippocampal neuronal damage following transient global ischemia. - GreenMedInfo Summary
Neuroprotective effects of N-acetylcysteine via inhibition of matrix metalloproteinase in a mouse model of transient global cerebral ischemia.
Brain Res Bull. 2019 Nov 10. Epub 2019 Nov 10. PMID: 31722253
N-acetylcysteine (NAC) is known to serve many biological functions including acting as an antioxidant, and electing antiinflammatory effects. Previous reports have revealed that NAC may have neuroprotective effects against the deleterious effects of brain ischemia. Despite of this, the mechanism by which NAC prevents neuronal damage after brain ischemia remains unclear. The current study aimed to investigate this mechanism in a mouse model of transient global brain ischemia. In the present study, mice were subjected to 20 min of transient global brain ischemia, proceeded by intraperitoneal administration of NAC (150 mg/kg) in one group. The mice were then euthanized 72 h after this ischemic insult for collection of experimental tissues. The effect of NAC on neuronal damage and matrix metalloproteinase (MMP)-9activity were assessed and immunofluorescence, and hippocampal terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay experiments were conducted and results compared between NAC- and vehicle-treated groups. Neuronal damage was primarily observed in the hippocampal CA1 and CA2 regions. In NAC-treated mice, neuronal damage was significantly reduced after ischemia when compared to vehicle-treated animals. NAC also inhibited increased MMP-9 activity after global brain ischemia. NAC increased laminin and NeuN expression and inhibited increases in TUNEL-positive cells, all in the hippocampus. These results suggest that NAC reduces hippocampal neuronal damage following transient global ischemia, potentially via reductions in MMP-9 activity.