Objective To investigate the protective effects and mechanisms of N-acetylcysteine (NAC) as an antioxidant in ischemia-reperfusion injury in the mouse brain. Methods Mice were randomly divided into 3 groups: sham group, model group and NAC group (150 mg/kg), with 18 mice in each group. The model and NAC groups underwent middle cerebral artery occlusion (MCAO) followed by reperfusion, while the sham group underwent the same procedure without vessel occlusion. The NAC group received an intraperitoneal injection of NAC (150 mg/kg) immediately after reperfusion, whereas the sham and model groups received an equal volume of 0.9% sodium chloride solution. Neurological function was evaluated by behavioral tests 24 hours after reperfusion. Cerebral blood flow was assessed using laser speckle contrast imaging. Infarct volume was detected by 2,3,5-triphenyltetrazolium chloride staining. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured by ELISA. Reactive oxygen species (ROS) levels in brain tissue were detected using ROS fluorescent probes. The expression and colocalization of NeuN, Nrf2, and HO-1 proteins in brain tissue were examined by immunofluorescence. The protein levels of Nrf2 and HO-1 in brain tissue were analyzed by Western blot. Results NAC significantly reduced neurological function scores, increased cerebral blood flow, decreased infarct volume, elevated SOD levels, and reduced MDA content. The rate of NeuN-positive cells increased, and ROS levels decreased. The protein levels of Nrf2 and HO-1 increased (P<0.05), and Nrf2 and HO-1 colocalized with NeuN. Conclusions NAC effectively alleviates cerebral ischemia-reperfusion injury in mice, attenuates oxidative stress, and rescues damaged neurons, potentially through modulation of Nrf2/HO-1 signaling pathway.
Key words
N-acetylcysteine /
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Cerebral ischemia-reperfusion /
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Oxidative stress /
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Nrf2/HO-1 signaling
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