Neuroprotective Effects of N-Acetyl-Cysteine in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial Publisher



Mehrpooya M¹ ; Mirzaasgari Z² ; Ahmadabad RA³ ; Farasati M⁴ ; Sahraei Z⁵ ; Khah PK⁶ ; Eshraghi A⁷ Show Affiliations
Source: Current Drug Therapy Published:2025

Abstract

Background: Acute ischemic stroke (AIS) represents a significant global health challenge leading to neuronal injury and functional impairment. The current therapeutic approaches primarily focus on restoring cerebral blood flow; however, they often fall short of preventing secondary neuronal damage and promoting recovery. N-Acetyl-Cysteine (NAC), a well-known antioxidant and glutathione precursor, has garnered attention for its potential neuroprotective properties in various neurological disorders. Hence, the primary objective of this study was to investigate the possible therapeutic effect of NAC in patients with AIS. Methods: The study employed a double-blind controlled trial methodology. A total of 62 patients using the online platform www.sealedenvelope.com, with participants in the intervention group being assigned following the generated sequence, were included in the study. Thirty-one patients were allocated to each of the two arms. The intervention group was administered NAC infusions (100 mg/kg initially and then 10 mg/kg per hour for 10 hours) in conjunction with their standard AIS treatment. The patients allocated to the control group were treated with the standard AIS treatment. The Matrix Metalloproteinase 9 (MMP-9, a biomarker of tissue destruction and blood-brain barrier (BBB) dysfunction) was measured in the two groups before and 24 hours after the administration of NAC. The National Institutes of Health Stroke Scale (NIHSS) was calculated for both groups before therapy, 24 hours after, and at 2 weeks, 1 month, and 3 months after therapy. These data were then compared with the serum levels of MMP-9 to evaluate the efficacy of the treatment in terms of tissue destruction and BBB dysfunction. Results: NIHSS scores for the intervention and control groups on admission were 6.87±4.15 and 8.11 ± 4.12 (p-value = 0.231), respectively. At 24 hours post-admission, the mean NIHSS score for the intervention group was 4.52±3.82, while that for the control group was 5.87 ± 4.36 (p-value=0-001). At two weeks post-admission, the mean NIHSS was 2.74 ± 0.60 in the intervention group and 5.33 ± 1.26 in the control group (p-value = 0.001). One month later, the mean NIHSS was 5.87 ± 1.59 in the intervention group and 2.12± 0.46 in the control group (p-value = 0.001). The mean NIHSS was 1.63 ± 0.49 and 3.33 ± 0.69 three months later (p-value = 0.001), which were statistically significant. The relationship between MMP9 and NIHSS was evaluated. No notable correlation was discerned between MMP9 alterations and the presence of neurological deficits at any of the specified time points. A reduction in the amount of MMP9 was observed in both the intervention and control groups 24 hours after injection. However, no statistically significant difference was identified between the groups. This indicates that the decline in MMP9 levels was not attributable to the administration of NAC. Conclusion: The administration of NAC was observed to result in a reduction in the severity of stroke-related symptoms and an improvement in neurological function and deficits among patients with AIS, in addition to the provision of standard therapy. This was in comparison to the control group. However, NAC could not significantly attenuate the elevated expression levels of MMP-9 after ischemia and reduce the damage of cerebral ischemia in patients with stroke. © 2025 Bentham Science Publishers.