Neuroprotective Effects of N-Acetyl-Cysteine in Patients with Acute Ischemic Stroke: A Randomized Controlled Trial
Authors: Mehrpooya Maryam , Mirzaasgari Zahra , Ahmadabad Rezan Ashayeri , Farasati Maryam , Sahraei Zahra , Khah Parnian Kheir , Eshraghi Azadeh 
Published: February 2025

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 strokerelated
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.