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Updated: Jul 2, 2026
A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats
Published on: November 6, 2019
R788 is Associated with Neuroprotective Effects in Experimental Ischemic Stroke Models via Modulation of the
Yong Yang1, Jing Wang2, Heng Zhou3
1Department of Neurosurgery, the First Affiliated Hospital of Yangtze University, the First People's Hospital of Jingzhou, Jingzhou, Hubei, 434000, People's Republic of China.
Background:
Ischemic stroke, the most prevalent form of cerebrovascular disease, stands as a leading global cause of both disability and mortality. Oxidative stress damage is a critical pathological mechanism in stroke, and regulated cell death may be an effective therapeutic target for treating ischemic stroke. This work provides the first evidence that R788, a small-molecule inhibitor of spleen tyrosine kinase, exerts therapeutic efficacy in ischemic stroke, thereby unveiling a novel mechanistic basis and potential strategy for intervention.
Methods:
The antioxidant defense and anti-apoptotic effects of R788 were assessed in a middle cerebral artery occlusion (MCAO) animal model and an H2O2-induced SH-SY5Y cell model of IS. A total of 24 male C57BL/6 mice were randomly divided into 4 groups (n=6). Then we measured the intracellular Fe2+ concentration and lipid peroxidation levels, and the expression of the STAT1/Nrf2/GPX4 pathway was evaluated in the MCAO animal model and the cell model.
Results:
The results showed that both in the animal and cell models, the R788-treated group had an increased number of surviving SH-SY5Y cells compared to the control group. Additionally, the R788 group showed the inhibition of p-STAT1 and suppressed ferroptosis. We confirmed that R788 treatment alleviated oxidative stress damage by inhibiting ferroptosis-related pathways, thereby promoting cell survival. In summary, R788 demonstrated neuroprotective effects against ischemia-induced neural injury in both in vivo and in vitro models.
Conclusion:
Our workss suggest that R788 alleviate localized ischemic injury and oxidative stress damage by regulating STAT1/Nrf2/GPX4 pathways. These findings indicate that R788 shows potential for the treatment of IS.