Vitamin D Activates Nrf2 to Prevent Nerve Injury and Reduce Brain Damage in Acute Cerebral Infarction

Abstract

Objective

This study aimed to investigate the neuroprotective effects of cholecalciferol cholesterol emulsion (CCE), a vitamin D (VD) precursor, in a murine model of acute cerebral infarction (ACI) and to elucidate the role of the Nrf2 signaling pathway in mediating these effects.

Methods

Forty C57BL/6J mice (male and female) were divided into five groups (n = 10 per group): control, control + CCE, ACI, ACI + CCE, and ACI + CCE + ML385 (an Nrf2 inhibitor). ACI was induced by middle cerebral artery occlusion (MCAO). CCE was administered for three weeks prior to ACI induction, and ML385 was administered intravenously to inhibit Nrf2. Neurological function, brain edema, and infarct size, as well as inflammatory and apoptotic marker levels, were assessed post-ACI. Statistical analyses were conducted via one-way ANOVA and Student's t test, with P < 0.05 considered significant.

Results

Compared to ACI group, CCE significantly reduced neurological deficits, brain edema, and infarct size (P < 0.01). The ACI + CCE group presented improved short-term memory retention, as evidenced by shorter avoidance latency in shuttle avoidance tests (P < 0.01). CCE administration attenuated the expression of inflammatory markers (IL-6, MIF, Lp-PLA2) while increasing IL-10 levels (P < 0.001). Furthermore, CCE increased Nrf2 and HO-1 expression and reduced apoptosis by decreasing the Bax/Bcl-2 ratio in brain tissue (P < 0.001). ML385 abolished these neuroprotective effects, confirming the role of the Nrf2 pathway in mediating the benefits of VD.

Conclusion

VD, via VD receptor-mediated activation of the Nrf2/HO-1 pathway, reduces inflammation, apoptosis, and neurological damage following ACI. These findings support the therapeutic potential of VD in the treatment of ischemic stroke and highlight the importance of Nrf2 in mediating these effects.

Keywords

Vitamin D / Acute cerebral infarction / Cholecalciferol cholesterol emulsion / Neuroprotection / Apoptosis / Nrf2 signaling pathway

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Funding

Medical Science Research Project Program of Hebei Province(20211722)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to Huazhong University of Science and Technology