Vitamin D, a novel treatment for intracerebral hemorrhage: a preclinical study

Abstract

Objective: Intracerebral hemorrhage (ICH) is second deadly CNS diseases with high mortality rate up to 60%. Current treatments for ICH are limited in therapeutic significant and resulted in poor prognosis. Studies in recent decades revealed that Vitamin D (Vit D) would significantly benefit in ischemic stroke. However, actions of Vit D in ICH have yet been explored. Our study is aimed to fill this knowledge gap. Method: We employed a standardized collagenase-induced ICH model in male mice. 1000IU/kg/day of Vit D were given to post-ICH mice orally with Vit D normal and Vit D deficient status for 4 weeks. To evaluate the therapeutic effects of vitamin D in ICH, three neurofunctional assessments were performed every 7 days after ICH. Underline pathophysiological mechanisms in neuronal survival, astrogliosis and myelination were investigated with histology and western blot. Result: Overall, significantly better functional outcomes were achieved with Vit D treatment mice. We recorded that higher mortality in Vit D deficient group and measured with 12% larger in hematoma volume. Immunohistological staining to the brain slides on 28th day: (i) more survived neurons and less reactive astrocytes were found in the peri-lesion area in Vit D treatment group; (ii) higher expression level of neuronal myelination markers were found in Vit D treatment. Western bolt studies confirmed the above findings. Conclusion: These results indicate that Vit D may serve as neuroprotective agent in promoting neurofunctional recovery after ICH. Actions of Vit D in ICH are: (i) promoted neuronal survival; (ii) reduced proliferation of reactive astrocytes; (iii) enhanced neuronal myelination.