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To compare Vitamin D (Vit D) levels in children with epilepsy on valproate monotherapy with healthy controls. Methods: A meta-analysis performed on articles identified from PubMed and Web of Science online databases evaluated using National Institute of Health National Heart, Lung, and Blood Institute Study Quality Assessment Tools. Subgroup analyses and publication bias assessments were also performed. Results: Eleven publications were eligible based on inclusion/exclusion criteria for the meta-analysis. Results noted a decrease in the mean Vit D level in children with epilepsy on valproate monotherapy compared with healthy children with a Standard Mean Difference = -0.313 [-0.457, -0.169]. Cumulative meta-analysis showed progressive negative effect of valproate therapy on Vit D levels across time. Other antiepileptic medications caused a similar effect on Vit D status. There was no evidence of publication bias in the analyses. Type of study design and country of origin introduced heterogeneities into the meta-analyses. Conclusion:This meta-analysis provides evidence that long-term therapy with valproate causes a decrease in Vit D levels in children. Therefore, in children with a seizure disorder on long-term valproate therapy, 25-OH-Vit D levels should be monitored and appropriate supplementation implemented if levels are deficient.

Vincristine (VCR), an alkaloid isolated from vinca, is a commonly used chemotherapeutic drug. However, treatment with VCR can lead to dose-dependent peripheral neurotoxicity, mainly manifesting as neuropathic pain, which is one of the dominant reasons for limiting its utility. Experimentally, we discovered that VCR-induced neuropathic pain was accompanied by astrocyte activation; the upregulation of p-CaMKII, Cav3.2, and Cx43 expression; and the production and release of in ammatory cytokines and chemokines in the spinal cord. Similar situations were also observed in astrocyte cultures.Interestingly, these alterations were all reversed by intrathecal injection of KN-93 (a CaMKII inhibitor) or L -Ascorbic acid (a Cav3.2 antagonist). In addition, KN-93 and L -Ascorbic acid inhibited the increase in [Ca 2+ ] i associated with astrocyte activation. We also veri ed that inhibiting and knocking down Cx43 levels via intrathecal injection of Gap27 and Cx43 siRNA relieved pain hypersensitivity and reduced the release of in ammatory factors; however, they did not affect astrocyte activation or p-CaMKII and Cav3.2 expression. The overexpression of Cx43 through the transfection of the Cx43 plasmid did not affect p-CaMKII or Cav3.2 expression in vitro. Therefore, CaMKII and Cav3.2 may activate astrocytes by increasing [Ca 2+ ] i , thereby mediating Cx43-dependent in ammation in VCR-induced neuropathic pain. Moreover, we demonstrated that the CaMKII signalling pathway was involved in VCR-induced in ammation, apoptosis, and mitochondrial damage. In summary, our ndings show a novel mechanism by which CaMKII and Cav3.2 mediate Cx43-dependent in ammation by activating astrocytes in neuropathic pain induced by VCR.