Protective Effect of Nimodipine Against Valproic-acid Induced Biochemical and Behavioral Phenotypes of Autism

Abstract

Objective: Present study was designed to investigate behavioral and biochemical role of nimodipine in prenatal valproic acid (Pre-VPA) induced autism in rats. Methods: Valproic acid was utilized to induce autistic phenotypes in Wistar rats. The rats were assessed for social behavior. Hippocampus and prefrontal cortex (PFC) were utilized for various biochemical assessments, whereas cerebellum was used to assess blood brain barrier (BBB) permeability. Results: Pre-VPA rats showed reduction social interaction. Pre-VPA administration were decreased PFC levels of interleukin-10 (IL-10), and glutathione along with hippocampus cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF). Also, the animals have shown increase in PFC levels of IL-6, tumor necrosis factor-α, thiobarbituric acid reactive substance, Evans blue leakage and water content. Nimodipine countered Pre-VPA administered reduction in social interaction, CREB, BDNF, inflammation, oxidative stress, BBB permeability. Conclusion: Pre-VPA has induced autistic phenotype, which were attenuated by nimodipine in rats. Nimodipine and other calcium channel blockers should further investigate to check the management of autism.

The effect of triple reuptake inhibitor toludesvenlafaxine on neurological function in cerebral ischemic rats

“…Nimodipine has neuroprotective effects on many disorders of brain, such as subarachnoid hemorrhage, ischemic stroke, traumatic brain injury, and migraine (Kumar et al, 2022). Here, we used nimodipine as a positive control to observe the neuroprotective potential of Tdv.…”

Central Causation of Autism/ASDs via Excessive [Ca2+]i Impacting Six Mechanisms Controlling Synaptogenesis during the Perinatal Period: The Role of Electromagnetic Fields and Chemicals and the NO/ONOO(-) Cycle, as Well as Specific Mutations

“…Valproic acid has been shown to cause hepatotoxicity, especially in very young individuals [172]. Therefore, it may act to cause autism [67,[173][174][175] via hepatic encephalopathy, where liver toxicity leads to ammonia accumulation and excess ammonia acts to increase glutamatergic activity, including excessive NMDA-R activity. Ammonia does this via inhibition of the glutamate transporter, such that glutamate neurotransmission in the brain is excessive following valproic acid exposure.…”

“…Kumar et al [174] found that the VGCC calcium channel blocker nimodipine was useful in lowering both biochemical and behavioral effects in a valproic acid-induced autism rat model. The protocol they used was to induce autism by using a single injection of valproic acid at day 12.5 after conception and at 24 days after birth, to use I.P injection of nimodipine once a day.…”

“…The protocol they used was to induce autism by using a single injection of valproic acid at day 12.5 after conception and at 24 days after birth, to use I.P injection of nimodipine once a day. The valproic acid-induced biochemical changes that were greatly normalized by nimodipine included two markers of oxidative stress, three inflammatory cytokines, and changes in both CREB and BDNF activity [174]. The behavioral changes were also lowered by nimodipine, including three measures of social interactions [174].…”

“…The valproic acid-induced biochemical changes that were greatly normalized by nimodipine included two markers of oxidative stress, three inflammatory cytokines, and changes in both CREB and BDNF activity [174]. The behavioral changes were also lowered by nimodipine, including three measures of social interactions [174].…”