Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study

Abstract

Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection.

Effects of Vitamin C on the Prevention of Ischemia-Reperfusion Brain Injury: Experimental Study in Rats

“…Additionally, vitamin C has been linked to the reduction of ischemia-induced edema, the protection of cell death against neurotoxicity following ischemia, and the improvement of neuron's synaptic connection in cerebral ischemia [14]. In the current study, vitamin C was capable to reduce oxidative stress, which might partially explain its neuroprotective e ects on the CHS model developed.…”

“…Exogenous antioxidants such as ascorbic acid (vitamin C), α-tocopherol (vitamin E), β-carotene, resveratrol, and canabidiol may prevent ROS-induced neuronal cell damage and rapid consumption of endogenous antioxidant enzymes [11][12][13]. Vitamin C is an important antioxidant in brain metabolism, whose neuroprotective actions on reperfusion syndrome have been demonstrated [14,15]. Intraperitoneal injection of vitamin C was e ective when compared to either intravenous or oral administration, reaching a maximum concentration 60 min a er administration [16,17].…”

DHA Attenuates Hypoxia/Reoxygenation Injury by Activating SSeCKS in Human Cerebrovascular Pericytes

“…This increase in SSeCKS inhibited angiogenesis and provided endothelial cells with properties of the blood-brain barrier, significantly reducing human brain microvascular endothelial cell migration and capillary-like structure formation. DHA has been suggested to play an important role in alleviating the pathogenesis of ischemic brain injury by attenuating edema and neuronal loss and improving synaptic connection [22]. However, the effect of DHA in H/R-stimulated HBVPs and the relationship between DHA and SSeCKS are unclear.…”

Making Sense of Early High-dose Intravenous Vitamin C in Ischemia/Reperfusion Injury

“…Most preclinical studies investigated the effect of DHA on cerebral ischemia/reperfusion injury. In preclinical cerebral ischemia models in mice, rats and monkeys, DHA decreased mortality [42] and, in multiple studies, infarct size [42][43][44][45][46][47]. DHA administered 15 min, but also as late as 3 h post-ischemia produced a 6-to 9-fold reduction in infarct size, improved post-ischemic cerebral blood flow and decreased neurological impairment [42].…”