Sodium Dichloroacetate Stimulates Angiogenesis by Improving Endothelial Precursor Cell Function in an AKT/GSK-3β/Nrf2 Dependent Pathway in Vascular Dementia Rats

Abstract

Sodium dichloroacetate (DCA) is a mitochondrial pyruvate dehydrogenase kinase inhibitor, and has been shown to display vasoprotective effects in chronic ischemic stroke. The purpose of this study was to evaluate the therapeutic effect of DCA on vascular dementia (VD) and endothelial progenitor cell (EPC)-mediated angiogenesis. After cerebral ischemia-reperfusion in rats, DCA was administered continuously for 21 days; following which, histological analysis, and cognitive functional tests were conducted. Rat bone marrow-derived EPCs were isolated, their function and quantity were measured, and the effects of long-term administration of DCA on EPCs in a rat model of VD was studied. We found that long-term DCA administration improved cognitive function in VD rats, reduced brain infarct size and brain atrophy, increased VEGF and bFGF levels in vivo , promoted angiogenesis in damaged areas, and significantly improved EPC function in VD rats. Compared with the VD group, AKT, Nrf2, eNOS expression, and intracellular NO levels were elevated in EPCs of DCA-treated VD rats. In addition, GSK3β and intracellular ROS levels were decreased. Simultaneously, it was found that DCA directly acted on EPCs, and improved EPC functional behavior. Taken together, these findings suggested that long-term DCA administration improved cognitive function in a rat model of VD, and did so in part, by improving EPC function. Observations suggest that prolonged DCA administration might be beneficial in treating VD.

Tetrahydroxystilbene Glucoside Ameliorates Infrasound-Induced Central Nervous System (CNS) Injury by Improving Antioxidant and Anti-Inflammatory Capacity

“…Nissl's staining can show cellular necrosis [34] but not apoptosis. The increase in the number of Nissl bodies (chromatin granules) showed the reduction in neuronal necrosis [35]. Nissl staining demonstrated that the number of surviving neurons and Nissl bodies was lacking in the necrosis status of neurons [36].…”

Identification of Molecular Signatures and Candidate Drugs in Vascular Dementia by Bioinformatics Analyses

“…Increasing evidence has suggested that aberrant angiogenesis may play a role in the development of VaD, but its precise role remains controversial. A significant association between angiogenesis activity and cerebrovascular disease, which is a significant contributor to VaD, has been reported (Callahan et al, 2020), whereas other studies have indicated that promoting angiogenesis, especially in functional blood vessels, can reduce the extent of ischemia and improve cognition in VaD (Yang et al, 2017;Zhao et al, 2019). Clearly, more studies are needed to better understand the potential of angiogenesis as an intervention target.…”

Curcumin Derivative Cur20 Attenuated Cerebral Ischemic Injury by Antioxidant Effect and HIF-1α/VEGF/TFEB-Activated Angiogenesis

“…The major reason may be the ameliorated oxidative injuries, which was verified by results of ROS, MDA, SOD, and GSH in vivo. Although there are a series of pathophysiological changes after cerebral ischemia, oxidative stress is still one of the most serious strikes among Ca 2+ overload, excitatory amino acid overexpression, inflammatory response and so on (Zhao et al, 2019;Luca et al, 2015). During cerebral ischemia, mitochondrial function is abnormal with free radicals accumulation, which leads to lipid, protein, and DNA damage, causing apoptosis and irreversible necrosis.…”