Abstract:Background: Acute ischemic stroke is one of the most important factors leading to disability and death with the characterization of accumulated neuron death and injured supportive neurovascular structures. Raf-1 kinase inhibitory protein (RKIP) is a key molecule in cell response to survival or death stimuli. However, the role of RKIP in stroke is worthy to be further studied. Methods: We used lentivirus mediated RKIP knockdown and overexpression to investigate the effect of RKIP on animal models of focal cereb… Show more
“…Peroxynitrite permeates lipid layers, with peroxidation of membrane lipids, mediating nitration of tyrosine residue, inhibiting tyrosine phosphorylation, and thereby affecting cellular signal transduction. 51 Downregulation of PEBP and concomitant dementia was reported in rat brain samples exposed to hypoxia. 45 In the current study, combined use of LEV and WJ-MSCs was the most effective regimen as regard infarction volume and functional memory test.…”
In the brain ischemia model, combined WJ-MSCs and LEV have demonstrated striking protective effects in brain infarction by the modulation of the oxidant status and neuroprotective effect.
“…Peroxynitrite permeates lipid layers, with peroxidation of membrane lipids, mediating nitration of tyrosine residue, inhibiting tyrosine phosphorylation, and thereby affecting cellular signal transduction. 51 Downregulation of PEBP and concomitant dementia was reported in rat brain samples exposed to hypoxia. 45 In the current study, combined use of LEV and WJ-MSCs was the most effective regimen as regard infarction volume and functional memory test.…”
In the brain ischemia model, combined WJ-MSCs and LEV have demonstrated striking protective effects in brain infarction by the modulation of the oxidant status and neuroprotective effect.
“…Studies have indicated that inflammatory response runs through the pathological development of cerebral ischemia-reperfusion and is one of the main causes of neuronal death [ 38 ]. Elevated proinflammatory cytokines aggregate a large number of inflammatory cells which secrete excessive inflammatory cytokines and aggravate brain damage [ 39 ].…”
Background. Cerebral ischemic stroke is a refractory disease which seriously endangers human health. Remote ischemic perconditioning (RiPerC) by which the sublethal ischemic stimulus is administered during the ischemic event is beneficial after an acute stroke. However, the regulatory mechanism of RiPerC that relieves cerebral ischemic injury is still not completely clear. Methods. In the present study, we investigated the regulatory mechanism of RiPerC in a rat model of ischemia induced by the middle cerebral artery occlusion (MCAO). Forty-eight adult male Sprague-Dawley (SD) rats were injected intracerebroventricularly with miR-98 agomir, miR-98 antagomir, or their negative controls (agomir-NC, antagomir-NC) 2 h before MCAO or MCAO+RiPerC followed by animal behavior tests and infraction volume measurement at 24 h after MCAO. The expression of miR-98, PIK3IP1, and tight junction proteins in rat hippocampus and cerebral cortex tissues was detected by quantitative polymerase chain reaction (qPCR) and Western blot (WB). Enzyme-linked immunosorbent assay (ELISA) was used to assess the IL-1β, IL-6, and TNF-α levels in the rat serum. Results. The results showed that in MCAO group, the expression of PIK3IP1 was upregulated, but decreased after RiPerC treatment. Then, we found that PIK3IP1 was a potential target of miR-98. Treatment with miR-98 agomir decreased the infraction volume, reduced brain edema, and improved neurological functions compared to control rats. But treating with miR-98 antagomir in RiPerC group, the protective effect on cerebral ischemia injury was canceled. Conclusion. Our finding indicated that RiPerC inhibited the MCAO-induced expression of PIK3IP1 through upregulated miR-98, thereby reducing the apoptosis induced by PIK3IP1 through the PI3K/AKT signaling pathway, thus reducing the cerebral ischemia-reperfusion injury.
“…Nuclear‐κB is the major nuclear transcription factor, and its activation usually stimulates inflammatory signalling pathways in microglia. Activated microglia, with a high expression of NF‐κB, promote the formation of an inflammatory microenvironment and damage to neurons or oligodendrocytes (Cherry, Olschowka, & O'Banion, ; Murugan, Sivakumar, Lu, Ling, & Kaur, ; Su, Zhang, Chen, Zhu, & Ma, ). Furthermore, it has been reported that inflammatory cells play an important role in neurodegenerative diseases via release of various pro‐inflammatory molecules (Calabrese et al., ).…”
Section: Discussionmentioning
confidence: 99%
“…Nuclear-B is the major nuclear transcription factor, and its activation usually stimulates inflammatory signalling pathways in microglia. Zhu, & Ma, 2017). Furthermore, it has been reported that inflammatory cells play an important role in neurodegenerative diseases via release of various pro-inflammatory molecules (Calabrese et al, 2018).…”
New Findings
What is the central question of this study?Oligomeric proanthocyanidin has the capacity to alleviate abnormalities in neurological functioning. However, whether oligomeric proanthocyanidin can reduce the progression of demyelination or promote remyelination in demyelinating diseases remains unknown.
What is the main finding and its importance?Oligomeric proanthocyanidin can improve cuprizone‐induced demyelination by inhibiting immune cell infiltration, reversing overactivated microglia, decreasing the inflammatory cytokines secreted by inflammatory cells and decreasing the production of myelin oligodendrocyte glycoprotein35–55‐specific antibody in the brain.
Abstract
Demyelinating diseases of the CNS, including multiple sclerosis, neuromyelitis optica and acute disseminated encephalomylitis, are characterized by recurrent primary demyelination–remyelination and progressive neurodegeneration. In the present study, we investigated the therapeutic effect of oligomeric proanthocyanidin (OPC), the most effective component of grape seed extract, in cuprizone‐fed C57BL/6 mice, a classic demyelination–remyelination model. Our results showed that OPC attenuated abnormal behaviour, reduced demyelination and increased expression of myelin basic protein and expression of O4+ oligodendrocytes in the corpus callosum. Oligomeric proanthocyanidin also reduced the numbers of B and T cells, activated microglia in the corpus callosum and inhibited secretion of inflammatory factors. Furthermore, concentrations of myelin oligodendrocyte glycoprotein‐specific antibodies were significantly reduced in serum and brain homogenates after OPC treatment. Together, these results demonstrate a potent therapeutic effect for OPC in cuprizone‐mediated demyelination and clearly highlight multiple effects of this natural product in attenuating myelin‐specific autoantibodies and the inflammatory microenvironment in the brain.
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