Transcranial Direct-Current Stimulation Regulates MCT1-PPA-PTEN-LONP1 Signaling to Confer Neuroprotection After Rat Cerebral Ischemia–Reperfusion Injury
Xiangyi KongWenjie HuYu CuiJingchen GaoXujin YaoJinyang RenTao LinJiangdong SunYunyi GaoXiaohua LiHui WangHuanting LiFengyuan CheQi Wan
12
Citation
46
Reference
10
Related Paper
Citation Trend
Abstract:
Propionic acid (PPA) is a critical metabolite involved in microbial fermentation, which functions to reduce fat production, inhibit inflammation, and reduce serum cholesterol levels. The role of PPA in the context of cerebral ischemia-reperfusion (I/R) injury has yet to be clarified. Increasing evidence indicate that transcranial direct-current stimulation (tDCS) is a safe approach that confers neuroprotection in cerebral ischemia injury. Here, we show that the levels of PPA were reduced in the ischemic brain following a rat cerebral I/R injury and in the cultured rat cortical neurons after oxygen-glucose deprivation (OGD), an in vitro model of ischemic injury. We found that the decreased levels of transporter protein monocarboxylate transporter-1 (MCT1) were responsible for the OGD-induced reduction of PPA. Supplementing PPA reduced ischemia-induced neuronal death after I/R. Moreover, our results revealed that the neuroprotective effect of PPA is mediated through downregulation of phosphatase PTEN and subsequent upregulation of Lon protease 1 (LONP1). We demonstrated that direct-current stimulation (DCS) increased MCT1 expression and PPA level in OGD-insulted neurons, while tDCS decreased the brain infarct volume in the MCAO rats via increasing the levels of MCT1 expression and PPA. This study supports a potential application of tDCS in ischemic stroke.Keywords:
Brain ischemia
As a therapeutic strategy for ischemic stroke, neuroprotective agents are used to antagonize a series of harmful molecular biological events in cerebral ischemia. This article reviewes the current status of neuroprotective agents in the treatment of acute ischemic stroke, and the challenges from pre-clinical evidences translating into the clinical trials. The vascular endothelial cells, glial cells and neurons should be studied as a whole.
Key words:
Stroke; Brain ischemia; Neuroprotective agents
Stroke
Brain ischemia
Cite
Citations (0)
Ischemia is defined as cell death caused by insufficient perfusion of the tissue due to reduction in arterial or venous blood flow, depletion of cellular energy storages, and accumulation of toxic metabolites. The positive effects of controlled reperfusion are known and are used clinically. But the positive effects of controlled reperfusion on ovarian tissue have not been seen in the literature yet. The biochemical and histopathological comparative investigation of rat ovaries that were experimentally exposed to ischemia (IG), ischemia-reperfusion (I/R), and ischemia-controlled reperfusion (ICR) was aimed. Forty rats were divided into four groups (10 rats per group). First group: 3 h ischemia by vascular clips on ovarian tissue. Second group: 3 h ischemia + 1 h reperfusion. Third group: 3 h ischemia + 1 h controlled reperfusion (on-off method: controlled reperfusion by opening and closing the clips (on/off) in 10-second intervals, for 5 times for a total of 100 seconds). Fourth group: healthy rats. Biochemical (tGSH, MDA, and DNA damage level and SOD activity) and histopathological analysis were performed. The highest glutathione and superoxide dismutase measurements were found in ischemia/controlled reperfusion group among the ischemia or ischemia/reperfusion groups. Similarly the damage indicators (malondialdehyde, DNA damage level and histopathological damage grade) were the lowest in ischemia/controlled reperfusion group. These results indicate that controlled reperfusion can be helpful in minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia for various reasons (ovarian torsion, tumor, etc.).
Ovarian torsion
Malondialdehyde
Cite
Citations (35)
Objective: To study NF-κB and IL-6 expression in a rat retina that has been inj ured by ischemia-reperfusion and the effect of β-aescin on its expression.Methods: A retinal model of the rat retina for ischemia-reperfusion was establi s hed. 60 SD rats were divided into two groups: one was an ischemia-reperfusion g r oup and the other was an ischemia-reperfussion and β-aescin group. Each group wa s then divided into sub-groups according to the amount of time after ischemia- re perfusion:1 hour,6 hours,12 hours,24 hours,48 hours,and 72 hours. Each sub -group consisted of 5 rats. NF-κB mRNA and IL-6 mRNA in the rat retina was m easured by the ISH method. Each rat was examined by ERG before being sacrificed.Results: NF-κB and IL-6 began to express at 6 hours after ischemia-reperfusio n i n the ischemia-reperfusion group. The highest level of expression occurred 24 h o urs after injury. In the ischemia-reperfusion and β-aescin group,the NF-κB and IL-6 expressed at 12 hours after ischemia-reperfusion injury and reached the hi ghest level at 24 hours. However,its level was lower than the level for the isc hemia-reperfusion group at every stage(P0.05). The b wave of the ERG in the is chemia-reperfusion group was lower than that for the ischemia-reperfusion and β-aescin group at every stage(P0.05).Conclusion: NF-κB may induce IL-6 and play an important role in ischemia-reperfusion inj ury in the rat retina. The β-aescin may suppress NF-κB activity and protect the retina from injury caused by ischemia-reperfusion.
Erg
Rat model
Cite
Citations (0)
Effective efforts to screen for agents that protect against the devastating effects of stroke have not produced viable results thus far. As a result this article reviews the possible role of ethanol as a neuroprotective agent in stroke and traumatic brain injury (TBI). Previous studies have associated ethanol consumption with a decreased risk of ischemic stroke, suggesting a neuroprotective mechanism. The translation of this clinical knowledge into basic science research with the goal of new therapy for acute stroke patients remains in its initial stages. In a recent study involving rats, we have shown that ethanol administration, in the correct dose after stroke onset, protects against ischemia-induced brain injury. The purpose of this paper is to discuss ethanol’s neuroprotective properties in stroke when consumed as a preconditioning agent, in TBI with a positive blood alcohol content, and finally in stroke treatment, with the goal of using post-ischemia ethanol (PIE) therapy to ameliorate brain damage in the future. Keywords: Ethanol, alcohol, stroke therapy, ischemia/reperfusion injury, traumatic brain injury therapy, neuroprotection
Stroke
Brain ischemia
Cite
Citations (2)
Cite
Citations (239)
[Objective]To study the IL-6 express in rat's retina which injuried by ischemia-reperfusion and the effect of β-aescin on its expression. The model of rat's retina ischemia-reperfusion was employed. 60 SD rats were devided into two groups, one was ischemia-reperfusion group, the other was ischemia-reperfusion andβ-aescin group. Every group was devided into 1 hour, 6 hour, 12 hour, 24 hour, 48 hour and 72 hour groups. Every group had 5 rats. IL-6 mRNA was measured by ISH method in rat's retina. Every rat was examinated ERG before executed. IL-6 began to express at 6 hours after ischemia-reperfusion in ischemia-reperfusion group. It expressed most at 24 hours after ischemia-reperfusion injury. In ischemia-reperfusion and β-aescin group, IL-6 expressed at 12 hours after ischmia-reperfusion injury and reached the hightest level was lower than ischemia-reperfusion group at every stage (P 0.05). The a wave of ERG of ischemia-reperfusion group was lower than ischemia-reperfusion and β-aescin group at every stage (P 0.05). [Conclusion] IL-6 take important role in rat's retina ischemia-reperfusion injury, the β-aescni may suppress the activity of IL-6 and relieve the retina injury from the ischemia-reperfusion.
Erg
Rat model
Cite
Citations (0)
Objective:The retina ischemia-reperfusion injury is caused by many factors. A lot of cell factors take part in it. Many researches suggest MCP-1 has special effect on leukocyte and lymphocyte.The research try to study the effect of MCP-1 in rat's retina ischemia-reperfusion injury.Methods:To employ the rat's retina ischemia-reperfusion model and use SABC method to test the expression of MCP-1 on retina.Results:There was no MCP-1 expressed in retina after ischemia-reperfusion injury for one hour. MCP-1 began to express in retina after ischemia-reperfusion injury for six hours, and expressed at most after ischemia-reperfusion injury for 24 hours. Then it began to decrease in 48 hours after ischemia-reperfusion injury, but it still expressed in retina in seventy-two hours after ischemia-reperfusion injury.Conclusions:MCP-1 plays an important role in rat's retina ischemia-reperfusion injury.
Cite
Citations (0)
Objective To investigate the effect of palm oil(PO) on the volume of the infarction,the expression of Bcl-2 and Bax protein following focal cerebral ischemia/reperfusion in rats,and explore the protective effect of PO on focal cerebral ischemia/reperfusion and the underlying mechanism.Methods The acute focal cerebral ischemia/reperfusion models were established with suture emboli.Healthy male Sprague-Dawley rats were randomly divided into four groups: normal control group,sham group,IR group and PO group.There were 12 rats in each of the normal control group and the sham group.The IR group and PO group were further subdivided into subgroups and sacrificed 2 h,6 h,12 h,24 h,72 h and 7 d after ischemia/reperfusion(n=12).The volume of the infarction was observed by the TTC method;and the expression of Bcl-2 and Bax was determined by Western blotting to observe the protective effect of PO.Results ① TTC staining: there was no region of ischemia/reperfusion injury in the normal control group and the sham group.There was no region of ischemia/reperfusion injury in IR group and PO group 2 h after ischemia/reperfusion.At the time points of 6 h,12 h,24 h,72 h and 7 d after ischemia/reperfusion,there were statistical differences in mass percentage of the infracted regions between the PO group and the IR group(P0.05),and mass percentage of the infracted cerebral regions in the PO group was reduced as compared to the IR group.② Western-blotting: From the time point of 6h after reperfusion,in both PO group and IR group,the expression of Bcl-2 and Bax increased with time in the ischemia penumbra with peak expression at 12 h,and then decreased.The expression of Bax reached the peak at 24 h,and then decreased.Western-blotting analysis showed a gradual increase in Bcl-2 expression(P0.05) and a gradual decrease in Bax expression(P0.05) in PO group at each time point(6 h,12 h,24 h and 72 h after ischemia/reperfusion),compared with IR group.Conclusions ① PO can reduce the region of ischemia injury following focal cerebral ischemia/reperfusion injury;② PO can protect nerve cells by increasing the expression of Bcl-2 and decreasing the expression of Bax,following the cerebral ischemia/reperfusion injury.
Cite
Citations (0)
Carnosine
Cite
Citations (53)
Effective efforts to screen for agents that protect against the devastating effects of stroke have not produced viable results thus far. As a result this article reviews the possible role of ethanol as a neuroprotective agent in stroke and traumatic brain injury (TBI). Previous studies have associated ethanol consumption with a decreased risk of ischemic stroke, suggesting a neuroprotective mechanism. The translation of this clinical knowledge into basic science research with the goal of new therapy for acute stroke patients remains in its initial stages. In a recent study involving rats, we have shown that ethanol administration, in the correct dose after stroke onset, protects against ischemia-induced brain injury. The purpose of this paper is to discuss ethanol's neuroprotective properties in stroke when consumed as a preconditioning agent, in TBI with a positive blood alcohol content, and finally in stroke treatment, with the goal of using post-ischemia ethanol (PIE) therapy to ameliorate brain damage in the future.
Stroke
Brain ischemia
Cite
Citations (15)