scholarly journals Notoginsenoside R1 Improves Cerebral Ischemia/Reperfusion Injury by Promoting Neurogenesis via the BDNF/Akt/CREB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Zhu ◽  
Lei Wang ◽  
Weijie Xie ◽  
Xiangbao Meng ◽  
Yicheng Feng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Long Term Effects ◽  
Bdnf Expression ◽  
Neuroprotective Effects

Notoginsenoside R1 (R1), a major component isolated from P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in a rat model of ischemic stroke. However, its long-term effects on neurogenesis and neurological restoration after ischemic stroke have not been investigated. The aim of this study was to evaluate the effects of R1 on neurogenesis and long-term functional recovery after ischemic stroke. We used male Sprague-Dawley rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). R1 was administered by intraperitoneal (i.p.) injection immediately postischemia. We showed that R1 significantly decreased infarct volume and neuronal loss, restored neurological function, and stimulated neurogenesis and oligodendrogenesis in rats subjected to MCAO/R. More importantly, R1 promoted neuronal proliferation in PC12 cells in vitro. The proneurogenic effects of R1 were associated with the activation of Akt/cAMP responsive element-binding protein, as shown by the R1-induced increase in brain-derived neurotrophic factor (BDNF) expression, and with the activation of neurological function, which was partially eliminated by selective inhibitors of BDNF and PI3K. We demonstrated that R1 is a promising compound that exerts neuroprotective and proneurogenic effects, possibly via the activation of BDNF/Akt/CREB signaling. These findings offer insight into exploring new mechanisms in long-term functional recovery after R1 treatment of ischemic stroke.

scholarly journals Adiponectin Treatment Attenuates Cerebral Ischemia-Reperfusion Injury through HIF-1α-Mediated Antioxidation in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Chan Zhang ◽  
Luming Zhen ◽  
Zongping Fang ◽  
Liang Yu ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cellular Apoptosis ◽  
Cerebral Ischemia Reperfusion Injury

Adiponectin (ADPN) plays an important role in cerebral ischemia-reperfusion injury. Although previous studies have confirmed that ADPN pretreatment has a protective effect on ischemic stroke, the therapeutic effect of ADPN on ischemic stroke and the underlying mechanism are still unclear. In order to clarify these questions, focal transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in mice and ADPN was administered for three times at 6 h, 24 h, and 48 h after reperfusion. Meanwhile, a virus-delivered HIF-1α siRNA was used before ADPN administration. The infarct volume, neurological score, cellular apoptosis, and oxidative stress were assessed at 72 h after reperfusion. The long-term outcome of mice after stroke was recorded as well. The results indicated that ADPN treatment reduced the infarct volume ( P = 0.032 ), neurological deficits ( P = 0.047 ), cellular apoptosis ( P = 0.041 ), and oxidative responses ( P = 0.031 ) at 72 h after MCAO. Moreover, ADPN increased both the protein level and transcriptional activity of HIF-1α as evidenced by the transcription levels of VEGF ( P = 0.046 ) and EPO ( P = 0.043 ) at 72 h after MCAO. However, knockdown of HIF-1α partially reversed the antioxidant and treatment effect of ADPN after cerebral ischemia. In the observation of long-term outcome after ADPN treatment, it demonstrated that ADPN not only prevented the cerebral atrophy ( P = 0.031 ) and the neurological function decline ( P = 0.048 ), but also promoted angiogenesis ( P = 0.028 ) after stroke. In conclusion, our findings suggest that ADPN is effective in treatment of ischemic stroke which could be attributed to the increased antioxidant capacity regulated by HIF-1α.

Abstract TP266: Phenothiazines Enhance Mild Hypothermia-induced Neuroprotection via PI3K/Akt Regulation in Experimental Ischemia/Reperfusion Injury

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hong An ◽  
Joshua Wright ◽  
Yunxia Duan ◽  
Di Wu ◽  
Xunming Ji ◽  
...  
Keyword(s):  
Cell Death ◽  
Ischemia Reperfusion Injury ◽  
Mild Hypothermia ◽  
Apoptotic Cell ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Neuroprotective Effects ◽  
Apoptotic Proteins

Introduction: Hypothermia is an effective neuroprotectant against stroke, but its application is limited by delayed onset, prolonged duration, and significant complications. Mild hypothermia is more clinically practical but offers weaker neuroprotection. This study investigated whether the neuroprotective effects of mild hypothermia can be enhanced by phenothiazine neuroleptics (chlorpromazine and promethazine), which were reported to have depressive or hibernation-like roles on the CNS. We also worked to elucidate the role of the PI3K/Akt signaling pathway in this protective mechanism. Methods: A total of 131 adult male Sprague-Dawley rats were randomly divided into 6 groups: sham, stroke without treatment (2-hour right middle cerebral artery occlusion), and 4 treatment groups with 1) mild hypothermia (anal temperature 33-35 0 C), 2) phenothiazines (1mg/kg chlorpromazine & 1mg/kg promethazine, anal temperature 37.8-38.3 0 C), 3) combination of mild hypothermia and phenothiazines, and 4) both therapies with the addition of a p-Akt antagonist (LY294002 was injected into the lateral ventricle 30 minutes before ischemia). Infarct volume, neurological deficit, and apoptotic cell death were determined 24h post reperfusion. Expression of p-Akt, cleaved Caspase-3, pro-apoptotic (AIF & Bax) and anti-apoptotic proteins (Bcl-2 & Bcl-xL) was assessed by Western blot at 6h and 24h after reperfusion. Results: The combination of hypothermia and phenothiazines decreased (P<0.01) infarct volume and neurological deficit. This change was associated with a reduction (P<0.01) of apoptotic cell death. Each treatment alone did not induce significant neuroprotection. The combination therapy, but not each alone, promoted (P<0.01) the expression of p-Akt, accompanied with increased expression of anti-apoptotic proteins and decreased expression of pro-apoptotic proteins. The neuroprotective effects were blocked by p-Akt inhibition. Conclusion: Mild hypothermia-induced neuroprotection was enhanced by phenothiazines in an experimental ischemia/reperfusion injury model. This study supports the involvement of the PI3K/Akt signaling pathway. This novel therapeutic strategy could be developed as an effective treatment for acute ischemic stroke.

scholarly journals Cannabinoid CB1 receptor agonist ACEA alleviates brain ischemia/reperfusion injury via CB1–Drp1 pathway

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Yang ◽  
Bin Hu ◽  
Zongming Wang ◽  
Changming Zhang ◽  
Haosen Jiao ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Brain Ischemia ◽  
Receptor Agonist ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Cb1 Receptor ◽  
Cannabinoid Cb1 Receptor ◽  
Neuroprotective Effects

Abstract Activation of the cannabinoid CB1 receptor induces neuroprotection against brain ischemia/reperfusion injury (IRI); however, the mechanism is still unknown. In this study, we used oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neuronal cells and middle cerebral artery occlusion (MCAO)-induced brain IRI in rats to mimic ischemic brain injury, and hypothesized that the CB1 receptor agonist arachidonyl-2-chloroethylamide (ACEA) would protect ischemic neurons by inhibiting mitochondrial fission via dynamin-related protein 1 (Drp1). We found that OGD/R injury reduced cell viability and mitochondrial function, increased lactate dehydrogenase (LDH) release, and increased cell apoptosis, and mitochondrial fission. Notably, ACEA significantly abolished the OGD/R-induced neuronal injuries described above. Similarly, ACEA significantly reversed MCAO-induced increases in brain infarct volume, neuronal apoptosis and mitochondrial fission, leading to the recovery of neurological functions. The neuroprotective effects of ACEA were obviously blocked by coadministration of the CB1 receptor antagonist AM251 or by the upregulation of Drp1 expression, indicating that ACEA alleviates brain IRI via the CB1–Drp1 pathway. Our findings suggest that the CB1 receptor links aberrant mitochondrial fission to brain IRI, providing a new therapeutic target for brain IRI treatment.

scholarly journals Catestatin (Cst) protects the brain against ischemia/reperfusion injury through suppressing ER-stress and mitochondrial dysfunction

2020 ◽  
Author(s):  
Pei Bing ◽  
Chunjie Song ◽  
Zhengjiang Zhang ◽  
Shen Xin ◽  
Cui Qian
Keyword(s):  
Ischemic Stroke ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Function ◽  
The Brain

Abstract BackgroundCerebral stroke, known as a cerebral vascular accident (CVA), is one of the leading causes of long-term disability and the second leading cause of death worldwide. Despite amounts of advances that have been achieved in terms of the treatment of ischemic stroke. But thus far, clinically effective neuroprotectants remain elusive, which may mainly due to the lack of a complete understanding of molecular mechanisms of the stroke. Previous studies have been revealed that catestatin (Cst) is closely related to cardiovascular ischemia/reperfusion injuries. However, little is known about whether Cst is involved in the regulation of neuronal death processes during ischemia. MethodsIn the present study, we revealed a protective function of Cst on Rat neuron cell death in the setting of ischemia/reperfusion injury. ResultsWe found that Cst treatment significantly attenuated the deficits of hippocampal related behaviors. On mechanism, our data revealed that Cst administration remarkably reduced ER-stress and mitochondrial dysfunction caused by I/R injury, and subsequently protected brain cells from apoptosis. ConclusionIn sum, our results demonstrate that Cst ameliorates I/R injury-induced hippocampal-related behaviors deficits by protecting the neurons from I/R injury-induced ER-stress and mitochondrial dysfunction and apoptosis. Our findings may provide a promising novel neuroprotectant for ischemic stroke therapy.

Abstract W P97: Post-ischemic Trans-arterial Regional Hypothermia Therapy Attenuates Microvascular Narrowing due to Astrocyte End-feet Swelling and Inhibits Subsequent Inflammatory Reactions in Ischemia Reperfusion Injury

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kota Kurisu ◽  
Takeo Abumiya ◽  
Hideki Nakamura ◽  
Daisuke Shimbo ◽  
Ken Kazumata ◽  
...  
Keyword(s):  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Morphological Changes ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Saline Group ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Inflammatory Reactions ◽  
Cold Saline

Background and Purpose: We previously presented the robust neuroprotective effects of post-ischemic trans-arterial regional hypothermia therapy in I/R injury model rats (ISC 2014, San Diego). This treatment showed a significant suppression of infarct volume and inflammatory reaction at 24hrs after reperfusion. To characterize the neuroprotective effects in terms of microvascular integrity, we investigated microvascular morphological changes and inflammatory reactions by a time course analysis within 24hrs. Methods: At reperfusion onset, 2hr-MCAO rats were divided into cold saline group (10°C, 20ml/kg of trans-arterial infusion from the recanalized artery for 15mins), warm saline group (37°C, in the same manner as cold saline group), and control group (recanalization only). Microvascular morphological changes were examined by vWF Immunohistochemistry (IHC) and transmission electron microscopy (TEM), and inflammatory reactions were examined by Western blotting and IHC at the time point of 0hr, 2hrs, 6hrs, and 24hrs of reperfusion. Results: IHC analysis and TEM observation revealed that astrocyte end-feet swelling occurred at 2hrs and progressed to 6hrs, and microvascular narrowing due to the swelling occurred at 6hrs in control group. This microvascular morphological change was attenuated in cold saline group. While endothelial ICAM1 overexpression started at 6hrs in control group, MPO, MMP9, and Iba-1 overexpression occurred only at 24hrs in the same group. These inflammatory reactions were also inhibited in cold saline group. Conclusions: Post-ischemic trans-arterial regional hypothermia therapy attenuated astrocyte end-feet swelling from 2hrs and the swelling induced microvascular narrowing at 6hrs. The treatment also inhibited endothelial ICAM-1 overexpression at 6hrs, and subsequently inhibited inflammatory reactions at 24hrs. The maintenance of microvascular morphological and functional integrity may be the primary cause of the neuroprotective effects by the regional hypothermia.

scholarly journals Post-stroke treatment with argon preserved neurons and attenuated microglia/macrophage activation long-termly in a rat model of transient middle cerebral artery occlusion (tMCAO)

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingjin Liu ◽  
Michael Veldeman ◽  
Anke Höllig ◽  
Kay Nolte ◽  
Lisa Liebenstund ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Macrophage Activation ◽  
Neuroprotective Effect ◽  
Macrophage Polarization ◽  
Artery Occlusion ◽  
Brain Inflammation ◽  
Long Term Effects ◽  
Neuroprotective Effects ◽  
Stroke Treatment

AbstractIn a previous study from our group, argon has shown to significantly attenuate brain injury, reduce brain inflammation and enhance M2 microglia/macrophage polarization until 7 days after ischemic stroke. However, the long-term effects of argon have not been reported thus far. In the present study, we analyzed the underlying neuroprotective effects and potential mechanisms of argon, up to 30 days after ischemic stroke. Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion demonstrated long-term neuroprotective effect by preserving the neurons at the ischemic boundary zone 30 days after stroke. Furthermore, the excessive microglia/macrophage activation in rat brain was reduced by argon treatment 30 days after ischemic insult. However, long-lasting neurological improvement was not detectable. More sensorimotor functional measures, age- and disease-related models, as well as further histological and molecular biological analyses will be needed to extend the understanding of argon’s neuroprotective effects and mechanism of action after ischemic stroke.

scholarly journals Danggui-Shaoyao-San (DSS) Ameliorates Cerebral Ischemia-Reperfusion Injury via Activating SIRT1 Signaling and Inhibiting NADPH Oxidases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunxia Luo ◽  
Hansen Chen ◽  
Bun Tsoi ◽  
Qi Wang ◽  
Jiangang Shen
Keyword(s):  
Ischemic Stroke ◽  
Reperfusion Injury ◽  
Aqueous Extract ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Ethanol Extract ◽  
Dependent Manner ◽  
Neuroprotective Effects

Danggui-Shayao-San (DSS) is a famous Traditional Chinese Medicine formula that used for treating pain disorders and maintaining neurological health. Recent studies indicate that DSS has neuroprotective effects against ischemic brain damage but its underlining mechanisms remain unclear. Herein, we investigated the neuroprotective mechanisms of DSS for treating ischemic stroke. Adult male Sprague-Dawley (S.D.) rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 22 h of reperfusion. Both ethanol extract and aqueous extract of DSS (12 g/kg) were orally administrated into the rats at 30 min prior to MCAO ischemic onset. We found that 1) ethanol extract of DSS, instead of aqueous extract, reduced infarct sizes and improved neurological deficit scores in the post-ischemic stroke rats; 2) Ethanol extract of DSS down-regulated the expression of the cleaved-caspase 3 and Bax, up-regulated bcl-2 and attenuated apoptotic cell death in the ischemic brains; 3) Ethanol extract of DSS decreased the production of superoxide and peroxynitrite; 4) Ethanol extract of DSS significantly down-regulated the expression of p67phox but has no effect on p47phox and iNOS statistically. 5) Ethanol extract of DSS significantly up-regulated the expression of SIRT1 in the cortex and striatum of the post-ischemic brains; 6) Co-treatment of EX527, a SIRT1 inhibitor, abolished the DSS’s neuroprotective effects. Taken together, DSS could attenuate oxidative/nitrosative stress and inhibit neuronal apoptosis against cerebral ischemic-reperfusion injury via SIRT1-dependent manner.

Protective Effect of Capparis spinosa Extract Against Focal Cerebral Ischemia-Reperfusion Injury in Rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Hassan Rakhshandeh ◽  
Samira Asgharzade ◽  
Mohammad Bagher Khorrami ◽  
Fatemeh Forouzanfar
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Public Health Problem ◽  
Artery Occlusion ◽  
Stroke Group ◽  
Capparis Spinosa

Background: Ischemic stroke is a serious public health problem. Despite extensive research focusing on the area, little is known about novel treatments. Objective: In this study, we aimed to investigate the effects of Capparis spinosa (C. spinosa) extract in the middle cerebral artery occlusion (MCAO) model of ischemic stroke. Methods: Wistar rats underwent 30-min MCAO-induced brain ischemia followed by 24 h of reperfusion. C. spinose was administrated orally once a day for 7 days before the induction of MCAO. The neurologic outcome, infarct volume (TTC staining), histological examination, and markers of oxidative stress, including total thiol content and malondialdehyde (MDA) levels, were measured 24 hr. after the termination of MCAO. Results: Pretreatment with C. spinosa, reduced neurological deficit score, histopathological alterations, and infarct volume in treated groups compared to stroke group. Furthermore, pretreatment with C. spinosa extract significantly reduced the level of MDA with concomitant increases in the levels of thiol in the brain tissues compared with the stroke group. Conclusion: Our study demonstrates that C. spinosa extract effectively protects MCAO injury through attenuation of suppressing oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document