scholarly journals Ilexonin A Promotes Neuronal Proliferation and Regeneration via Activation of the Canonical Wnt Signaling Pathway after Cerebral Ischemia Reperfusion in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Bi-Qin Zhang ◽  
Guan-Yi Zheng ◽  
Yu Han ◽  
Xiao-Dong Chen ◽  
Qiong Jiang
Keyword(s):  
Cerebral Ischemia ◽  
Wnt Pathway ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Wnt Signaling Pathway ◽  
Neurological Deficits ◽  
Canonical Wnt Pathway ◽  
Cerebral Ischemia Reperfusion ◽  
Neuronal Proliferation ◽  
Canonical Wnt

Aims. Ilexonin A (IA), a component of the Chinese medicineIlex pubescens, has been shown to be neuroprotective during ischemic injury. However, the specific mechanism underlying this neuroprotective effect remains unclear.Methods. In this study, we employed a combination of immunofluorescence staining, western blotting, RT-PCR, and behavioral tests, to investigate the molecular mechanisms involved in IA regulation of neuronal proliferation and regeneration after cerebral ischemia and reperfusion in rodents.Results. Increases inβ-catenin protein and LEF1 mRNA and decreases in GSK3βprotein and Axin mRNA observed in IA-treated compared to control rodents implicated the canonical Wnt pathway as a key signaling mechanism activated by IA treatment. Furthermore, rodents in the IA treatment group showed less neurologic impairment and a corresponding increase in the number of Brdu/nestin and Brdu/NeuN double positive neurons in the parenchymal ischemia tissue following middle cerebral artery occlusion compared to matched controls.Conclusion. Altogether, our data indicate that IA can significantly diminish neurological deficits associated with cerebral ischemia reperfusion in rats as a result of increased neuronal survival via modulation of the canonical Wnt pathway.

scholarly journals Tetrandrine alleviates cerebral ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via Sirt-1

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9042
Author(s):  
Jun Wang ◽  
Ming Guo ◽  
Ruojia Ma ◽  
Maolin Wu ◽  
Yamei Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Sirtuin 1 ◽  
Neurological Deficits ◽  
Inflammasome Activation ◽  
Cerebral Ischemia Reperfusion ◽  
Nlrp3 Inflammasome Activation

Background & Aims Tetrandrine (Tet) has been reported to have anti-inflammatory effects and protect from the ischemic strokes. The NLRP3 inflammasome plays a key role in cerebral ischemia/reperfusion (I/R)-induced inflammatory lesions. However, the molecular mechanisms of Tet related to the progression of cerebral ischemia are still unclear. Therefore, the aim of this study was to investigate the possible effects of Tet on cerebral ischemia and the related mechanisms involved in NLRP3 inflammasome. Methods C57BL/6J mice used as a cerebral I/R injury model underwent middle cerebral artery occlusion (MCAO) for 2 h following reperfusion for 24 h. Tet (30 mg/kg/day, i.p.) was administered for seven days and 30 min before and after MCAO. Their brain tissues were evaluated for NLRP3 inflammasome and Sirtuin-1 (Sirt-1) expression. An intracerebroventricular injection of Sirt-1 siRNA was administered to assess the activation of the NLRP3 inflammasome. Results Tet significantly reduced the neurological deficits, infarction volume, and cerebral water content in MCAO mice. Moreover, it inhibited I/R-induced over expression of NLRP3, cleaved caspase-1, interleukin (IL)-1β, IL-18, and Sirt-1. Sirt-1 knockdown with siRNA greatly blocked the Tet-induced reduction of neurological severity score and infarct volume, and reversed the inhibition of NLRP3 inflammasome activation. Conclusion Our results demonstrate that Tet has benefits for cerebral I/R injury, which are partially related to the suppression of NLRP3 inflammasome activation via upregulating Sirt-1.

Nomilin protects against cerebral ischemia–reperfusion induced neurological deficits and blood–brain barrier disruption via the Nrf2 pathway

2019 ◽  
Vol 10 (9) ◽  
pp. 5323-5332 ◽  
Author(s):  
Yu-Sheng Shi ◽  
Yan Zhang ◽  
Bin Liu ◽  
Chun-Bin Li ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Nrf2 Pathway ◽  
Blood Brain Barrier Disruption ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Brain Barrier Disruption

Oxidative stress is considered to play an important role in the cerebral ischemia–reperfusion injury.

scholarly journals Destructive Effects of Pyroptosis on Homeostasis of Neuron Survival Associated with the Dysfunctional BBB-Glymphatic System and Amyloid-Beta Accumulation after Cerebral Ischemia/Reperfusion in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zhongkuan Lyu ◽  
Yuanjin Chan ◽  
Qiyue Li ◽  
Qiang Zhang ◽  
Kaili Liu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Amyloid Beta ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Specific Marker ◽  
Nissl Staining ◽  
Glymphatic System ◽  
Cerebral Ischemia Reperfusion

Neuroinflammation-related amyloid-beta peptide (Aβ) accumulation after cerebral ischemia/reperfusion (I/R) accounts for cerebral I/R injuries and poststroke dementia. Recently, pyroptosis, a proinflammatory cell death, has been identified as a crucial pathological link of cerebral I/R injuries. However, whether pyroptosis acts as a trigger of Aβ accumulation after cerebral I/R has not yet been demonstrated. Blood-brain barrier (BBB) and glymphatic system mediated by aquaporin-4 (AQP-4) on astrocytic endfeet are important pathways for the clearance of Aβ in the brain, and pyroptosis especially occurring in astrocytes after cerebral I/R potentially damages BBB integrity and glymphatic function and thus influences Aβ clearance and brain homeostasis. In present study, the method of middle cerebral artery occlusion/reperfusion (MCAO/R) was used for building models of focal cerebral I/R injuries in rats. Then, we used lipopolysaccharide and glycine as the agonist and inhibitor of pyroptosis, respectively, Western blotting for detections of pyroptosis, AQP-4, and Aβ1-42 oligomers, laser confocal microscopy for observations of pyroptosis and Aβ locations, and immunohistochemical stainings of SMI 71 (a specific marker for BBB integrity)/AQP-4 and Nissl staining for evaluating, respectively, BBB-glymphatic system and neuronal damage. The results showed that pyroptosis obviously promoted the loss of BBB integrity and AQP-4 polarization, brain edema, Aβ accumulation, and the formation of Aβ1-42 oligomers and thus increased neuronal damage after cerebral I/R. However, glycine could inhibit cerebral I/R-induced pyroptosis by alleviating cytomembrane damage and downregulating expression levels of cleaved caspase-11/1, N-terminal gasdermin D, NLRP3 (nucleotide-binding domain, leucine-rich repeat containing protein 3), interleukin-6 (IL-6) and IL-1β and markedly abate above pathological changes. Our study revealed that pyroptosis is a considerable factor causing toxic Aβ accumulation, dysfunctional BBB-glymphatic system, and neurological deficits after cerebral I/R, suggesting that targeting pyroptosis is a potential strategy for the prevention of ischemic stroke sequelae including dementia.

Abstract 137: The Effect Of Mitophagy During Transient Ischemic Brain In Rats

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Qiang Li ◽  
Ting Zhang ◽  
Jixian Wang ◽  
Yongting Wang ◽  
Guo-Yuan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Atp Synthesis ◽  
Beclin 1 ◽  
Neurological Deficits ◽  
Ischemic Brain ◽  
Pre Treatment ◽  
The Impact

Background and Purpose: Mitochondria provides energy to maintain normal cell functioning. Mitophagy is one of mitochondria functions, which can clear out injured mitochondria, ensure stability of mitochondria and promote cell survival in hostile environment. However, if mitophagy occurs during cerebral ischemia is unknown. The present study explored dynamic mitophagy, the effect of promoting mitophagy, and the molecular mechanisms of mitophagy during cerebral ischemia/reperfusion. Methods: Adult male SD rats underwent 2h middle cerebral artery occlusion (MCAO) followed by 6 to 72h reperfusion. Dynamic changes of mitophagy were determined by LC3 immunostaining, Western blot analysis, and transmission electron microscope. To study the impact of mitophagy, we injected rapamycin, a mitophagy stimulator, into the left ventricle in rats underwent transient MCAO. To evaluate the effect of mitophagy, neuronal death and neurological deficits were determined. To explore the effect of mitophagy on mitochondria function, the number of mitochondria, the levels of MDA, ATP, and JC-1 were examined. To study the mechanism of mitophagy, mitochondrial Beclin-1 and p62 expression were also determined. Results: We demonstrated that autophagy was mainly detected in mitochondria in the peri-focal area of ischemic cortex after ischemia/reperfusion. Mitophagy was increased at 6h (p<0.05), peaked at 24h (p<0.05), gradually reduced at 48h (p<0.05), and returned to normal at 72h of transient MCAO. Pre-treatment with rapamycin greatly enhanced mitophagy, reduced infarct volume, and improved neurological outcomes compared to the control (p<0.05). We found that the number of mitochondria and mtDNA copy, mitochondria ATP synthesis level, and JC-1 were increased (p<0.05), and MDA was reduced in rapamycin treated rats (p<0.05). We further demonstrated that rapamycin pre-treatment enhanced mitochondrial Beclin-1and p62 in mitochondria. Conclusion: We demonstrated ischemia could induce mitophagy in brain cells. Rapamycin attenuated ischemic brain injury, which was via stimulating mitophagy that can reduce oxidative stress and improve mitochondria function. The mechanism of rapamycin promoting mitophagy was through increasing Beclin-1 and p62 expression.

scholarly journals Neuroprotective Effect Of Musk On Rat Brain Ischemic Model

2020 ◽  
Author(s):  
Radnaa Gochoo ◽  
Oyuntsetseg Namsrai ◽  
Dagvatseren Begzsuren ◽  
Bat-Erdene Jargalsaikhan ◽  
Chimedragchaa Chimedtseren
Keyword(s):  
Cerebral Ischemia ◽  
Rat Brain ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Neurological Deficits ◽  
Control Group ◽  
Ischemic Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Significant Difference

Abstract Background Stroke is leading cause of morbidity and mortality in worldwide. Despite valuable progresses in understanding neurological deficits after stroke, its therapeutic options are remaining limited. We aimed to study the neuroprotective effect of musk on cerebral ischemia/reperfusion injury model rats.Methods:In our experiment, we used 180 whore meal breed Wistar rats which weigh 180-220 g and divided these rats into 50 mg/kg of musk, 100 mg/kg of musk, 10 mg/kg of nimodipine, the ischemic-reperfusion groups by filling the midriff of the brain and take the drugs for 7 days in each group. Cerebral ischemia/reperfusion was induced in rats by temporary middle cerebral artery occlusion-reperfusion (MCAO/R) followed by treatment with musk at 50 mg/kg and 100 mg/kg doses. On days 1, 3 and 7 after MCAO/R, TGF-β, BDNF, TrkB and NGF mRNA expressions in the rat brain tissue were quantitatively analyzed using RT-PCR.Results:Musk 50 and 100 mg/kg treated groups brain stroke size were significantly decreased compared with the experimental group at 1, 3 and 7 days. Moreover, brain BDNF, TrkB, NGF and TGF-β mRNA express were not significant difference between experimental and control group. Also 3rd and 7th day, the data indicate that Musk 50 and 100 mg/kg were significantly (p<0,05) effective increasing rats brain BDNF, TrkB, NGF and TGF- β mRNA express in rats with ischemic stroke induced by MCAO/R. Conclusions: The 50 and 100 mg/kg doses of musk lead to increase neuro-protective factors BDNF, TRkB, NGF and TGF- β expression of mRNA in ischemic-reperfusion rat model. It implies that the Mongolian musk supports the neurogenesis of neuronal cell.

scholarly journals Canonical Wnt Signaling Pathway on Polarity Formation of Utricle Hair Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Di Deng ◽  
Xiaoqing Qian ◽  
Binjun Chen ◽  
Xiaoyu Yang ◽  
Yanmei Wang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Inner Ear ◽  
Signaling Pathway ◽  
Hair Cells ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Canonical Wnt Signaling ◽  
Stage Of Development ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

As part of the inner ear, the vestibular system is responsible for sense of balance, which consists of three semicircular canals, the utricle, and the saccule. Increasing evidence has indicated that the noncanonical Wnt/PCP signaling pathway plays a significant role in the development of the polarity of the inner ear. However, the role of canonical Wnt signaling in the polarity of the vestibule is still not completely clear. In this study, we found that canonical Wnt pathway-related genes are expressed in the early stage of development of the utricle and change dynamically. We conditionally knocked out β-catenin, a canonical Wnt signaling core protein, and found that the cilia orientation of hair cells was disordered with reduced number of hair cells in the utricle. Moreover, regulating the canonical Wnt pathway (Licl and IWP2) in vitro also affected hair cell polarity and indicated that Axin2 may be important in this process. In conclusion, our results not only confirm that the regulation of canonical Wnt signaling affects the number of hair cells in the utricle but also provide evidence for its role in polarity development.

scholarly journals Inhibition of miR-34a ameliorates cerebral ischemia/reperfusion injury by targeting brain-derived neurotrophic factor

2021 ◽  
Author(s):  
Shilin Zhu ◽  
Jianghong Tang ◽  
Lan Lan ◽  
Feng Su
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Neurotrophic Factor ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

IntroductionOxidative stress and neuronal apoptosis are strongly associated with the pathogenesis of ischemic stroke. In this study, we aimed to determine whether miR-34a was involved in ischemia/reperfusion (I/R) injury, oxidative stress, and neuronal apoptosis by targeting brain-derived neurotrophic factor (BDNF).Material and methodsRats received middle cerebral artery occlusion (MCAO) surgery to simulate I/R injury. At 24 h after MCAO surgery, neurological deficits and infarct volumes were evaluated according to Longa’s scale and 2,3,5-triphenyltetrazolium (TTC) chloride staining. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and the expression of miR-34a and associated proteins were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting. Several markers of oxidative stress were detected using commercial kits, and the interaction between miR-34a and BDNF was measured by RNA immunoprecipitation (RIP).ResultsThe results showed that miR-34a was upregulated (p < 0.05), whereas BDNF was downregulated (p < 0.05) in the MCAO rats, and this negative correlation was accompanied by clear oxidative stress and neuronal apoptosis. RIP demonstrated a clear interaction between miR-34a and BDNF. Furthermore, miR-34a was also found to inhibit oxidative stress and neuronal apoptosis, increase BDNF expression, and ameliorate neurological deficits and infarct volumes (p < 0.05) seen in the MCAO rats.ConclusionsThese data suggested that inhibition of miR-34a ameliorated cerebral ischemia/reperfusion injury by targeting BDNF. This mechanism represents a novel and promising target for the treatment of strokes.

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