scholarly journals Gap Junctional Coupling Between Retinal Astrocytes Exacerbates Neuronal Damage in Ischemia-Reperfusion Injury

2021 ◽  
Vol 62 (14) ◽  
pp. 27
Author(s):  
Abduqodir H. Toychiev ◽  
Khulan Batsuuri ◽  
Miduturu Srinivas
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Retinal Astrocytes ◽  
Junctional Coupling ◽  
Gap Junctional ◽  
Gap Junctional Coupling

scholarly journals N6-methyladenosine demethylases Alkbh5/Fto regulate cerebral ischemia-reperfusion injury

2020 ◽  
Vol 11 ◽  
pp. 204062232091602 ◽  
Author(s):  
Kaiwei Xu ◽  
Yunchang Mo ◽  
Dan Li ◽  
Qimin Yu ◽  
Lu Wang ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Background: Although N6-methyladenosine (m6A) plays a very important role in different biological processes, its function in the brain has not been fully explored. Thus, we investigated the roles of the RNA demethylases Alkbh5/Fto in cerebral ischemia-reperfusion injury. Methods: We used a rat model and primary neuronal cell culture to study the role of m6A and Alkbh5/Fto in the cerebral cortex ischemic penumbra after cerebral ischemia-reperfusion injury. We used Alkbh5-shRNA and Lv-Fto ( in vitro) to regulate the expression of Alkbh5/Fto to study their regulation of m6A in the cerebral cortex and to study brain function after ischemia-reperfusion injury. Results: We found that RNA m6A levels increased consecutive to the increase of Alkbh5 expression in both the cerebral cortex of rats after middle cerebral artery occlusion, and in primary neurons after oxygen deprivation/reoxygenation. In contrast, Fto expression decreased after these perturbations. Our results suggest that knocking down Alkbh5 can aggravate neuronal damage. This is due to the demethylation of Alkbh5 and Fto, which selectively demethylate the Bcl2 transcript, preventing Bcl2 transcript degradation and enhancing Bcl2 protein expression. Conclusion: Collectively, our results demonstrate that the demethylases Alkbh5/Fto co-regulate m6A demethylation, which plays a crucial role in cerebral ischemia-reperfusion injury. The results provide novel insights into potential therapeutic mechanisms for stroke.

Neuroprotective Effect of Urinary Trypsin Inhibitor against Focal Cerebral Ischemia–Reperfusion Injury in Rats

2003 ◽  
Vol 98 (2) ◽  
pp. 465-473 ◽  
Author(s):  
Toshiyuki Yano ◽  
Sakiko Anraku ◽  
Ryosuke Nakayama ◽  
Kazuo Ushijima
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Trypsin Inhibitor ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Saline Control ◽  
Urinary Trypsin Inhibitor ◽  
Cerebral Ischemia Reperfusion

Background Acute inflammatory reactions cause neuronal damage in cerebral ischemia-reperfusion. Urinary trypsin inhibitor (UTI), a serine protease inhibitor, is cytoprotective against ischemia-reperfusion injury in the liver, intestine, kidney, heart, and lung through its antiinflammatory activity. Neuroprotective action of UTI on transient global cerebral ischemia has been documented. This is the first study to determine whether UTI is neuroprotective against transient focal cerebral ischemia. Methods Adult male Wistar rats were randomly assigned to the following treatment groups: 0.9% saline (control, n = 9); 100,000 U/kg UTI (n = 9); and 300,000 U/kg UTI (n = 9). Treatments were performed intravenously 10 min before right middle cerebral artery occlusion for 2 h and subsequent reperfusion. Ninety-six hours after the onset of reperfusion, the motor neurologic deficit and the cerebral infarct size were evaluated. Furthermore, immunohistochemical staining for myeloperoxidase and nitrotyrosine to count infiltrating neutrophils and nitrated cells, respectively, was performed on the brain sections. Results Infarct volume in the 300,000 U/kg UTI group was smaller than in the 100,000 U/kg UTI and saline control groups (P < 0.05). Treatment with 300,000 U/kg UTI showed a trend to improve neurologic outcome but did not reach statistical significance (P = 0.0693). The significant decrease in neutrophil infiltration was observed in the ischemic hemisphere treated with 300,000 U/kg UTI compared with saline control (P < 0.05). Nitrotyrosine deposition in the ischemic hemisphere was significantly reduced in the 300,000 U/kg UTI group compared with saline control and 100,000 U/kg UTI groups (P < 0.05). Conclusions Intravenous pretreatment with 300,000 U/kg UTI reduces focal ischemia-reperfusion injury in the rat brain, potentially opening a novel therapeutic avenue for the treatment of cerebral ischemia.

Argon reduces microglia activation and ramification dependent inflammatory cytokine expression in the retina

2019 ◽  
Author(s):  
Ulrich Goebel ◽  
Stefanie Scheid ◽  
Sashko Spassov ◽  
Nils Schallner ◽  
Jakob Wollborn ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Noble Gas ◽  
Ischemia Reperfusion ◽  
Microglia Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Human Neuroblastoma

Abstract Background: Perioperative damage of neuronal tissue due to insufficient cerebral circulation as a result of hypotension or stroke, lead to permanent destruction and functional impairment via apoptotic and inflammatory pathways. Recently, the noble gas argon has been shown to exert neuroprotective effects. Despite intensive research, the exact mechanism remains unclear. Methods: In-vitro, after injury of human neuroblastoma cells with rotenone over a period of four hours, postconditioning with argon 75 Vol% was performed for 2. In-vivo, retinal ischemia reperfusion injury in the rat was induced by increasing intraocular pressure for 1 hour (h). Upon reperfusion, argon was administered by inhalation for 2 h. Results: In summary, argon reduced binding activity of transcription factors involved in regulation of neuronal damage such as STAT3 (Signal transducer and activator of transcription 3), NF-kB (Nuclear factor `kappa-light-chain-enhancer´ of activated B-cells), AP-1 (Activator protein 1) and Nrf-2 (Nuclear factor erythroid 2-related factor 2). Flow cytometry analysis showed that argon down-regulated the Fas-Ligand. Since some of these transcription factors were regulated via toll-like receptors (TLR), their effects could be eliminated - at least in part - by OxPAPC (TLR2 and -4 inhibitor). Argon was able to reduce the quantity and the activity of neuronal microglia after ischemia-reperfusion injury. Consecutively, qPCR (quantitative Polymerase chain reaction) showed a reduction of the pro-inflammatory cytokines IL-1α (Interleukin-1α), IL-1ß (Interleukin-1ß), IL-6 (Interleukin 6), TNFα (Tumor necrosis factor alpha) and iNOS (inducible Nitric oxide synthase). Conclusion: Argon reduced the extent of inflammation after neuronal injury by suppression of transcription factors crucial for microglia activation. The therapeutic use of the noble gas would be ideal for treating in the context of neuronal damage due to the lack of known side effects and narcotic properties with preservation of neurological assessability. Although preclinical studies are promising, further investigations are required before argon can be approved for use in patients.

scholarly journals Inhibition of autophagy by CRMP2-derived peptide ST2-104 (R9-CBD3) via a CaMKKβ/AMPK/mTOR pathway contributes to ischemic postconditioning-induced neuroprotection against cerebral ischemia-reperfusion injury

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuan Yao ◽  
Yingshi Ji ◽  
Jinghong Ren ◽  
Huanyu Liu ◽  
Rajesh Khanna ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Mtor Pathway ◽  
Cerebral Ischemia Reperfusion ◽  
Model Of Alzheimer’S Disease ◽  
Cerebral Ischemia Reperfusion Injury

AbstractCerebral ischemia, a common cerebrovascular disease, is characterized by functional deficits and apoptotic cell death. Autophagy, a type of programmed cell death, plays critical roles in controlling neuronal damage and metabolic homeostasis, and has been inextricably linked to cerebral ischemia. We previously identified a short peptide aptamer from collapsin response mediator protein 2 (CRMP2), designated the Ca2+ channel-binding domain 3 (CBD3) peptide, that conferred protection against excitotoxicity and traumatic brain injury. ST2-104, a nona-arginine (R9)-fused CBD3 peptide, exerted beneficial effects on neuropathic pain and was neuroprotective in a model of Alzheimer’s disease; however, the effect of ST2-104 on cerebral ischemia and its mechanism of action have not been studied. In this study, we modeled cerebral ischemia–reperfusion injury in rats with the middle cerebral artery occlusion (MCAO) as well as challenged SH-SY5Y neuroblastoma cells with glutamate to induce toxicity to interrogate the effects of ST2-104 on autophagy following ischemic/excitotoxic insults. ST2-104 reduced the infarct volume and improved the neurological score of rats subjected to MCAO. ST2-104 protected SH-SY5Y cells from death following glutamate exposure via blunting apoptosis and autophagy as well as limiting excessive calcium entry. 3-Methyladenine (3-MA), an inhibitor of autophagy, promoted the effects of ST2-104 in inhibiting apoptosis triggered by glutamate while rapamycin, an activator of autophagy, failed to do so. ST2-104 peptide reversed glutamate-induced apoptosis via inhibiting Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-mediated autophagy, which was partly enhanced by STO-609 (an inhibitor of CaMKKβ). ST2-104 attenuated neuronal apoptosis by inhibiting autophagy through CaMKKβ/AMPK/mTOR pathway. Our results suggest that the neuroprotective effect of ST2-104 are due to actions on the crosstalk between apoptosis and autophagy via the CaMKKβ/AMPK/mTOR signaling pathway. The findings present novel insights into the potential neuroprotection of ST2-104 in cerebral ischemia.

scholarly journals Populus tomentiglandulosa Extract Is Rich in Polyphenols and Protects Neurons, Astrocytes, and the Blood-Brain Barrier in Gerbil Striatum Following Ischemia-Reperfusion Injury

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5430
Author(s):  
Tae-Kyeong Lee ◽  
Jae-Chul Lee ◽  
Jong-Dai Kim ◽  
Dae-Won Kim ◽  
Ji-Hyeon Ahn ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Reperfusion Injury ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Brain Barrier ◽  
Transient Ischemia ◽  
Blood Brain ◽  
Pre Treatment

Transient ischemia in brains causes neuronal damage, gliosis, and blood–brain barrier (BBB) breakdown, which is related to ischemia-induced brain dysfunction. Populus species have various pharmacological properties including antioxidant and anti-inflammatory activities. In this study, we found that phenolic compounds were rich in Populus tomentiglandulosa extract and examined the effects of Populus tomentiglandulosa extract on neuronal damage/death, astrogliosis, and BBB breakdown in the striatum, which is related to motor behavior, following 15-min transient ischemia in the forebrain in gerbils. The gerbils were pre-treated with 50, 100, and 200 mg/kg of the extract. The latter showed significant effects against ischemia-reperfusion injury. Ischemia-induced hyperactivity using spontaneous motor activity test was significantly attenuated by the treatment. Striatal cells (neurons) were dead at five days after the ischemia; however, pre-treatment with the extract protected the striatal cells from ischemia/reperfusion injury. Ischemia-induced reactive astrogliosis was significantly alleviated, in particular, astrocyte end feet, which are a component of BBB, were significantly preserved. Immunoglobulin G, which is not found in intact brain parenchyma, was apparently shown (an indicator of extravasation) in striatal parenchyma at five days after the ischemia, but IgG leakage was dramatically attenuated in the parenchyma by the pre-treatment. Based on these findings, we suggest that Populus tomentiglandulosa extract rich in phenolic compounds can be employed as a pharmaceutical composition to develop a preventive material against brain ischemic injury.

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