scholarly journals HIF inhibitor topotecan has a neuroprotective effect in a murine retinal ischemia-reperfusion model

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7849 ◽  
Author(s):  
Hiromitsu Kunimi ◽  
Yukihiro Miwa ◽  
Yusaku Katada ◽  
Kazuo Tsubota ◽  
Toshihide Kurihara
Keyword(s):  
Intraocular Pressure ◽  
Visual Evoked Potentials ◽  
Retinal Thickness ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Retinal Ischemia ◽  
Retinal Ganglion ◽  
Neuroprotective Effects ◽  
Retinal Neurodegeneration

Purpose The therapeutic approach for retinal ganglion cell (RGC) degeneration has not been fully established. Recently, it has been reported that hypoxia-inducible factor (HIF) may be involved with retinal neurodegeneration. In this study, we investigated neuroprotective effects of a HIF inhibitor against RGC degeneration induced in a murine model of retinal ischemia-reperfusion (I/R). Methods Eight-weeks-old male C57/BL6J mice were treated with intraperitoneal injection of a HIF inhibitor topotecan (1.25 mg/kg) for 14 days followed by a retinal I/R procedure. Seven days after the I/R injury, the therapeutic effect was evaluated histologically and electrophysiologically. Results The increase of HIF-1α expression and the decrease of retinal thickness and RGC number in I/R were significantly suppressed by administration of topotecan. Impaired visual function in I/R was improved by topotecan evaluated with electroretinogram and visual evoked potentials. Conclusions Topotecan administration suppressed HIF-1a expression and improved RGC survival resulting in a functional protection against retinal I/R. These data indicated that the HIF inhibitor topotecan may have therapeutic potentials for RGC degeneration induced with retinal ischemia or high intraocular pressure.

scholarly journals A Novel HIF Inhibitor Halofuginone Prevents Neurodegeneration in a Murine Model of Retinal Ischemia-Reperfusion

2019 ◽  
Vol 20 (13) ◽  
pp. 3171 ◽  
Author(s):  
Hiromitsu Kunimi ◽  
Yukihiro Miwa ◽  
Hiroyoshi Inoue ◽  
Kazuo Tsubota ◽  
Toshihide Kurihara
Keyword(s):  
Intraocular Pressure ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Retinal Ischemia ◽  
In Vitro Screening ◽  
Degenerative Diseases ◽  
Retinal Degenerative Diseases

Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.

scholarly journals Sulforaphane alleviates retinal ganglion cell death and inflammation by suppressing NLRP3 inflammasome activation in a rat model of retinal ischemia/reperfusion injury

2019 ◽  
Vol 33 ◽  
pp. 205873841986177 ◽  
Author(s):  
Yuerong Gong ◽  
Xiaoning Cao ◽  
Lei Gong ◽  
Weiguo Li
Keyword(s):  
Ganglion Cell ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Retinal Thickness ◽  
Ischemia Reperfusion ◽  
Retinal Ischemia ◽  
Inflammasome Activation ◽  
Retinal Ganglion ◽  
Thickness Change ◽  
Nlrp3 Inflammasome Activation

This study aims to study the potentials of sulforaphane (SFN) against retinal ischemia/reperfusion (I/R) injury. A rat retinal I/R injury method was established. Retinal thickness change and retinal ganglion cell (RGC) death were determined using hematoxylin and eosin (H&E) staining and Fluoro-Gold (FG) labeling. The inflammatory cytokines production and microglia activation were evaluated by using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and enzyme-linked immunosorbent assay (ELISA). Knockdown NLRP3 was performed, and the according changes of retinal RGCs were assessed. SFN administration significantly inhibited I/R and caused retinal thickness change and prevented RGCs death in retinal I/R model. SFN suppressed inflammatory cytokines production, microglia activation, and inflammasome activation. In accordance, NLRP3 knockdown presented the similar inhibitory effect on I/R rats. This study demonstrates that SFN prevents RGCs death and acts as a potent neuroprotective modulator in retinal I/R injury, which may be associated with inhibition of the NLRP3 inflammasome activation.

scholarly journals Neuroprotective Effect of Orexin-A Is Mediated by an Increase of Hypoxia-inducible Factor-1 Activity in Rat

2011 ◽  
Vol 114 (2) ◽  
pp. 340-354 ◽  
Author(s):  
Li-bang Yuan ◽  
Hai-long Dong ◽  
Hao-Peng Zhang ◽  
Rui-ni Zhao ◽  
Gu Gong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Orexin A ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Background Recent studies suggest that the novel neuropeptide orexin-A may play an essential role during neuronal damage. However, the function of orexin-A during brain ischemia remains unclear. Recently, hypoxia-inducible factor-1α (HIF-1α) was shown to be activated by orexin-A. The aim of the current study is to test the hypothesis that administration of exogenous orexin-A can attenuate ischemia-reperfusion injury through the facilitation of HIF-1α expression. Methods Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion for 120 min. Rats were treated with different doses of orexin-A or vehicle before the ischemia and at the onset of reperfusion. To investigate the action of HIF-1α in the neuroprotective effects of orexin-A, the HIF-1α inhibitor YC-1 was used alone or combined with orexin-A. Neurologic deficit scores and infarct volume were assessed. Brains were harvested for immunohistochemical staining and western blot analysis. Results Orexin-A significantly ameliorated neurologic deficit scores and reduced infarct volume after cerebral ischemia reperfusion. Administration of 30 μg/kg orexin-A showed optimal neuroprotective effects. This effect was still present 7 days after reperfusion. Furthermore, orexin-A decreased the number of apoptotic cells and significantly enhanced HIF-1α expression after cerebral ischemia reperfusion. Moreover, the facilitation of HIF-1α expression was accompanied with inhibition of von Hippel-Lindau expression. Administration of HIF-1α inhibitor suppressed the increase of HIF-1α and reversed the neuroprotective effects of orexin-A. Conclusions Orexin-A has a neuroprotective effect against cerebral ischemia-reperfusion injury. These effects may be mediated through the HIF-1α pathway.

THE NEUROPROTECTIVE EFFECTS ON RETINAL STRUCTURE BY MINOCYCLINE IN A RAT MODEL OF HIGH IOP INDUCED RETINAL ISCHEMIA INJURY

2014 ◽  
Vol 40 (02) ◽  
pp. 83-87
Author(s):  
Pei-Yun Huang ◽  
Chung-Tien Lin
Keyword(s):  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Outer Nuclear Layer ◽  
Plexiform Layer ◽  
Retinal Ischemia ◽  
Control Group ◽  
Inner Plexiform Layer ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Retinal Structure

The present study investigated the neuroprotective effect of minocycline, a microglial inhibitor, against the retinal ischemia–reperfusion (IR) injury in the rat. The retinal IR injury was induced in Sprague–Dawley (SD) rats by infusing normal saline into anterior chamber of eye to create a higher intraocular pressure (IOP) than blood pressure for 45 min. Minocycline (45 and 90 mg/kg/day) was administered intraperitoneally to rats receiving IR injury. The neuroprotective effects were evaluated by morphometrical histology analysis 7 days after ischemia. The data was compared with the groups treated with saline and methylprenisolone (MP, 30 mg/kg, IV). The results showed that the retinal inner plexiform layer/outer nuclear layer (IPL/ONL) ratio was reduced following IR damage compared with that in the normal control. The IPL/ONL ratio was reduced to 43.5% in the IR-control group, 93.3% and 93.6% in the Mino-45 and Mino-90 group. The IPL/ONL ratio was preserved to 95.7% in the MP group. These results suggest that minocycline and methylprednisolone showed significantly good neuroprotective effects demonstrated in retinal histology of the rats under retinal IR injury.

Neuroprotective Effects of Alisol A 24-acetate on Cerebral Ischemia-reperfusion Injury by Regulating PI3K/AKT Pathway

2021 ◽  
Author(s):  
Taotao Lu ◽  
Huihong Li ◽  
Yangjie Zhou ◽  
Wei Wei ◽  
Linlin Ding ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Brain Regions ◽  
Global Cerebral Ischemia ◽  
Akt Pathway ◽  
Object Recognition Test ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Abstract BackgroundNeuroinflammation and apoptosis are involved in the pathogenesis of ischemic stroke. Alisol A 24-acetate (24A) has a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A in the global cerebral ischemia/ reperfusion (GCI/R) is still unclear. Methods GCI/R mice was used to investigated the neuroprotective effect of 24A. Modified neurological deficit scores, Morris Water Maze and object recognition test were used to evaluate behaviors. The metabolism in brain regions was detected by MRS. The changes of microglia, astrocytes and neurons was detected. The inflammation and apoptosis were measured.Results The results showed that 24A improved behavioral dysfunction and brain metabolism, alleviate neuroinflammation and apoptosis, inhibited microglia and astrocytes activation, which is associated with the activation of PI3K/AKT pathway. ConclusionsTaken together, our study demonstrated that 24A could alleviate GCI/R injury through anti-neuroinflammation and anti-apoptosis via regulating the PI3K/AKT pathway.

Sign in / Sign up

Export Citation Format

Share Document