Neuroprotective effects of four different fluids on cerebral ischaemia/reperfusion injury in rats through stabilization of the blood–brain barrier

Shan, Reai; Zhou, Hongyan; Liu, Xinfang; Su, Guangjun; Liu, Guangsen; Zhang, Xiaoli; Sun, Cong; Yu, Zining; Zhan, Ling; Huang, Zhihua

doi:10.1111/ejn.15385

Cited by 9 publications

(5 citation statements)

References 70 publications

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“…The rat tMCAO model was constructed using the modified Zea Longa suture method as described previously (Li et al 2017 ; Liu et al 2017 , 2021 ; Shan et al 2021 ). Rats were anesthetized by administering an intraperitoneal injection of 1% pentobarbital sodium at a dose of 4.5 mL/kg.…”

Section: Methodsmentioning

confidence: 99%

Icaritin inhibits neuroinflammation in a rat cerebral ischemia model by regulating microglial polarization through the GPER–ERK–NF-κB signaling pathway

Zhang

et al. 2022

Mol Med

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Background Activated microglia play a key role in initiating the inflammatory cascade following ischemic stroke and exert proinflammatory or anti-inflammatory effects, depending on whether they are polarized toward the M1 or M2 phenotype. The present study investigated the regulatory effect of icaritin (ICT) on microglial polarization in rats after cerebral ischemia/reperfusion injury (CI/RI) and explored the possible anti-inflammatory mechanisms of ICT. Methods A rat model of transient middle cerebral artery occlusion (tMCAO) was established. Following treatment with ICT, a G protein-coupled estrogen receptor (GPER) inhibitor or an extracellular signal-regulated kinase (ERK) inhibitor, the Garcia scale and rotarod test were used to assess neurological and locomotor function. 2,3,5-Triphenyltetrazolium chloride (TTC) and Fluoro-Jade C (FJC) staining were used to evaluate the infarct volume and neuronal death. The levels of inflammatory factors in the ischemic penumbra were evaluated using enzyme-linked immunosorbent assays (ELISAs). In addition, western blotting, immunofluorescence staining and quantitative PCR (qPCR) were performed to measure the expression levels of markers of different microglial phenotypes and proteins related to the GPER–ERK–nuclear factor kappa B (NF-κB) signaling pathway. Results ICT treatment significantly decreased the cerebral infarct volume, brain water content and fluorescence intensity of FJC; improved the Garcia score; increased the latency to fall and rotation speed in the rotarod test; decreased the levels of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), Iba1, CD40, CD68 and p-P65-NF-κB; and increased the levels of CD206 and p-ERK. U0126 (an inhibitor of ERK) and G15 (a selective antagonist of GPER) antagonized these effects. Conclusions These findings indicate that ICT plays roles in inhibiting the inflammatory response and achieving neuroprotection by regulating GPER–ERK–NF-κB signaling and then inhibiting microglial activation and M1 polarization while promoting M2 polarization, which provides a new therapeutic for against cerebral ischemic stroke. Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

Icaritin inhibits neuroinflammation in a rat cerebral ischemia model by regulating microglial polarization through the GPER–ERK–NF-κB signaling pathway

Zhang

et al. 2022

Mol Med

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“…Microglia and astrocytes express a diverse set of TLRs [40]. NF-kB is a transcription factor linked to inflammation, oxidative damage, and apoptosis [40]. Our results showed that the brain tissues of the IR mice showed significantly higher mRNA expression of TLR2, TLR4, NF-kB, TNF-α, IL-6, and IL-1β.…”

Section: Discussionmentioning

confidence: 72%

“…TLR2 and TLR4 trigger the transcription factor NF-kB and increase the production of inflammatory cytokines [39]. Microglia and astrocytes express a diverse set of TLRs [40]. NF-kB is a transcription factor linked to inflammation, oxidative damage, and apoptosis [40].…”

Section: Discussionmentioning

confidence: 99%

“…The brain was extracted from the skull and fixed overnight at 4 • C with 4% PFA. Each fixed tissue was dehydrated via an upgraded ethanol series (40,60,70,80,90, and 100%, 60 min/each), cleared in xylene, and embedded and blocked in liquid paraffin wax. After that, serial coronal sections with a 5 µm thickness were obtained from each brain using a microtome, deparaffinized using xylene, progressively dehydrated with ethanol (100, 95, 70, and 50%, with 5 min/each), and rinsed in distilled water for five minutes.…”

Section: Histological Examinationmentioning

confidence: 99%

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The Effect of Cerebrolysin in an Animal Model of Forebrain Ischemic-Reperfusion Injury: New Insights into the Activation of the Keap1/Nrf2/Antioxidant Signaling Pathway

Marghani

Rezk

Ateya

et al. 2023

IJMS

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Forebrain ischemia-reperfusion (IR) injury causes neurological impairments due to decreased cerebral autoregulation, hypoperfusion, and edema in the hours to days following the restoration of spontaneous circulation. This study aimed to examine the protective and/or therapeutic effects of cerebrolysin (CBL) in managing forebrain IR injury and any probable underlying mechanisms. To study the contribution of reperfusion to forebrain injury, we developed a transient dual carotid artery ligation (tDCAL/IR) mouse model. Five equal groups of six BLC57 mice were created: Group 1: control group (no surgery was performed); Group 2: sham surgery (surgery was performed without IR); Group 3: tDCAL/IR (surgery with IR via permanently ligating the left CA and temporarily closing the right CA for 30 min, followed by reperfusion for 72 h); Group 4: CBL + tDCAL/IR (CBL was given intravenously at a 60 mg/kg BW dose 30 min before IR); and Group 5: tDCAL/IR + CBL (CBL was administered i.v. at 60 mg/kg BW three hours after IR). At 72 h following IR, the mice were euthanized. CBL administration 3 h after IR improved neurological functional recovery, enhanced anti-inflammatory and antioxidant activities, alleviated apoptotic neuronal death, and inhibited reactive microglial and astrocyte activation, resulting in neuroprotection after IR injury in the tDCAL/IR + CBL mice group as compared to the other groups. Furthermore, CBL reduced the TLRs/NF-kB/cytokines while activating the Keap1/Nrf2/antioxidant signaling pathway. These results indicate that CBL may improve neurologic function in mice following IR.

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“…The rat tMCAO model was constructed by the modi ed Zea Longa suture method as described previously (Li et al, 2017;Liu et al, 2021;Shan et al, 2021). Rats were anesthetized by intraperitoneal injection of 1% pentobarbital sodium at a dose of 4.5 mL/kg.…”

Section: Transient Middle Cerebral Artery Occlusion (Tmcao) Modelmentioning

confidence: 99%

Icaritin inhibits neuroinflammation by regulating microglial polarization through GPER-ERK-NF-κB signaling pathway in cerebral ischemic rat

Zhang

et al. 2022

Preprint

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BackgroundActivated microglia play a key role in initiating the in ammatory cascade following ischemic stroke and exert proin ammatory or anti-in ammatory effects depending on whether they are polarized toward the M1 or M2 phenotype. The present study investigated the regulatory effect of Icaritin (ICT) on microglial polarization in rats after cerebral ischemia/reperfusion injury (CI/RI) and explored the possible antiin ammatory mechanisms of ICT. MethodsA rat model of transient middle cerebral artery occlusion (tMCAO) was established. Following treatment with ICT, a G protein coupled estrogen receptor (GPER) inhibitor or an extracellular signal regulated kinase (ERK) inhibitor, the Garcia scale and rotarod test were used to assess neurological and locomotor function. 2,3,5-Triphenyltetrazolium chloride (TTC) and Fluoro-Jade C (FJC) staining were used to evaluate the infarct volume and neuronal death. The levels of in ammatory factors in the ischemic penumbra were evaluated by enzyme-linked immunosorbent assay (ELISA). In addition, Western blotting, immuno uorescence and quantitative PCR (qPCR) were used to measure the expression levels of markers of different microglial phenotypes and proteins related to the GPER-ERK-NF-κB signaling pathway. ResultsWe found that ICT treatment signi cantly decreased the cerebral infarct volume, brain water content and uorescence intensity of FJC; improved the Garcia score; increased the latency to fall and rotation speed in the rotarod test; inhibited the expression of IL-1β, TNF-α, Iba1, CD40, CD68 and p-P65-NF-κB; and increased the levels of CD206 and p-ERK. U0126 (an inhibitor of ERK) and G15 (a selective antagonist of GPER) antagonized these effects. ConclusionsThese ndings indicate that ICT plays roles in inhibiting the in ammatory response and achieving neuroprotection by regulating GPER-ERK-NF-κB signaling and then inhibits microglial activation and M1 polarization while promoting M2 polarization, which provides new therapeutic strategy against cerebral ischemia stroke.

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Neuroprotective effects of four different fluids on cerebral ischaemia/reperfusion injury in rats through stabilization of the blood–brain barrier

Cited by 9 publications

References 70 publications

Icaritin inhibits neuroinflammation in a rat cerebral ischemia model by regulating microglial polarization through the GPER–ERK–NF-κB signaling pathway

Icaritin inhibits neuroinflammation in a rat cerebral ischemia model by regulating microglial polarization through the GPER–ERK–NF-κB signaling pathway

The Effect of Cerebrolysin in an Animal Model of Forebrain Ischemic-Reperfusion Injury: New Insights into the Activation of the Keap1/Nrf2/Antioxidant Signaling Pathway

Icaritin inhibits neuroinflammation by regulating microglial polarization through GPER-ERK-NF-κB signaling pathway in cerebral ischemic rat

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