scholarly journals Ghrelin reduces cerebral ischemic injury in rats by reducing M1 microglia/macrophages

2022 ◽  
Vol 66 (1) ◽  
Author(s):  
Rong Tian ◽  
Gengsheng Mao
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Infarct Volume ◽  
Neurological Function ◽  
Tunel Staining ◽  
Triphenyltetrazolium Chloride ◽  
Ischemic Brain ◽  
Tnf Α ◽  
Ischemic Brain Tissue ◽  
The Brain

The purpose of this study was to investigate the effect of Ghrelin on the polarization of microglia/ macrophages after cerebral ischemia (CI) in rats. 60 wild-type SD rats were randomly divided into sham group, CI group, CI+Ghrelin group, 20 rats in each group. The modified Longa suture method was used to establish the middle cerebral artery occlusion (MCAO) model in rats. Before surgery, Ghrelin was injected subcutaneously (100μg/kg, twice a day) for 4 consecutive weeks. After modeling, neurological function scores were performed with three behavioral experiments: mNSS score, Corner test, and Rotarod test, to evaluate the recovery of neurological function after Ghrelin treatment. At the same time, the brain tissues were collected and stained with 2,3,5-triphenyltetrazolium chloride (TTC) to detect the cerebral infarct volume. RT-qPCR was used to detect the expression of TNF-α and IL-1β in the ischemic brain tissue, and the TUNEL staining was used to detect the apoptosis of brain tissue. Flow cytometry was used to detect the percentage of M1 type microglia/macrophages which were isolated by trypsin digestion of fresh cerebral cortex. Then, the Western blotting and immunofluorescence method were used to detect the phosphorylation level of AKT (P-AKT) and AKT. Compared with the CI group, the neurological function of the rats in the CI+Ghrelin group was dramatically improved, and the cerebral infarction area was dramatically reduced. At the same time, the expression of TNF-α and IL-1β in the ischemic brain tissue of rats in the CI+Ghrelin group decreased, and the apoptotic cells in the brain tissue also decreased. Compared with the CI treatment group, the activation of M1 microglia/macrophages in the cortex of the ischemic side of the infarct and the peri-infarct area in the CI+Ghrelin group was dramatically inhibited. At the same time, the ratio of P-AKT/AKT of the brain tissue in the CI+Ghrelin group was dramatically higher than that of the CI group. In the rat cerebral ischemia model, Ghrelin can promote the repair of brain damage and the recovery of neurological function after ischemia. Its mechanism may be related to activating AKT to selectively reduce M1 microglia/macrophages, reducing inflammation and cell apoptosis in brain tissue.

Abstract W MP81: Excess Salt Increases Infarct Size Produced by Photothrombotic Middle Cerebral Artery Occlusion Without Increasing Blood Pressure in Spontaneously Hypertensive Rats

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Hiroshi Yao ◽  
Toru Nabika
Keyword(s):  
Infarct Size ◽  
Brain Tissue ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Control Group ◽  
Salt Loading ◽  
Ischemic Brain ◽  
Spontaneously Hypertensive ◽  
Ischemic Brain Tissue ◽  
Cerebral Artery Occlusion

Background and Purpose: Cerebral circulation is known to be vulnerable to excess salt (e.g., impaired vasodilation, increased oxidative stress, accelerated spontaneous stroke, and enhanced blood-brain barrier [BBB] disruption). To our knowledge, however, no study has investigated the effects of excess salt on focal ischemic injury. Methods: After 14 days of salt loading or water, spontaneously hypertensive rats (SHR, Izumo strain, n=43) or normotensive Wistar-Kyoto rats (WKY, n=11) were subjected to photothrombotic middle cerebral artery occlusion (MCAO), and infarct volume was determined at 48 h after MCAO. Brain albumin and hemoglobin contents, as indices of BBB disruption, were determined with SELDI-TOF-MS in ischemic brain tissue. Effects of excess salt on the lower limits of cerebral blood flow (CBF) autoregulation were also determined. Results: Two-way analysis of variance confirmed a significant effect of saline on the volumes of drinking in SHR (p=0.000). Resting mean arterial blood pressure (BP) in SHR was 137±15 (S.D.) mmHg and 141±7 mmHg in the salt loading and control groups, respectively. After MCAO, regional CBF, determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning), was more steeply decreased in the salt-loaded group than in the control group. In SHR, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p=0.002), while albumin and hemoglobin levels in discrete brain regions were not different between the groups. In WKY, salt loading did not significantly increase infarct size. CBF response to hemorrhagic hypotension (i.e., autoregulation) was not affected by excess salt. Conclusions: We demonstrated that excess salt increased infarct size produced by photothrombotic MCAO without increasing BP in SHR but not in WKY. Excess salt did not deteriorate both vasogenic edema and hemorrhagic transformation of ischemic brain tissue after MCAO. The detrimental effects of excess salt were considered to be the result of compromised CBF in the ischemic brain tissue supplied by collateral circulation. A future study will investigate the mechanisms underlying the salt sensitivity to focal brain ischemia independent of BP changes.

scholarly journals Parthenolide Is Neuroprotective in Rat Experimental Stroke Model: Downregulating NF-κB, Phospho-p38MAPK, and Caspase-1 and Ameliorating BBB Permeability

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lipeng Dong ◽  
Huimin Qiao ◽  
Xiangjian Zhang ◽  
Xiaolin Zhang ◽  
Chaohui Wang ◽  
...  
Keyword(s):  
Western Blot ◽  
Water Content ◽  
Brain Tissue ◽  
Neurological Deficit ◽  
Infarct Volume ◽  
Brain Water Content ◽  
Ischemic Brain ◽  
Caspase 1 ◽  
Ischemic Brain Tissue ◽  
Brain Water

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Parthenolide (PN) has been proved to elicit a wide range of biological activities through its anti-inflammatory action in the treatment of migraine, arthritis, and atherosclerosis. To decide whether this effect applies to ischemic injury in brain, we therefore investigate the potential neuroprotective role of PN and the underlying mechanisms. Male Sprague-Dawley rats were randomly divided into Saline, Vehicle, and PN groups and a permanent middle cerebral artery occlusion (MCAO) model was used. PN administered intraperitoneally immediately after cerebral ischemia and once daily on the following days. At time points after MCAO, neurological deficit, infarct volume, and brain water content were measured. Immunohistochemistry, western blot and RT-PCR were used to analyze the expression of NF-κB and caspase-1 in ischemic brain tissue. Phospho-p38MAPK and claudin-5 were detected by western blot. The results indicated that PN dramatically ameliorated neurological deficit, brain water content, and infarct volume, downregulated NF-κB, phospho-p38MAPK, and caspase-1 expressions, and upregulated claudin-5 expression in ischemic brain tissue.Conclusions.PN protected the brain from damage caused by MCAO; this effect may be through downregulating NF-κB, phosho-p38MAPK, and caspase-1 expressions and ameliorating BBB permeability.

scholarly journals Stigmasterol alleviates cerebral ischemia/reperfusion injury by attenuating inflammation and improving antioxidant defenses in rats

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Qilong Liang ◽  
Jun Yang ◽  
Jiaji He ◽  
Xiaoling Chen ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Antioxidant Defenses ◽  
Neurological Deficits ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Heme Oxygenase 1 ◽  
Cerebral Ischemia Reperfusion

Abstract Background/aims: The paper aimed to investigate the effects of Stigmasterol on inflammatory factors, antioxidant capacity, and apoptotic signaling pathways in brain tissue of rats with cerebral ischemia/reperfusion (I/R) injury. Methods: The neurological deficits of the rats were analyzed and HE staining was performed. The cerebral infarct volume was calculated by means of TTC staining, and neuronal apoptosis was detected by TUNEL staining. At the same time, the contents of glutathione peroxidase, glutathione, superoxide dismutase (SOD), nitric oxide, and malondialdehyde in brain tissue were measured. The expression of the relevant protein was detected by means of Western blotting. Results: The results showed that the neurological deficit score and infarct area of the I/R rats in the soy sterol treatment group were significantly lower than those in the I/R group. Moreover, the levels of carbon monoxide and malondialdehyde in the soysterol group were significantly lower than those in the I/R group, and the expressions of cyclooxygenase-2 (Cox-2) and NF-κB (p65) in the soysterol group were also significantly lower than those in the I/R group. The expression of Nrf2 (nucleus) and heme oxygenase-1 (HO-1) increased significantly, and the activities of antioxidant enzymes and SOD were increased. In addition, the stigmasterol treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, and up-regulate Bcl-Xl expression. Conclusion: Stigmasterol protects the brain from brain I/R damage by reducing oxidative stress and inflammation.

scholarly journals Prevention of JNK Phosphorylation as a Mechanism for Rosiglitazone in Neuroprotection after Transient Cerebral Ischemia: Activation of Dual Specificity Phosphatase

2012 ◽  
Vol 33 (1) ◽  
pp. 106-114 ◽  
Author(s):  
Nobuya Okami ◽  
Purnima Narasimhan ◽  
Hideyuki Yoshioka ◽  
Hiroyuki Sakata ◽  
Gab Seok Kim ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Cortical Neurons ◽  
Neuroprotective Effect ◽  
Mitogen Activated Protein Kinase ◽  
Ischemic Brain ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Pparγ Agonist ◽  
Ischemic Brain Tissue

Rosiglitazone, a synthetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist, prevents cell death after cerebral ischemia in animal models, but the underlying mechanism has not been clarified. In this study, we examined how rosiglitazone protects neurons against ischemia. Mice treated with rosiglitazone were subjected to 60 minutes of focal ischemia followed by reperfusion. Rosiglitazone reduced infarct volume after ischemia and reperfusion. We show that this neuroprotective effect was reversed with a PPARgM antagonist. Western blot analysis showed a significant increase in expression of phosphorylated stress-activated protein kinases (c-Jun N-terminal kinase (JNK) and p38) in ischemic brain tissue. Rosiglitazone blocked this increase. Furthermore, we observed that rosiglitazone increased expression of the dual-specificity phosphatase 8 (DUSP8) protein and messenger RNA in ischemic brain tissue. Dual-specificity phosphatase 8 is a mitogen-activated protein kinase phosphatase that can dephosphorylate JNK and p38. Another key finding of the present study was that knockdown of DUSP8 in primary cultured cortical neurons that were subjected to oxygen–glucose deprivation diminished rosiglitazone's effect on downregulation of JNK phosphorylation. Thus, rosiglitazone's neuroprotective effect after ischemia is mediated by blocking JNK phosphorylation induced by ischemia via DUSP8 upregulation.

Long-Term Administration of Polygonum multiflorum Thunb: Reduces Cerebral Ischemia-induced Infarct Volume in Gerbils

2003 ◽  
Vol 31 (01) ◽  
pp. 71-77 ◽  
Author(s):  
Yin-Ching Chan ◽  
Ming-Fu Wang ◽  
Ya-Ching Chen ◽  
Dar-Yu Yang ◽  
Ming-Shih Lee ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ethanol Extract ◽  
Polygonum Multiflorum ◽  
Triphenyltetrazolium Chloride ◽  
Term Administration ◽  
The Brain

Focal cerebral ischemia was produced by an occlusion of the middle cerebral artery for 1, 3 and 24 hours in gerbils. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride (TTC) transcardiac perfusion 24 hours after cerebral ischemia. Significant and consistent infarct sizes were produced in gerbils subjected to 24-hour occlusion of the middle cerebral arterey when compared to the 1 and 3-hour occlusion groups. Long term pretreatment of the 50% ethanol extract of Polygonum multiflorum Thunb. for 2 weeks significantly reduced the infarct volume by 50% as compared to that of the 24-hour occlusion group. The results revealed that long term pretreatment of Polygonum multiflorum Thunb. may protect the brain against focal cerebral ischemia.

scholarly journals Pomalidomide Reduces Ischemic Brain Injury in Rodents

2019 ◽  
Vol 28 (4) ◽  
pp. 439-450 ◽  
Author(s):  
Yan-Rou Tsai ◽  
David Tweedie ◽  
Ignacio Navas-Enamorado ◽  
Michael T. Scerba ◽  
Cheng-Fu Chang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Infarct Volume ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Artery Occlusion ◽  
Mitochondrial Activity ◽  
Pharmacokinetic Studies ◽  
Ischemic Brain ◽  
Tnf Α

Stroke is a leading cause of death and severe disability worldwide. After cerebral ischemia, inflammation plays a central role in the development of permanent neurological damage. Reactive oxygen species (ROS) are involved in the mechanism of post-ischemic inflammation. The activation of several inflammatory enzymes produces ROS, which subsequently suppress mitochondrial activity, leading to further tissue damage. Pomalidomide (POM) is a clinically available immunomodulatory and anti-inflammatory agent. Prior cellular studies demonstrate that POM can mitigate oxidative stress and lower levels of pro-inflammatory cytokines, particularly TNF-α, which plays a prominent role in ischemic stroke-induced brain damage and functional deficits. To evaluate the potential value of POM in cerebral ischemia, POM was initially administered to transgenic mice chronically over-expressing TNF-α surfactant protein (SP)-C promoter (SP-C/TNF-α mice) to assess whether systemically administered drug could lower systemic TNF-α level. POM significantly lowered serum levels of TNF-α and IL-5. Pharmacokinetic studies were then undertaken in mice to evaluate brain POM levels following systemic drug administration. POM possessed a brain/plasma concentration ratio of 0.71. Finally, rats were subjected to transient middle cerebral artery occlusion (MCAo) for 60 min, and subsequently treated with POM 30 min thereafter to evaluate action on cerebral ischemia. POM reduced the cerebral infarct volume in MCAo-challenged rats and improved motor activity, as evaluated by the elevated body swing test. POM’s neuroprotective actions on ischemic injury represent a potential therapeutic approach for ischemic brain damage and related disorders, and warrant further evaluation.

Effects of near-far acupuncture on neuronal function and expression of apoptosis-related protein Bax/Bcl-2/Cleaved caspase-3 in rats with ischemic stroke

2021 ◽  
Vol 45 (2) ◽  
pp. 73-86
Author(s):  
Wang Jian ◽  
Zhang Can ◽  
Yang Jun ◽  
Xing Liwei ◽  
Zhang Kun ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Brain Tissue ◽  
Caspase 3 ◽  
Neurological Function ◽  
Acupuncture Group ◽  
Sham Operation ◽  
Model Group ◽  
Ischemic Brain ◽  
Ischemic Brain Tissue

Objectives To explore the effects of electroacupuncture on nerve function in rats with ischemic stroke and its mechanism of anti-apoptosis. Methods A total of 80 SPF male SD rats were randomly divided into sham operation group, model group, sham electroacupuncture group, acupuncture group, electroacupuncture group and 16 rats in each group. The rat model of left ischemic stroke was prepared by suture embolization. In the sham group, the left common carotid artery was isolated only and no other treatment was given. In the electroacupuncture group, "Baihui" and "Mingmen" were selected for acupuncture, followed by dilatation wave, frequency 2Hz/100Hz, intensity 1mA, and electroacupuncture for 30min. The sham electroacupuncture group was the same as the electroacupuncture group in acupoint electroacupuncture group was the same as the electroacupuncture group in acupoint selection. The electroacupuncture group was only inserted subcutaneously and then connected with the electroacupuncture group without power supply, and fixed for 30 minutes. The electroacupuncture group and the acupuncture group received electroacupuncture treatment once, for a total of 14 days, 1d after modeling. The Improved Neurological Impairment scale (mNSS) was used to evaluate the degree of neurological impairment in each group after anesthesia and wakefulness. The percentage of cerebral infarction area was determined by TTC staining. HE staining and Nissl staining were used to observe the pathological changes of ischemic brain tissue. The level of apoptosis in ischemic brain tissue was detected by TUNEL assay. Western blot was used to detect protein expression of Bax, Bcl-2 and Cleaved caspase-3 in ischemic brain tissue. Results Compared with the sham operation group, neurological function score, percentage of cerebral infarction area and apoptosis level in the model group were significantly increased (all P < 0.01). Compared with the model group, neurological function score, percentage of cerebral infarction area and apoptosis index of acupuncture group and electroacupuncture group were decreased (all P <0.05). Compared with the model group, the expression levels of Bcl-2 protein in ischemic brain tissue of rats with ischemic stroke were up-regulated in the acupuncture group and electroacupuncture group to different degrees, while the expression levels of Bax and Cleaved caspase-3 protein were down-regulated in the electroacupuncture group. Conclusion Electroacupuncture may inhibit Bax, Cleaved caspase-3 and up-regulate the expression of Bcl-2 against neuronal apoptosis, thereby improving the neurological function injury of ischemic stroke rats.

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