Rosiglitazone attenuates early brain injury after experimental subarachnoid hemorrhage in rats

Gu, Chi; Wang, Yifei; Li, Jianru; Chen, Jingyin; Yan, Feng; Wu, Cheng Hsien; Gao, Chen

doi:10.1016/j.brainres.2015.07.025

Cited by 21 publications

(16 citation statements)

References 45 publications

(64 reference statements)

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“…PPARγ has been shown to play an essential role in regulating inflammatory response (Chawla, 2010; Croasdell et al, 2015; Jiang et al, 1998). After stroke, activation of PPARγ with its agonists significantly reduced the expression of pro-inflammatory mediators, and suppressed migration of macrophages and neutrophils into brain, as well as promoted phagocytosis-mediated hematoma resolution by promoting the M2 phagocytic phenotype of microglial cells, suggesting that PPARγ, a cytoprotective protein, exerted anti-inflammation property (Culman et al, 2007; Gliem et al, 2015; Gu et al, 2015; Kumari et al, 2010; Zhao et al, 2007; Zhao et al, 2015). In addition, PPARγ was also proven to prevent against the development of intracranial aneurysmal rupture (Shimada et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Netrin-1 binding UNC5B receptor attenuates neuroinflammation and brain injury via PPARγ/NFκB signaling pathway after subarachnoid hemorrhage in rats

Xie

Huang

Enkhjargal

et al. 2018

Brain, Behavior, and Immunity

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Neuroinflammation is an essential mechanism involved in the pathogenesis of subarachnoid hemorrhage (SAH)-induced brain injury. Recently, Netrin-1 (NTN-1) is well established to exert anti-inflammatory property in non-nervous system diseases through inhibiting infiltration of neutrophil. The present study was designed to investigate the effects of NTN-1 on neuroinflammation, and the potential mechanism in a rat model of SAH. Two hundred and ninety-four male Sprague Dawley rats (weight 280-330 g) were subjected to the endovascular perforation model of SAH. Recombinant human NTN-1 (rh-NTN-1) was administered intravenously. Small interfering RNA (siRNA) of NTN-1 and UNC5B, and a selective PPARγ antagonist bisphenol A diglycidyl ether (BADGE) were applied. Post-SAH evaluations included neurobehavioral function, brain water content, Western blot analysis, and immunohistochemistry. Our results showed that endogenous NTN-1 and its receptor UNC5B level were increased after SAH. Administration of rh-NTN-1 reduced brain edema, ameliorated neurological impairments, and suppressed microglia activation after SAH, which were concomitant with PPARγ activation, inhibition of NFκB, and decrease in TNF-α, IL-6, and ICAM-1, as well as myeloperoxidase (MPO). Knockdown of endogenous NTN-1 increased expression of pro-inflammatory mediators and MPO, and aggravated neuroinflammation and brain edema. Moreover, knockdown of UNC5B using specific siRNA and inhibition of PPARγ with BADGE blocked the protective effects of rh-NTN-1. In conclusion, our findings indicated that exogenous rh-NTN-1 treatment attenuated neuroinflammation and neurological impairments through inhibiting microglia activation after SAH in rats, which is possibly mediated by UNC5B/PPARγ/NFκB signaling pathway. Exogenous NTN-1 may be a novel therapeutic agent to ameliorating early brain injury via its anti-inflammation effect.

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Section: Discussionmentioning

confidence: 99%

Recombinant Netrin-1 binding UNC5B receptor attenuates neuroinflammation and brain injury via PPARγ/NFκB signaling pathway after subarachnoid hemorrhage in rats

Xie

Huang

Enkhjargal

et al. 2018

Brain, Behavior, and Immunity

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“…The Evan’s blue assay was performed to evaluate BBB permeability in SAP rats as described in a previous study [ 15 ]. A 2% Evan’s blue solution (5 mL/kg body weight, Sigma, USA) was injected via the femoral vein 1 h before sacrificing the rats.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model

Lin

Chen

et al. 2018

J Inflamm

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BackgroundImpairment of the blood-brain barrier (BBB) in severe acute pancreatitis (SAP) could result in life-threatening pancreatic encephalopathy. Interleukin-10 (IL-10) is a classical cytokine that is well-known for its strong immunoregulatory and anti-inflammatory abilities. However, whether and how IL-10 protects the BBB in SAP are still unclear.MethodsThis study includes in vivo experiments using a SAP rat model and in vitro experiments using an in vitro BBB model consisting of a monolayer of brain microvascular endothelial cells (BMECs). The study groups are divided into the control, SAP (in vivo)/TNF-α (in vitro), IL-10 treatment, IL-10 + signal transducer and activator of transcription 3 (STAT3) inhibitor S3I-201 treatment groups. Pancreatic pathological scores, serum amylase, serum TNF-α levels and BBB permeability by Evan’s blue assay in SAP rat models were evaluated. BMEC apoptosis in SAP rats or induced by TNF-αin vitro was detected by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and flow cytometry, separately. Expression levels of claudin-5 and proteins involved in the STAT3 signaling pathway were measured by Western blotting. Location and changes of junctional structure of claudin-5 on BMECs were assessed by immunohistochemistry and immunofluorescence.ResultsIn vivo, IL-10 alleviated the severity of inflammation, attenuated the increased BBB permeability in SAP rat models by reducing BMEC apoptosis via the STAT3 pathway and ameliorated the down-regulation of claudin-5 expression in BMECs; in vitro, IL-10 improved BBB integrity against TNF-α by attenuating BMEC apoptosis via the STAT3 pathway, the impairment of tight junction structure and the down-regulation of claudin-5 expression in BMECs.ConclusionsIL-10 improves BBB properties in SAP by attenuating the down-regulation of claudin-5 expression and the impairment of tight junctions and by STAT3 pathway-mediated anti-apoptotic effects on BMECs.

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“…As a peroxisome-proliferator-activated receptor- (PPAR-) γ agonist, rosiglitazone is not only an antidiabetic drug but also a neuroprotective agent, and it has shown various effects in treating brain ischemia [ 103 ], TBI [ 104 ], and SAH [ 105 ]. A study demonstrated rosiglitazone's ability to attenuate microglia/macrophage activation and neuronal loss after TBI [ 104 ].…”

Section: Polarization States Of Microglia In Tbi: Potential Therapmentioning

confidence: 99%

The Polarization States of Microglia in TBI: A New Paradigm for Pharmacological Intervention

Wang

et al. 2017

Neural Plasticity

Self Cite

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Traumatic brain injury (TBI) is a serious medical and social problem worldwide. Because of the complex pathophysiological mechanisms of TBI, effective pharmacotherapy is still lacking. The microglial cells are resident tissue macrophages located in the brain and have two major polarization states, M1 phenotype and M2 phenotype, when activated. The M1 phenotype is related to the release of proinflammatory cytokines and secondary brain injury, while the M2 phenotype has been proved to be responsible for the release of anti-inflammation cytokines and for central nervous system (CNS) repair. In animal models, pharmacological strategies inhibiting the M1 phenotype and promoting the M2 phenotype of microglial cells could alleviate cerebral damage and improve neurological function recovery after TBI. In this review, we aimed to summarize the current knowledge about the pathological significance of microglial M1/M2 polarization in the pathophysiology of TBI. In addition, we reviewed several drugs that have provided neuroprotective effects against brain injury following TBI by altering the polarization states of the microglia. We emphasized that future investigation of the regulation mechanisms of microglial M1/M2 polarization in TBI is anticipated, which could contribute to the development of new targets of pharmacological intervention in TBI.

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Rosiglitazone attenuates early brain injury after experimental subarachnoid hemorrhage in rats

Cited by 21 publications

References 45 publications

Recombinant Netrin-1 binding UNC5B receptor attenuates neuroinflammation and brain injury via PPARγ/NFκB signaling pathway after subarachnoid hemorrhage in rats

Recombinant Netrin-1 binding UNC5B receptor attenuates neuroinflammation and brain injury via PPARγ/NFκB signaling pathway after subarachnoid hemorrhage in rats

Interleukin-10 attenuates impairment of the blood-brain barrier in a severe acute pancreatitis rat model

The Polarization States of Microglia in TBI: A New Paradigm for Pharmacological Intervention

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