Rab7b Overexpression–Ameliorated Ischemic Brain Damage Following tMCAO Involves Suppression of TLR4 and NF-κB p65

Qi, Jinlong; Rong, Yanhong; Wang, Lu; Xu, Jiankun; Zhao, Kun

doi:10.1007/s12031-019-01295-y

Cited by 23 publications

(11 citation statements)

References 36 publications

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“…NF-κB, a central transcription factor of in ammatory response, is required for the transcriptional induction of many pro-in ammatory mediators, which was implicated to potentially regulate the in ammatory processes in ischemic stroke [43]. In consistent with our data, downregulation of TLR4 and NF-κB p65 contributed to the ameliorated ischemic brain injury by Rab7b in rats after transient tMCAO treatment [44].…”

Section: Discussionsupporting

confidence: 87%

Neuroprotective Effects of microRNA-140-5p on Ischemic Stroke in Mice via its Regulation on the TLR4/NF-κB Axis

Song

Wang

Shi

et al. 2020

Preprint

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Background and aim: Ischemic stroke is one of the main causes of death worldwide and permanent global disability. On the basis of existing literature data, we carried out studies in an effort to explore how miR-140-5p affects ischemic stroke and whether the mechanism relates to toll-like receptor-4 (TLR4) and nuclear factor-kappa B (NF-κB).Methods: Middle cerebral artery occlusion (MCAO) was employed to establish a mouse model of ischemic stroke in vivo, while primary neurons were exposed to oxygen-glucose deprivation (OGD) to set up an ischemic stroke model in vitro. RT-qPCR was performed to detect the miR-140-5p expression and Western blot was employed to detect the expression TLR4, NF-κB, and apoptosis-related factors. Then, based gain-function of experiments using miR-140-5p mimic and TLR4 overexpression plasmid, neurological function score, TTC staining, TUNEL staining, as well as flow cytometry were carried out to evaluate the effects of miR-140-5p and TLR4 on MCAO mice and OGD neurons. Meanwhile, dual-luciferase reporter assay was used to validate the relationship between miR-140-5p and TLR4.Results: miR-140-5p expressed at a low level and TLR4 at a high level in ischemic stroke. It was verified that miR-140-5p targeted TLR4 and downregulated its expression. miR-140-5p overexpression was observed to inhibit the apoptosis of neurons under OGD exposure and restrain the progression of ischemic stroke, while TLR4 overexpression promoted the apoptosis and disease progression. Besides, miR-140-5p overexpression led to a decrease in NF-κB protein level, which was increased by TLR4 overexpression. Conclusion: In conclusion, from our data we conclude that miR-140-5p overexpression may be instrumental for the therapeutic targeting of ischemic stroke by alleviating neuron injury with the involvement of TLR4/NF-κB axis.

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Section: Discussionsupporting

confidence: 87%

Neuroprotective Effects of microRNA-140-5p on Ischemic Stroke in Mice via its Regulation on the TLR4/NF-κB Axis

Song

Wang

Shi

et al. 2020

Preprint

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“…Inhibition of NF-κB expression reduced cerebral infarction area and neuronal death in MCAO rats [27]. Among these neuroinflammatory events, those elicited through NF-κB p65 play an important role in the induction of excessive production of inflammatory factors and ischemic brain damage, as evidenced by previous studies showing that downstream NF-κB p65 protects the brain from ischemic damage and neurodegeneration in MCAO rats [28]. This study found that the expression of NF-κB p65 in the model group was significantly increased, indicating that NF-κp p65 was activated and translocated into the nucleus.…”

Section: Discussionmentioning

confidence: 82%

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

Liang

Yang

et al. 2020

Bioscience Reports

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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.

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“…9) In general, activated microglia releasing inflammatory cytokines is considered to be involved in the exacerbation of functional recovery after stroke and in the development of chronic pain. 10,25,26) Therefore, it was possible that the upregulation of spinal DDAH1 may be induced by microglial activation, which was observed in BCAO model mice. Next, we found that the i.t.…”

Section: Discussionmentioning

confidence: 99%

The Involvement of DDAH1 in the Activation of Spinal NOS Signaling in Early Stage of Mechanical Allodynia Induced by Exposure to Ischemic Stress in Mice

Matsuura

Nakamoto

Tokuyama

2019

Biological & Pharmaceutical Bulletin

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The pathophysiological mechanism of central post-stroke pain (CPSP) is complicated and not well understood. Recently, it has been reported that an increase in the levels of spinal nitric oxide synthetase (NOS) occurs in cerebral ischemia, and spinal NOS is involved in the development of neuropathic pain. The aim of this study was to elucidate the mechanism of spinal NOS signaling in the development of CPSP. Male ddY mice were subjected to 30-min long bilateral carotid artery occlusion (BCAO). The withdrawal responses to mechanical stimuli were significantly increased as determined with von Frey test on days 1 and 3 after BCAO. Protein expression of spinal N (G) ,N (G)-dimethylarginine dimethylaminohydralase 1 (DDAH1), a key enzyme involved in the metabolism of the endogenous NOS, increased on day 1 after BCAO, but not on day 3. Intrathecal (i.t.) injection of PD404182, a DDAH1 inhibitor, significantly suppressed mechanical allodynia on day 1, but not on day 3 after BCAO. In addition, i.t. administration of N G-nitro-L-arginine methyl ester (L-NAME), a non-selective NOS inhibitor, significantly blocked mechanical allodynia on days 1 and 3 after BCAO. Furthermore, BCAO-induced increment of spinal NOS activity was inhibited by the pretreatment with PD404182. These results suggest that mechanical allodynia in the early stage of CPSP is caused by increment of NOS activity through upregulated DDAH1 in the spinal cord.

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Rab7b Overexpression–Ameliorated Ischemic Brain Damage Following tMCAO Involves Suppression of TLR4 and NF-κB p65

Cited by 23 publications

References 36 publications

Neuroprotective Effects of microRNA-140-5p on Ischemic Stroke in Mice via its Regulation on the TLR4/NF-κB Axis

Neuroprotective Effects of microRNA-140-5p on Ischemic Stroke in Mice via its Regulation on the TLR4/NF-κB Axis

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

The Involvement of DDAH1 in the Activation of Spinal NOS Signaling in Early Stage of Mechanical Allodynia Induced by Exposure to Ischemic Stress in Mice

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