The GluN1/GluN2B NMDA receptor and metabotropic glutamate receptor 1 negative allosteric modulator has enhanced neuroprotection in a rat subarachnoid hemorrhage model

Zhang, Zongyong; Liu, Junke; Fan, Cundong; Mao, Leilei; Xie, Rongxia; Wang, Suyun; Yang, Mo; Yuan, Hui; Yang, Xiaoyi; Sun, Jingyi; Wang, Jian; Kong, Jiming; Huang, Siluo; Sun, Bo

doi:10.1016/j.expneurol.2017.12.005

Cited by 50 publications

(58 citation statements)

References 38 publications

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“…However, calcium overloading induces the activation of calpain 1 and 2, which has a deleterious effect on the brain (14,24). Previous studies have revealed that glutamate neurotoxicity is observed in EBI following experimental SAH (11,(25)(26)(27)(28), and that it causes an increase in the intracellular calcium concentration, predominantly through the N-methyl-D-aspartate receptor and the metabotropic glutamate receptor 1 (28), resulting in calpain activation. The western blotting results from the present study indicated that the expression of calpain 1 and 2 are increased after SAH compared with sham, which is consistent with the results of a previous study (13).…”

Section: Discussionmentioning

confidence: 99%

Calpastatin peptide attenuates early brain injury following experimental subarachnoid hemorrhage

et al. 2020

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Calpain activation may have an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The present study investigated the effects of the calpastatin peptide, a cell-permeable peptide that functions as a potent inhibitor of calpain, on EBI in a rat SAH model. It was revealed that calpastatin peptide treatment significantly reduced SAH-induced body weight loss and neurological deficit at 72 h when compared with untreated SAH controls. Furthermore, the quantification of brain water content and the extravasation of Evans blue dye revealed a significant reduction in SAH-induced brain edema and blood-brain barrier permeability at 72 h due to treatment with the calpastatin peptide when compared with untreated SAH controls. Finally, calpastatin peptide treatment significantly attenuated the protein levels of Bax, cytochrome c, cleaved caspase-9 and cleaved caspase-3, and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labelling-positive cells in the basal cortex at 72 h after SAH when compared with untreated SAH controls. These results indicated that the calpastatin peptide may ameliorate EBI following SAH in rat models.

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Section: Discussionmentioning

confidence: 99%

Calpastatin peptide attenuates early brain injury following experimental subarachnoid hemorrhage

et al. 2020

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“…A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) detection kit (Roche Inc., Indianapolis, USA) was used for TUNEL staining according to the manufacturer’s instructions [25,51]. Specifically, brain sections or cultured neurons were incubated with TUNEL reaction mixture for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Cerebroprotection by salvianolic acid B after experimental subarachnoid hemorrhage occurs via Nrf2- and SIRT1-dependent pathways

Zhang

et al. 2018

Free Radical Biology and Medicine

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Salvianolic acid B (SalB), a natural polyphenolic compound extracted from the herb of Salvia miltiorrhiza, possesses antioxidant and neuroprotective properties and has been shown to be beneficial for diseases that affect vasculature and cognitive function. Here we investigated the protective effects of SalB against subarachnoid hemorrhage (SAH)-induced oxidative damage, and the involvement of underlying molecular mechanisms. In a rat model of SAH, SalB inhibited SAH-induced oxidative damage. The reduction in oxidative damage was associated with suppressed reactive oxygen species generation; decreased lipid peroxidation; and increased glutathione peroxidase, glutathione, and superoxide dismutase activities. Concomitant with the suppressed oxidative stress, SalB significantly reduced neurologic impairment, brain edema, and neural cell apoptosis after SAH. Moreover, SalB dramatically induced nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation and increased expression of heme oxygenase-1 and NADPH: quinine oxidoreductase-1. In a mouse model of SAH, Nrf2 knockout significantly reversed the antioxidant effects of SalB against SAH. Additionally, SalB activated sirtuin 1 (SIRT1) expression, whereas SIRT1-specific inhibitor sirtinol pretreatment significantly suppressed SalB-induced SIRT1 activation and Nrf2 expression. Sirtinol pretreatment also reversed the antioxidant and neuroprotective effects of SalB. In primary cultured cortical neurons, SalB suppressed oxidative damage, alleviated neuronal degeneration, and improved cell viability. These beneficial effects were associated with activation of the SIRT1 and Nrf2 signaling pathway and were reversed by sirtinol treatment. Taken together, these in vivo and in vitro findings suggest that SalB provides protection against SAH-triggered oxidative damage by upregulating the Nrf2 antioxidant signaling pathway, which may be modulated by SIRT1 activation.

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“… 2 GluN2A and GluN2B are two of the best characterized regulatory subunits that play important but distinct roles in development and synaptic plasticity. 3 – 5 Neuronal apoptosis is prevented when GluN2A subunit-containing NMDARs (GluN2ARs) is selectively activated, 6 , 7 whereas the activation of GluN2B subunit-containing NMDARs (GluN2BRs) is associated with inflammatory pain. Previous study also demonstrated that intraperitoneal injection of GluN2B antagonists relieved the chronic inflammatory pain.…”

Section: Introductionmentioning

confidence: 99%

Tetrahydroxystilbene glucoside relieves the chronic inflammatory pain by inhibiting neuronal apoptosis, microglia activation, and GluN2B overexpression in anterior cingulate cortex

Fan

Guan

et al. 2018

Mol Pain

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Tetrahydroxystilbene glucoside (THSG) is one of the active ingredients of Polygonum multiflorum. It has been shown to exert a variety of pharmacological effects, including antioxidant, anti-aging, and anti-atherosclerosis. Because of its prominent anti-inflammatory effect, we explored whether THSG had analgesic effect. In this study, we used a model of chronic inflammatory pain caused by injecting complete Freund’s adjuvant into the hind paw of mice. We found THSG relieved swelling and pain in the hind paw of mice on a dose-dependent manner. In the anterior cingulate cortex, THSG suppressed the upregulation of GluN2B-containing N-methyl-D-aspartate receptors and the downregulation of GluN2A-containing N-methyl-D-aspartate receptors caused by chronic inflammation. In addition, THSG increased Bcl-2 and decreased Bax and Caspase-3 expression by protecting neuronal survival. Furthermore, THSG inhibited the phosphorylation of p38 and the increase of nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α). Immunohistochemical staining revealed that THSG blocked the activation of microglia and reduced the release of proinflammatory cytokines TNF-α, interleukin 1β (IL-1β), and interleukin 6 (IL-6). In conclusion, this study demonstrated that THSG had a certain effect on alleviating complete Freund’s adjuvant-induced chronic inflammatory pain.

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The GluN1/GluN2B NMDA receptor and metabotropic glutamate receptor 1 negative allosteric modulator has enhanced neuroprotection in a rat subarachnoid hemorrhage model

Cited by 50 publications

References 38 publications

Calpastatin peptide attenuates early brain injury following experimental subarachnoid hemorrhage

Calpastatin peptide attenuates early brain injury following experimental subarachnoid hemorrhage

Cerebroprotection by salvianolic acid B after experimental subarachnoid hemorrhage occurs via Nrf2- and SIRT1-dependent pathways

Tetrahydroxystilbene glucoside relieves the chronic inflammatory pain by inhibiting neuronal apoptosis, microglia activation, and GluN2B overexpression in anterior cingulate cortex

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