Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage

Wu, Qingzhong; Qi, Lifeng; Li, Hanxia; Mao, Leilei; Yang, Mo; Xie, Rongxia; Yang, Xiaoyi; Wang, Jian; Zhang, Zongyong; Kong, Jiming; Sun, Bo

doi:10.1007/s10753-017-0567-8

Cited by 34 publications

(28 citation statements)

References 24 publications

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“…BBB permeability. The permeability of the BBB was assessed using Evans blue extravasation as previously reported (22,23). Briefly, rats were anesthetized with 40 mg/kg pentobarbital (intraperitoneal) at 71 h after SAH and 2% Evans Blue dye (5 ml/kg) was injected into the right femoral vein.…”

Section: Methodsmentioning

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: Methodsmentioning

confidence: 99%

Calpastatin peptide attenuates early brain injury following experimental subarachnoid hemorrhage

et al. 2020

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“…SAH was induced in rats by a single blood injection, as described previously with some modification [4,34]. Briefly, rats were anesthetized with 10% chloral hydrate (0.35 mL/100 g).…”

Section: Methodsmentioning

confidence: 99%

“…Body weight change was expressed as a ratio of body weight after surgery to body weight before surgery [34,38]. …”

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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“…Currently, early brain injury (EBI) is one of the key mechanisms of SAH and plays a critical role in high mortality and disability after SAH (Sehba et al, 2011 ; Chen et al, 2014 ; Yuan et al, 2017 ). A growing body of evidence indicates that inflammatory injury plays pivotal roles in the EBI pathogenesis and may represent for a promising goal for therapeutic intervention following SAH (You et al, 2016 ; Zhang et al, 2016b ; Wu Q. et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage via Inhibition of NLRP3 Inflammasome Activation

Zhang

et al. 2017

Front. Neurosci.

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Previous studies have demonstrated resveratrol (RSV) has beneficial effects in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the beneficial effects of RSV and the underlying mechanisms have not been clearly identified. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays a crucial role in the EBI pathogenesis. The aim of this study was to investigate the role of RSV on the NLRP3 inflammasome signaling pathway and EBI in rats after SAH. A prechiasmatic cistern injection model was established in rats, and the primary cultured cortical neurons were stimulated with oxyhemoglobin (oxyHb) to induce SAH in vitro. It showed that the NLRP3 inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, mature interleukin-1β (IL-1β), and interleukin-18 (IL-18) were upregulated after SAH, and the enhanced NLRP3 after SAH was mainly located in microglia. Treatment with 60 or 90 mg/kg RSV after SAH dramatically inhibited the expression of NLRP3, but there was no significant difference in the expression of NLRP3 between the SAH + 60 mg/kg RSV and SAH + 90 mg/kg RSV groups. In addition, treatment with 30 mg/kg RSV did not significantly reduced the expression of NLRP3. We next evaluated the neuroprotective effects of RSV against SAH. We determined that SAH-induced NLRP3 inflammasome activation was significantly inhibited in the SAH + 60 mg/kg RSV group. Meanwhile, 60 mg/kg RSV administration could markedly inhibit microglia activation and neutrophils infiltration after SAH. Concomitant with the decreased cerebral inflammation, RSV evidently reduced cortical apoptosis, brain edema, and neurobehavioral impairment after SAH. In vitro experiments, RSV treatment also clearly protected primary cortical neurons against oxyHb insults, including reduced the proportion of neuronal apoptosis, alleviated neuronal degeneration, and improved cell viabilities. These in vitro data further confirm that RSV has an efficient neuroprotection against SAH. Taken together, these in vivo and in vitro findings suggested RSV could protect against EBI after SAH, at least partially via inhibiting NLRP3 inflammasome signaling pathway.

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Roflumilast Reduces Cerebral Inflammation in a Rat Model of Experimental Subarachnoid Hemorrhage

Cited by 34 publications

References 24 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

Resveratrol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage via Inhibition of NLRP3 Inflammasome Activation

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