RIP1-RIP3-DRP1 pathway regulates NLRP3 inflammasome activation following subarachnoid hemorrhage.

In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection. SAH grade, neurological function, brain water content, Western blot, ROS assay, immunofluorescence and transmission electron microscopy were performed. SAH led to the upregulation of RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome. Nec-1 treatment reduced RIP1, RIP3, phosphorylated DRP1 and NLRP3 inflammasome, subsequently alleviated brain edema and neurological deficits at 24h following SAH. The treatment with Mdivi-1 inhibited the expression of DRP1 protein, attenuated mitochondria damage and the generation of ROS, inhibition NLRP3 inflammasome and ameliorated brain edema and neurological deficits at 24h after SAH. The activation of the NLRP3 inflammasome in EBI after SAH was mediated by RIP1-RIP3-DRP1 pathway. Nec-1 and Mdivi-1 can inhibit inflammation and improve neurological function after SAH. PMID: 28579326 [PubMed - as supplied by publisher]
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

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Authors: Chen H, Dang Y, Liu X, Ren J, Wang H Abstract Brain-derived neurotrophic factor (BDNF) is a growth factor crucial for neuronal survival, while its role in subarachnoid hemorrhage (SAH)-induced neuronal apoptosis remains unclear. The aim of the present study was to investigate whether administering exogenous BDNF can protect against neuronal apoptosis and neurological deficits following SAH in a rat model. The BDNF level was found to be significantly decreased in the basal cortex at 6, 12, 24, 48 and 72 h following SAH. Exogenous BDNF significantly decreased the expression of Bax and reduced activation of c...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
In this study, we investigated the dynamics of microglial reaction in an endovascular perforated SAH model. By using the Cx3cr1GFP/GFP Ccr2RFP/RFP transgenic mice, we found that the reactive immune cells were largely from resident microglia pool rather than infiltrating macrophages. Immunostaining and real-time PCR were employed to analyze the temporal microglial polarization and the resulting inflammatory responses. Our results showed that microglia accumulated immediately after SAH with a centrifugal spreading through the Cortex Adjacent to the Perforated Site (CAPS) to the remote motor cortex. Microglia polarized dynami...
Source: Translational Stroke Research - Category: Neurology Source Type: research
ConclusionsSerum soluble LOX-1 appears to have the potential to become a promising prognostic predictor after human aneurysmal SAH.
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
In this study, we show that glycine can reduce brain edema and protect neurons in SAH via a novel pathway. Following a hemorrhagic episode, there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), and this can be reversed with glycine treatment. We also found that administration of glycine can reduce neuronal cell death in SAH by activating the AKT pathway. Glycine was shown to upregulate miRNA-26b, which led to PTEN downregulation followed by AKT activation, resulting in inhibition of neuronal death. Inhibition of miRNA-26b, PTEN or AKT activation suppressed the neuroprotective effects of glycine. Glyci...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
Conclusion: The ipsilateral ONP is a common sign found in posterior communicating artery aneurysms; however, such aneurysm can have different presentations due to the elevation of intracranial pressure, and, in rarer cases, the ONP cannot be operated as a localizing sign. PMID: 31583174 [PubMed]
Source: Surgical Neurology International - Category: Neurosurgery Tags: Surg Neurol Int Source Type: research
Background: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI.
Source: Journal of Stroke and Cerebrovascular Diseases - Category: Neurology Authors: Source Type: research
ConclusionSimple clinical features could help distinguish cSAH-associated TFNE from suspected TIA, with relevance for investigation and management, including the use of antithrombotic drugs.
Source: Journal of Neurology - Category: Neurology Source Type: research
Conclusion: Asian neuroscientists published enormous contributions in SAH-related autonomic nervous system dysfunction. It was shown that there is a great interest of Asian neuroscientists for autonomic nervous system changes secondary to SAH.
Source: Journal of Craniofacial Surgery - Category: Surgery Tags: Clinical Studies Source Type: research
CONCLUSIONS: Subarachnoid hemorrhage causes very early BBB disruption and LCN2 expression in white matter that is associated with and may precede T2 hyperintensities. LCN2 deletion attenuates MRI changes and pathological changes in white matter after SAH. PMID: 31568658 [PubMed - as supplied by publisher]
Source: CNS Neuroscience and Therapeutics - Category: Neuroscience Authors: Tags: CNS Neurosci Ther Source Type: research
CW Abstract Nimodipine is a dihydropyridine calcium channel antagonist that blocks the flux of extracellular calcium through L-type, voltage-gated calcium channels. While nimodipine is FDA-approved for the prevention and treatment of neurological deficits in patients with aneurysmal subarachnoid hemorrhage (aSAH), it affects myriad cell types throughout the body, and thus, likely has more complex mechanisms of action than simple inhibition of cerebral vasoconstriction. Newer understanding of the pathophysiology of delayed ischemic injury after a variety of acute neurologic injuries including aSAH, traumatic brain...
Source: Current Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Neuropharmacol Source Type: research
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