Increased ICP promotes CaMKII-mediated phosphorylation of neuronal NOS at Ser847 in the hippocampus immediately after subarachnoid hemorrhage

Stroke is considered to be an acute cerebrovascular disease, including ischemic stroke and hemorrhagic stroke. The high incidence and poor prognosis of stroke suggest that it is a highly disabling and highly lethal disease which can pose a serious threat to human health. Nitric oxide (NO), a common gas in nature, which is often thought as a toxic gas, because of its intimate relationship with the pathological processes of many diseases, especially in the regulation of blood flow and cell inflammation. However, recent years have witnessed an increased interest that NO plays a significant and positive role in stroke as an essential gas signal molecule. In view of the fact that the neuroprotective effect of NO is closely related to its concentration, cell type and time, only in the appropriate circumstances can NO play a protective effect. The purpose of this review is to summarize the roles of NO in ischemic stroke and hemorrhagic stroke.

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“…The phosphorylation of nNOS reduces ischemic injury and plays a neuroprotective effect in early brain injury. 69 …”

Section: Echanisms Of No In Smentioning

confidence: 99%

The role of nitric oxide in stroke

et al. 2017

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“…It has been reported that NP847 can inhibit the negative regulation of nNOS during neurogenesis by decreasing the activity of nNOS (Osuka et al, 2007). Makino et al reported that the activation of NP847 in the hippocampus alleviates ischemic insults immediately after SAH to exert a neuroprotective effect (Makino et al, 2015). Moreover, protein phosphatase 2A (PP2A) can dephosphorylate the Ser847 residue of NP847 to recover nNOS enzymatic activity (Komeima et al, 2000; Komeima and Watanabe, 2001).…”

Section: Discussionmentioning

confidence: 99%

The Expression of NP847 and Sox2 after TBI and Its Influence on NSCs

Bao

Chen

et al. 2016

Front. Cell. Neurosci.

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The proliferation and differentiation of neural stem cells (NSCs) is important for neural regeneration after cerebral injury. Here, for the first time, we show that phosphorylated (p)-ser847-nNOS (NP847), rather than nNOS, may play a major role in NSC proliferation after traumatic brain injury (TBI). Western blot results demonstrated that the expression of NP847 and Sox2 in the hippocampus is up-regulated after TBI, and they both peak 3 days after brain injury. In addition, an immunofluorescence experiment indicated that NP847 and Sox2 partly co-localize in the nuclei of NSCs after TBI. Further immunoprecipitation experiments found that NP847 and Sox2 can directly interact with each other in NSCs. Moreover, in an OGD model of NSCs, NP847 expression is decreased, which is followed by the down-regulation of Sox2. Interestingly, in this study, we did not observe changes in the expression of nNOS in the OGD model. Further research data suggest that the NP847-Sox2 complex may play a major role in NSCs through the Shh/Gli signaling pathway in a CaMKII-dependent manner after brain injury.

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“…CaMKIIα, which is one of the major isoforms of CaMKII, was shown to modulate the inflammatory response of microglial cells (Huang et al, 2015). Tyrosine phosphorylation of CaMKIIα, which modulate protein kinase activity, was shown to increase immediately after SAH induction essentially in neurons and microglia within the lesion site (Makino et al, 2015;Zhou et al, 2018) (Figure 2).…”

Section: Implication In Hemorrhagic Stroke Pathobiologymentioning

confidence: 99%

Wnt Pathway: An Emerging Player in Vascular and Traumatic Mediated Brain Injuries

2020

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The Wnt pathway, which comprises the canonical and non-canonical pathways, is an evolutionarily conserved mechanism that regulates crucial biological aspects throughout the development and adulthood. Emergence and patterning of the nervous and vascular systems are intimately coordinated, a process in which Wnt pathway plays particularly important roles. In the brain, Wnt ligands activate a cellspecific surface receptor complex to induce intracellular signaling cascades regulating neurogenesis, synaptogenesis, neuronal plasticity, synaptic plasticity, angiogenesis, vascular stabilization, and inflammation. The Wnt pathway is tightly regulated in the adult brain to maintain neurovascular functions. Historically, research in neuroscience has emphasized essentially on investigating the pathway in neurodegenerative disorders. Nonetheless, emerging findings have demonstrated that the pathway is deregulated in vascular-and traumatic-mediated brain injuries. These findings are suggesting that the pathway constitutes a promising target for the development of novel therapeutic protective and restorative interventions. Yet, targeting a complex multifunctional signal transduction pathway remains a major challenge. The review aims to summarize the current knowledge regarding the implication of Wnt pathway in the pathobiology of ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI). Furthermore, the review will present the strategies used so far to manipulate the pathway for therapeutic purposes as to highlight potential future directions.

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Increased ICP promotes CaMKII-mediated phosphorylation of neuronal NOS at Ser847 in the hippocampus immediately after subarachnoid hemorrhage

Cited by 11 publications

References 37 publications

The role of nitric oxide in stroke

The role of nitric oxide in stroke

The Expression of NP847 and Sox2 after TBI and Its Influence on NSCs

Wnt Pathway: An Emerging Player in Vascular and Traumatic Mediated Brain Injuries

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