Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

Wang, Yan; Bao, Dejun; Xu, Bin; Chen, Cheng; Dong, Yongfei; Wei, Xiangpin; Niu, Chaoshi

doi:10.4103/1673-5374.250620

Cited by 19 publications

(12 citation statements)

References 52 publications

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“…On the other hand, the exogenous delivery of recombinant human Wnt1 (rhWnt1) into the ventricle of SAH rats decreased brain edema and ameliorated neurological functions (Wang Y. et al, 2019). Interestingly, these beneficial effects were totally abolished after administration of Wnt1 siRNA or a neutralizing monoclonal antibody anti-Fzd1 (Wang Y. et al, 2019). These results highlight the importance of the canonical Wnt pathway as a therapeutic target to promote neurovascular repair following hemorrhagic stroke.…”

Section: Implication In Hemorrhagic Stroke Therapymentioning

confidence: 94%

“…On the other hand, Dkk1 expression in the basal ganglia and peri-hematomal remarkably increased during early brain injury associated to ICH, whereas it remains unchanged in the contralateral basal ganglia and in the blood serum (Li Z. et al, 2017;Wang G. et al, 2019). Interestingly, Dkk1 expression was found in the neuron and microglia but not in astrocytes (Wang G. et al, 2019), and correlated with a decreased level of Wnt1 in neurons (Wang Y. et al, 2019). GSK3β was activated as well in early brain injury as well as in the second phase of hemorrhagic stroke within the CA1, CA3, and DG regions of the hippocampus (Liu et al, 2018).…”

Section: Implication In Hemorrhagic Stroke Pathobiologymentioning

confidence: 99%

“…Aldolase C, a positive regulator of Wnt signaling that acts through destabilization of Axin, significantly increased during early brain injury associated to SAH, subsequently increasing the expression of Axin (Ruan et al, 2020). Following SAH, Wnt1 and Wnt3a levels significantly decreased 12 h after onset (Wang Y. et al, 2019;Ruan et al, 2020), whereas the levels of β-catenin, Fzd1 decreased as early as 6 h after onset (Wang Y. et al, 2019;Ruan et al, 2020). Twenty-four hours after ICH and SAH, the ratio of p-tyrosine-GSK3β/GSK3β (i.e., indicating an enhanced kinase activity) (Krafft et al, 2012(Krafft et al, , 2013Zuo et al, 2017), and p-serine-βcatenin/β-catenin were increased (Krafft et al, 2013;Zuo et al, 2017;, whereas the ratio p-serine-GSK3β/GSK3β (i.e., indicating a reduced kinase activity) was decreased .…”

Section: Implication In Hemorrhagic Stroke Pathobiologymentioning

confidence: 99%

“…Administration of the Wnt inhibitor XAV939 counteracted most of the beneficial effect of Wnt3a after SAH (Ruan et al, 2020). On the other hand, the exogenous delivery of recombinant human Wnt1 (rhWnt1) into the ventricle of SAH rats decreased brain edema and ameliorated neurological functions (Wang Y. et al, 2019). Interestingly, these beneficial effects were totally abolished after administration of Wnt1 siRNA or a neutralizing monoclonal antibody anti-Fzd1 (Wang Y. et al, 2019).…”

Section: Implication In Hemorrhagic Stroke Therapymentioning

confidence: 99%

“…M1type microglia promote the inflammatory response by releasing pro-inflammatory mediators, such as TNFα, IL1β, and IL6, exacerbating tissue damage (Ueba et al, 2018), whereas M2-type microglia exert protective effects by promoting the release of antiinflammatory mediators and trophic factors, and contribute to tissue repair (Yang et al, 2018). Increasing the brain levels of Wnt1 via the delivery of rhWnt1 alleviated early brain injury associated to SAH in rats, which was accompanied by increased expression of β-catenin (Wang Y. et al, 2019). Activation of the canonical Wnt pathway via rhWnt1 delivery stimulated microglia cell polarization toward a M2-type reparative phenotype during the early brain injury phase by increasing the expression of CD36, CD206 and peroxisome proliferator-activated receptor-γ (PPARγ), and decreasing the protein levels of NF-κB (Wang Y. et al, 2019).…”

Section: Implication In Hemorrhagic Stroke Therapymentioning

confidence: 99%

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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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Section: Implication In Hemorrhagic Stroke Therapymentioning

confidence: 94%

Section: Implication In Hemorrhagic Stroke Pathobiologymentioning

confidence: 99%

Section: Implication In Hemorrhagic Stroke Pathobiologymentioning

confidence: 99%

Section: Implication In Hemorrhagic Stroke Therapymentioning

confidence: 99%

Section: Implication In Hemorrhagic Stroke Therapymentioning

confidence: 99%

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

2020

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Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord

González

González-Fernández

Campos-Martín

et al. 2020

Cell. Mol. Life Sci.

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Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats

Yu,

Huang,

Zhao

et al. 2023

Mol Neurobiol

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Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in the central nervous system and are profoundly involved in neuroinflammation. Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear. This study aimed to clarify the effect and mechanism of atorvastatin on the regulation of microglia function in neonatal hypoxic-ischemic brain damage (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD model was established. Atorvastatin, recombinant sclerostin protein (SOST), and XAV939 (degradation of β-catenin) were administered to OGD microglia and HIBD rats. The pathological changes of brain tissue, cerebral infarction volume, learning and memory ability of rats, pro-inflammatory (CD16+/Iba1+) and anti-inflammatory (CD206+/Iba1+) microglia markers, inflammation-related indicators (Inos, Tnfα, Il6, Arg1, Tgfb, and Mrc1), and Wnt/β-catenin signaling molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory microglia and pro-inflammatory factors, while increasing anti-inflammatory microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. Mechanistically, atorvastatin decreased SOST expression and activated the Wnt/β-catenin signaling pathway, and the administration of recombinant SOST protein or XAV939 inhibited Wnt/β-catenin signaling and attenuated the anti-inflammatory effect of atorvastatin. Atorvastatin promotes the pro/anti-inflammatory phenotypic transformation of microglia via the Wnt/β-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a potent agent for the treatment of HIE in neonates.

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Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage

Cited by 19 publications

References 52 publications

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

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

Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord

Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats

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