Sildenafil Enhances Neurogenesis and Oligodendrogenesis in Ischemic Brain of Middle-Aged Mouse

Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia J.; Wei, Min; Wang, Xinli; Liu, Xianshuang; Lü, Mei; Zhang, Zheng Gang

doi:10.1371/journal.pone.0048141

Cited by 60 publications

(76 citation statements)

References 45 publications

(90 reference statements)

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“…69 Using a fate mapping strategy, studies demonstrate that stroke increases neural stem cell lineage OPCs and promotes these OPCs to differentiate into myelin forming oligodendrocytes in peri-infarct white matter. [49][50][51][52][53] These data suggest that OPCs generated by adult neural stem cells contribute to oligodendrogenesis after stroke.…”

Section: Perinatal H/i Injury and Stroke-induced Oligodendrogenesismentioning

confidence: 86%

Function of neural stem cells in ischemic brain repair processes

Zhang

Chopp

2016

J Cereb Blood Flow Metab

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Hypoxic/ischemic injury is the single most important cause of disabilities in infants, while stroke remains a leading cause of morbidity in children and adults around the world. The injured brain has limited repair capacity, and thereby only modest improvement of neurological function is evident post injury. In rodents, embryonic neural stem cells in the ventricular zone generate cortical neurons, and adult neural stem cells in the ventricular-subventricular zone of the lateral ventricle produce new neurons through animal life. In addition to generation of new neurons, neural stem cells contribute to oligodendrogenesis. Neurogenesis and oligodendrogenesis are essential for repair of injured brain. Much progress has been made in preclinical studies on elucidating the cellular and molecular mechanisms that control and coordinate neurogenesis and oligodendrogenesis in perinatal hypoxic/ischemic injury and the adult ischemic brain. This article will review these findings with a focus on the ventricular-subventricular zone neurogenic niche and discuss potential applications to facilitate endogenous neurogenesis and thereby to improve neurological function post perinatal hypoxic/ischemic injury and stroke.

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Section: Perinatal H/i Injury and Stroke-induced Oligodendrogenesismentioning

confidence: 86%

Function of neural stem cells in ischemic brain repair processes

Zhang

Chopp

2016

J Cereb Blood Flow Metab

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“…Mature oligodendrocytes are terminally differentiated and are vulnerable to cerebral ischemia. During brain repair processes, new oligodendrocytes generated by OPCs form myelin sheaths around the regenerated axons in periinfarct gray and white matter (48)(49)(50)(51). Recent studies indicate that cerebral endothelial cells actively and mutually interact with oligodendrocytes to facilitate angiogenesis and oligodendrogenesis during repair after stroke (52).…”

Section: Exosomes and Cerebral Angiogenesismentioning

confidence: 99%

Exosomes in stroke pathogenesis and therapy

Zhang¹,

Chopp²

2016

Journal of Clinical Investigation

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“…For instance, the elevation of cGMP by sildenafil (10 mg/kg) enhances neurogenesis, angiogenesis, and synaptic plasticity, closely associated with improvements in neurological outcome and memory in animal models of adult stroke 30,31 and Alzheimer's disease. 32 Recently, Zhang et al 33 have also demonstrated that sildenafil enhances nestin expression in neural stem cells and the generation of neuronal and oligodendroglial progeny in the ischemic brain of the middle-aged mouse. Whether sildenafil could induce similar changes in the developing brain remains to be elucidated.…”

Section: March 2014mentioning

confidence: 99%

Sildenafil Mediates Blood-Flow Redistribution and Neuroprotection After Neonatal Hypoxia-Ischemia

Charriaut‐Marlangue

Nguyen

Bonnin

et al. 2014

Stroke

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The goal of this study was to test the hypothesis that boosting NO-cGMP signaling through PDE-5 inhibition with sildenafil would enhance microcirculatory CBF, reduce ipsilateral Background and Purpose-The best conceivable treatment for hypoxia-ischemia (HI) is the restoration of blood flow to the hypoxic-ischemic region(s). Our objective was to examine whether boosting NO-cGMP signaling using sildenafil citrate, a phosphodiesterase-type 5 inhibitor, could modify cerebral blood flow and reduce lesions in the developing brain. Methods-HI was induced in P7 Sprague-Dawley rats by unilateral carotid artery occlusion and hypoxia, and followed by either PBS or sildenafil. Blood-flow velocities were measured by ultrasound imaging with sequential Doppler recordings to evaluate collateral recruitment. Cell death, blood-brain barrier integrity, and glial activation were analyzed by immunohistochemistry. Motor behavior was evaluated using an open-field device adapted to neonatal animals. Results-Sildenafil citrate (10 mg/kg) induced collateral patency, reduced terminal dUTP nick-end labeling-positive cells, reactive astrogliosis, and macrophage/microglial activation at 72 hours and 7 days post-HI. Sildenafil also reduced the number of terminal dUTP nick-end labeling-positive endothelial cells within lesion site. Seven days after HI and sildenafil treatment, tissue loss was significantly reduced, and animals recovered motor coordination. Conclusions-Our findings strongly indicate that sildenafil citrate treatment, associated with a significant increase in cerebral blood flow, reduces HI damage and improves motor locomotion in neonatal rats. Sildenafil may represent an interesting therapeutic strategy for neonatal neuroprotection.

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Sildenafil Enhances Neurogenesis and Oligodendrogenesis in Ischemic Brain of Middle-Aged Mouse

Cited by 60 publications

References 45 publications

Function of neural stem cells in ischemic brain repair processes

Function of neural stem cells in ischemic brain repair processes

Exosomes in stroke pathogenesis and therapy

Sildenafil Mediates Blood-Flow Redistribution and Neuroprotection After Neonatal Hypoxia-Ischemia

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