Exercise Training Inhibits the Nogo-A/NgR1/Rho-A Signals in the Cortical Peri-infarct Area in Hypertensive Stroke Rats

Li, Chao; Wen, Hongmei; Wang, QingMei; Zhang, Chanjuan; Jiang, Li; Dou, Zulin; Luo, Xun

doi:10.1097/phm.0000000000000339

Cited by 17 publications

(14 citation statements)

References 66 publications

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“…Nogo-A, as the pivotal myelin-associated axonal growth inhibitory protein, is a major impediment to axonal regeneration following ischemic stroke (26). Previous studies have shown that downregulation or inhibition of the Nogo-A signaling pathway promoted axonal regeneration and functional recovery of stroke (27–29). Nogo-A, via the NgR complex, activates RhoA and ROCK, ultimately resulting in the inhibition of axonal regeneration and growth cone collapse (15).…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture promotes axonal regeneration in rats with focal cerebral ischemia through the downregulation of Nogo-A/NgR/RhoA/ROCK signaling

Huang

Huang²,

Zhao

et al. 2017

Experimental and Therapeutic Medicine

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The purpose of the present study was to evaluate the effect of electroacupuncture (EA) on the axonal regeneration environment following cerebral ischemia injury and to investigate whether it was associated with Nogo-A/Nogo receptor (NgR)/RhoA/Rho-associated protein kinase (ROCK) signaling. Using a rat model of focal cerebral ischemia, the effects of EA at the Quchi (LI11) and Zusanli (ST36) acupoints on axonal growth inhibitory protein and axonal growth factors were assessed and the underlying molecular mechanisms were investigated. It was found that EA at the Quchi and Zusanli acupoints significantly improved neurological deficit scores following ischemia (P<0.05), and reduced the cerebral infarct volume. Moreover, it was demonstrated that crucial signaling molecules in the Nogo-A signaling pathway were regulated by EA. These results suggest that EA provides a less inhibitory environment for axonal regeneration following cerebral ischemia through inhibition of Nogo-A/NgR/RhoA/ROCK signaling.

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Section: Discussionmentioning

confidence: 99%

Electroacupuncture promotes axonal regeneration in rats with focal cerebral ischemia through the downregulation of Nogo-A/NgR/RhoA/ROCK signaling

Huang

Huang²,

Zhao

et al. 2017

Experimental and Therapeutic Medicine

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“…Five successive coronal sections at 2.0 mm intervals from Bregma +4.0 to −6.0 mm were selected for quantification of the infarct volume. The volumes of the ipsilateral and the contralateral hemisphere were quantified as previously described [42,43] and the relative infarct volume was expressed as a percentage of the total volume of the contralateral hemisphere. Nissl staining was performed with 0.1% cresyl violet (Sigma-Aldrich, St. Louis, MO, USA) according to the standard procedure.…”

Section: Methodsmentioning

confidence: 99%

High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

Luo

Zheng

Zhang

et al. 2017

IJMS

110

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Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO), following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX), NeuN and glial fibrillary acidic protein (GFAP), and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.

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“…Following MCAo the change in synaptic density and structure following 2 weeks of EE has also been associated with improved functional recovery on a spatial memory task (Xu et al, 2009 ). Further, both exercise and EE enhance axonal sprouting and reduce white matter damage (Papadopoulos et al, 2009 ; Li et al, 2015 ; Hase et al, 2017 , 2018 ). Running wheel exercise, often included in EE paradigms and associated with improved functional recovery, enhances axonal remodeling following focal cortical stroke (Li et al, 2015 ).…”

Section: How Does Enrichment Enhance Plasticity and Recovery From Strmentioning

confidence: 99%

Is Environmental Enrichment Ready for Clinical Application in Human Post-stroke Rehabilitation?

McDonald

Hayward

Rosbergen

et al. 2018

Front. Behav. Neurosci.

109

104

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Environmental enrichment (EE) has been widely used as a means to enhance brain plasticity mechanisms (e.g., increased dendritic branching, synaptogenesis, etc.) and improve behavioral function in both normal and brain-damaged animals. In spite of the demonstrated efficacy of EE for enhancing brain plasticity, it has largely remained a laboratory phenomenon with little translation to the clinical setting. Impediments to the implementation of enrichment as an intervention for human stroke rehabilitation and a lack of clinical translation can be attributed to a number of factors not limited to: (i) concerns that EE is actually the “normal state” for animals, whereas standard housing is a form of impoverishment; (ii) difficulty in standardizing EE conditions across clinical sites; (iii) the exact mechanisms underlying the beneficial actions of enrichment are largely correlative in nature; (iv) a lack of knowledge concerning what aspects of enrichment (e.g., exercise, socialization, cognitive stimulation) represent the critical or active ingredients for enhancing brain plasticity; and (v) the required “dose” of enrichment is unknown, since most laboratory studies employ continuous periods of enrichment, a condition that most clinicians view as impractical. In this review article, we summarize preclinical stroke recovery studies that have successfully utilized EE to promote functional recovery and highlight the potential underlying mechanisms. Subsequently, we discuss how EE is being applied in a clinical setting and address differences in preclinical and clinical EE work to date. It is argued that the best way forward is through the careful alignment of preclinical and clinical rehabilitation research. A combination of both approaches will allow research to fully address gaps in knowledge and facilitate the implementation of EE to the clinical setting.

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Exercise Training Inhibits the Nogo-A/NgR1/Rho-A Signals in the Cortical Peri-infarct Area in Hypertensive Stroke Rats

Abstract: Exercise training promotes axonal recovery, which is associated with functional improvement after cerebral infarction. Down-regulation of the Nogo-A/NgR1/Rho-A may mediate the axonal remodeling induced by exercise training.

Cited by 17 publications

References 66 publications

Electroacupuncture promotes axonal regeneration in rats with focal cerebral ischemia through the downregulation of Nogo-A/NgR/RhoA/ROCK signaling

Electroacupuncture promotes axonal regeneration in rats with focal cerebral ischemia through the downregulation of Nogo-A/NgR/RhoA/ROCK signaling

High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

Is Environmental Enrichment Ready for Clinical Application in Human Post-stroke Rehabilitation?

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