Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury

Lu, Paul; Jones, Leonard L.; Snyder, E.; Tuszynski, Mark H.

doi:10.1016/s0014-4886(03)00037-2

Cited by 790 publications

(599 citation statements)

References 42 publications

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“…Moreover, antibodies directed against BDNF and SCF blocked the NSI‐189‐mediated rescue of cell viability against OGD. Similar reports have demonstrated cross‐talk between secreted factors (e.g., apoptosis, inflammation, oxidative stress) (; Brill et al, 2009; Chapman et al, 2015; Lu, Jones, Snyder, & Tuszynski, 2003; Zhang et al, 2015) and neurogenesis following brain insults, including stroke (Kernie and Parent, 2010; Yamashita et al, 2006). We (Hara et al, 2007; Morimoto et al, 2011; Tajiri et al, 2013), and others, have shown the important contribution of neurogenic factors in stroke brain remodeling (Jablonska et al, 2016; Rosell et al, 2013; Seo et al, 2014; Venna, Xu, Doran, Patrizz, & McCullough, 2014).…”

Section: Discussionmentioning

confidence: 56%

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

Tajiri

Quach

Kaneko

et al. 2017

Journal Cellular Physiology

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Enhancing neurogenesis may be a powerful stroke therapy. Here, we tested in a rat model of ischemic stroke the beneficial effects of NSI‐189, an orally active, new molecular entity (mol. wt. 366) with enhanced neurogenic activity, and indicated as an anti‐depressant drug in a clinical trial (Fava et al., 2015, Molecular Psychiatry, DOI: 10.1038/mp.2015.178) and being tested in a Phase 2 efficacy trial (ClinicalTrials.gov, 2016, ClinicalTrials.gov Identifier: NCT02695472) for treatment of major depression. Oral administration of NSI‐189 in adult Sprague–Dawley rats starting at 6 hr after middle cerebral artery occlusion, and daily thereafter over the next 12 weeks resulted in significant amelioration of stroke‐induced motor and neurological deficits, which was maintained up to 24 weeks post‐stroke. Histopathological assessment of stroke brains from NSI‐189‐treated animals revealed significant increments in neurite outgrowth as evidenced by MAP2 immunoreactivity that was prominently detected in the hippocampus and partially in the cortex. These results suggest NSI‐189 actively stimulated remodeling of the stroke brain. Parallel in vitro studies further probed this remodeling process and demonstrated that oxygen glucose deprivation and reperfusion (OGD/R) initiated typical cell death processes, which were reversed by NSI‐189 treatment characterized by significant attenuation of OGD/R‐mediated hippocampal cell death and increased Ki67 and MAP2 expression, coupled with upregulation of neurogenic factors such as BDNF and SCF. These findings support the use of oral NSI‐189 as a therapeutic agent well beyond the initial 6‐hr time window to accelerate and enhance the overall functional improvement in the initial 6 months post stroke.

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Section: Discussionmentioning

confidence: 56%

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

Tajiri

Quach

Kaneko

et al. 2017

Journal Cellular Physiology

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“…The mechanism by which neural progenitors might induce such an effect is not known. One possibility is the induction of cytokines by neural progenitors, [8][9][10] which enhance proliferation of endogenous neural cells. [11][12][13][14][15] Here, we aimed to examine our hypothesis by employing the prenatally heroin-damaged brain model.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

2007

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Grafting of neural progenitors has been shown to reverse a wide variety of neurobehavioral defects. While their role of replacing injured cells and restoring damaged circuitries has been shown, it is widely accepted that this cannot be the only mechanism, as therapy can occur even when an insufficient number of transplanted cells are found. We hypothesized that one major mechanism by which transplanted neural progenitors exert their therapeutic effect is by enhancing endogenous cells production. Consequently, in an allographic model of transplantation, prenatally heroin-exposed genetically heterogeneous (HS) mice were made defective in their hippocampal neurobehavioral function by exposing their mothers to heroin (10 mg kg À1 heroin on gestation days 9-18). Hippocampal damage was confirmed by deficient performance in the Morris maze (P < 0.009), and decreased production of endogenous cells in the dentate gyrus by 39% was observed. On postnatal day 35, they received an HS-derived neural progenitors transplant followed by repeated bromodeoxyuridine injections. The transplant returned endogenous cells production to normal levels (P < 0.006) and reversed the behavioral defects (P < 0.03), despite the fact that only 0.0334% of the transplanted neural progenitors survived and that they differentiated mainly to astrocytes. An immunological study demonstrated the presence of macrophages and T cells as a possible explanation for the paucity of the transplanted cells. This study suggests one mechanism for the therapeutic action of neural progenitors, the enhancement of the production of endogenous cells, pointing to future clinical applications in this direction by use of neural progenitors or by analogous cell-inducing techniques.

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“…139 Stem cells may present a cellular substrate at the lesion site to support axonal extension. In addition, stem cells may not require a prolonged presence to function; their mechanism of action may be through growth factor expression (BDNF, NGF and neurotrophin-3), 140 inhibition of demyelination and as an initial lattice of cellular substrate.…”

Section: Escsmentioning

confidence: 99%

Stem cells: novel players in the treatment of erectile dysfunction

Zhang¹,

Albersen²,

Jin³

et al. 2011

Asian J Androl

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Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury

Cited by 790 publications

References 42 publications

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

Stem cells: novel players in the treatment of erectile dysfunction

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