Alterations in hippocampal neurogenesis following traumatic brain injury in mice

Rola, Radosław; Mizumatsu, Shinichiro; Otsuka, Shinji; Morhardt, Duncan R.; Noble-Haeusslein, Linda J.; Fishman, Kelly; Potts, Matthew B.; Fike, John R.

doi:10.1016/j.expneurol.2006.05.034

Cited by 156 publications

(169 citation statements)

References 68 publications

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“…This is consistent with the findings of some studies [61,62], although in others, an increase in progenitors and neurogenesis has been reported [29,39,63,64]. Interestingly, similar to our PSA-NCAM1 population results, a study by Yu et al [65] reported a loss of intermediate (Dcx1) progenitors early after injury in mice, which recovered over several days; however, the percentage of new intermediates (Dcx1/BrdU1) at 7 days was increased, dissimilar to our observations.…”

Section: Discussionsupporting

confidence: 91%

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

2013

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The p75 neurotrophin receptor (p75 NTR ) influences the proliferation, survival, and differentiation of neuronal precursors and its expression is induced in injured brain, where it regulates cell survival. Here, we test the hypotheses that pharmacologic modulation of p75 NTR signaling will promote neural progenitor survival and proliferation, and improve outcomes of traumatic brain injury (TBI). LM11A-31, an orally available, blood-brain barrier-permeant small-molecule p75 NTR signaling modulator, significantly increased proliferation and survival, and decreased JNK phosphorylation, in hippocampal neural stem/progenitor cells in culture expressing wild-type p75 NTR , but had no effect on cells expressing a mutant neurotrophinunresponsive form of the receptor. The compound also enhanced the production of mature neurons from adult hippocampal neural progenitors in vitro. In vivo, intranasal administration of LM11A-31 decreased postinjury hippocampal and cortical neuronal death, neural progenitor cell death, gliogenesis, and microglial activation, and enhanced long-term hippocampal neurogenesis and reversed spatial memory impairments. LM11A-31 diminished the postinjury increase of SOX2-expressing early progenitor cells, but protected and increased the proliferation of endogenous polysialylated-neural cell adhesion molecule positive intermediate progenitors, and restored the long-term production of mature granule neurons. These findings suggest that modulation of p75 NTR actions using small molecules such as LM11A-31 may constitute a potent therapeutic strategy for TBI. STEM CELLS

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Section: Discussionsupporting

confidence: 91%

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

2013

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“…Although TBI activates and stimulates type-I quiescent progenitor cells to proliferate, it also eliminates DCX-expressing late progenitor cells in the DG (Yu et al, 2008). Here we show a significant reduction in neurogenesis and immature neurons in the brain-injured ipsilateral DG, consistent with a previous report (Rola et al, 2006). Thus, despite the proliferation of type I progenitor cells, the local environment in the DG may not be favorable to the survival of newborn neurons, thus causing a net decrease in the total DCX population in the long run.…”

Section: Figsupporting

confidence: 93%

Fluoxetine Increases Hippocampal Neurogenesis and Induces Epigenetic Factors But Does Not Improve Functional Recovery after Traumatic Brain Injury

Wang

Neumann

Hansen

et al. 2011

Journal of Neurotrauma

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The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalkassisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine-and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits.

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“…Alternatively, if MTP functions as a defensive molecule, a defect in MTP expression might not exhibit a significant consequence in brain function unless challenged by injury or stress. Our newest data shows that NP cells lacking MTP are more sensitive to injury-induced cell death, 6 which appears to support the role of MTP in cellular defense.…”

Section: Discussionsupporting

confidence: 62%

“…In the normal brain, constitutive neurogenesis is found in two locations: the subventricular zone (SVZ) 2 of the lateral ventricle (LV), which gives rise to interneurons in the olfactory bulb, and the dentate gyrus subgranular zone of the hippocampus (HP), which gives rise to neurons in the dentate granule cell circuitry for memory and learning (1,2). It has been shown that proliferation of neural progenitor (NP) cells in both locations is enhanced after brain injuries, and streams of neuroblasts are attracted by and move toward the injured sites (3)(4)(5)(6)(7). However, there is not significant endogeneous neurogenesis to regenerate the damaged areas (8,9).…”

mentioning

confidence: 99%

Endogenous Expression of Matriptase in Neural Progenitor Cells Promotes Cell Migration and Neuron Differentiation

Fang

Chou

Tung

et al. 2011

Journal of Biological Chemistry

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Recent studies show that type II transmembrane serine proteases play important roles in diverse cellular activities and pathological processes. Their expression and functions in the central nervous system, however, are largely unexplored. In this study, we show that the expression of one such member, matriptase (MTP), was cell type-restricted and primarily expressed in neural progenitor (NP) cells and neurons. Blocking MTP expression or MTP activity prevented NP cell traverse of reconstituted basement membrane, whereas overexpression of MTP promoted it. The NP cell mobilization induced by either vascular endothelial growth factor or hepatocyte growth factor was also impaired by knocking down MTP expression. MTP acts upstream of matrix metalloproteinase 2 in promoting NP cell mobility. In embryonic stem cell differentiation to neural cells, MTP knockdown had no effect on entry of embryonic stem cells into the neural lineage. High MTP expression or activity, however, shifts the population dynamics from NP cells toward neurons to favor neuronal differentiation. This is the first report to demonstrate the direct involvement of type II transmembrane serine protease in NP cell function.

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Alterations in hippocampal neurogenesis following traumatic brain injury in mice

Cited by 156 publications

References 68 publications

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

A small molecule p75NTR ligand protects neurogenesis after traumatic brain injury

Fluoxetine Increases Hippocampal Neurogenesis and Induces Epigenetic Factors But Does Not Improve Functional Recovery after Traumatic Brain Injury

Endogenous Expression of Matriptase in Neural Progenitor Cells Promotes Cell Migration and Neuron Differentiation

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