Neurogenesis in Adult Human Brain after Traumatic Brain Injury

First Affiliated Hospital, Wenzhou Medical College, Department of Neurosurgery, Wenzhou, China
Journal of neurotrauma (Impact Factor: 3.71). 01/2011; 30(22). DOI: 10.1089/neu.2010.1579
Source: PubMed


While much work has been conducted regarding the neurogenesis response to traumatic brain injury (TBI) in rodents, it remains largely unknown whether neurogenesis in adult human brain also responds to TBI in a similar manner. Here, we performed immunocytochemistry on eleven brain specimens from patients with traumatic brain injury, who underwent surgical intervention. We found that expression of neural stem/progenitor cell (NSC) protein markers including DCX, TUC4, PSA-NCAM, SOX2 and NeuroD were increased in the perilesional cortex of human brain after TBI, compared to normal brain. Confocal images showed that these NSC proteins were expressed in one single cell. We also found that proliferative markers were expressed in NSC protein-positive cells after TBI, and the number of proliferative NSCs was significantly increased after TBI. Our data suggest that TBI may also induce neurogenesis in human brain.

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    • "Continuous generation of new neurons from neural stem/progenitor cells in the subgranular zone of the DG is essential for hippocampus-dependent learning and memory [81]. Increased neurogenesis occurs in the hippocampus of adult animals and humans after TBI, which may contribute to spontaneous hippocampus-dependent functional recovery [6], [82], [83]. Preclinical data from us and others have shown that a large proportion of newly generated cells in the DG die within one month in rodents after TBI [82], [84]. "
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    ABSTRACT: Traumatic brain injury (TBI) is a major cause of death and long-term disability worldwide. To date, there are no effective pharmacological treatments for TBI. Recombinant human tissue plasminogen activator (tPA) is the effective drug for the treatment of acute ischemic stroke. In addition to its thrombolytic effect, tPA is also involved in neuroplasticity in the central nervous system. However, tPA has potential adverse side effects when administered intravenously including brain edema and hemorrhage. Here we report that tPA, administered by intranasal delivery during the subacute phase after TBI, provides therapeutic benefit. Animals with TBI were treated intranasally with saline or tPA initiated 7 days after TBI. Compared with saline treatment, subacute intranasal tPA treatment significantly 1) improved cognitive (Morris water maze test) and sensorimotor (footfault and modified neurological severity score) functional recovery in rats after TBI, 2) reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, 3) enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and 4) increased the level of mature brain-derived neurotrophic factor. Our data suggest that subacute intranasal tPA treatment improves functional recovery and promotes brain neurogenesis and spinal cord axonal sprouting after TBI, which may be mediated, at least in part, by tPA/plasmin-dependent maturation of brain-derived neurotrophic factor.
    PLoS ONE 09/2014; 9(9):e106238. DOI:10.1371/journal.pone.0106238 · 3.23 Impact Factor
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    • "The partial or complete recovery of function underlies the plasticity of the brain and functional imaging studies have confirmed the ability of neural circuits to reorganize post-injury to recapitulate function [3]. Although it remains debatable whether functional recovery involves the production of new neurons in the adult brain [4], it is established that many forms of experimental brain trauma activate quiescent neural stem cells (NSCs) to increase neuronal progenitor cell proliferation in the adult rodent brain [5-8]. "
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    ABSTRACT: Experimental brain trauma activates quiescent neural stem cells (NSCs) to increase neuronal progenitor cell proliferation in the adult rodent brain. Previous studies have shown focal brain contusion in the form of a unilateral controlled cortical impact (CCI) stimulates NSCs to bilaterally increase neurogenesis in the adult hippocampus. In this study we clarified the bi-lateral effects of a unilateral CCI on proliferation in the subventricular zone (SVZ) NSC niche and on neurogenesis in the olfactory bulb of adult mice. By varying the depth of impact from 1 mm to 2 mm depth, we show CCI to the left somatosensory cortex resulted in graded changes in mouse behavior and cellular pathology in the forebrain. As expected, contusion to the sensorimotor cortex resulted in motor coordination deficits in adult mice. During the first 3 days after injury, CCI increased proliferation in the impacted cortex, deeper striatum and SVZ of the forebrain ipsilateral to the CCI. In each of these regions proliferation was increased with increasing injury severity. At 30 days post-procedure, CCI resulted in a significant reduction in neurogenesis in the olfactory bulb ipsilateral to the CCI. Olfactory avoidance testing indicated disruptions in olfactory bulb neurogenesis were associated with impaired olfactory discrimination in mice post-injury. The data demonstrate a focal cortical contusion injury to the left somatosensory cortex disrupts SVZ-olfactory bulb neurogenesis and impairs olfactory discrimination and motor coordination in adult mice.
    BMC Neuroscience 11/2013; 14(1):142. DOI:10.1186/1471-2202-14-142 · 2.67 Impact Factor
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    ABSTRACT: Our previous study demonstrates that delayed (initiated 24h post injury) erythropoietin (EPO) therapy for traumatic brain injury (TBI) significantly improves spatial learning. In this study, we investigated the impact of inhibition of EPO treatment-mediated neurogenesis on spatial learning after experimental TBI. Young male Wistar rats (318+/-7 g) were subjected to unilateral controlled cortical impact injury. TBI rats received delayed EPO treatment (5000 U/kg in saline) administered intraperitoneally once daily at 1, 2, and 3 days post injury and intracerebroventricular (icv) infusion of either a mitotic inhibitor cytosine-b-D-arabinofuranoside or vehicle (saline) for 14 days. Another 2 groups of TBI rats were treated intraperitoneally with saline and infused icv with either a mitotic inhibitor Ara-C or saline for 14 days. Animals receiving sham operation were infused icv with either Ara-C infusion or saline. Bromodeoxyuridine (BrdU) was administered to label dividing cells. Spatial learning was assessed using a modified Morris water maze test. Animals were sacrificed at 35 days after injury and brain sections stained for immunohistochemical analyses. As compared to the saline treatment, immunohistochemical analysis revealed that delayed EPO treatment significantly increased the number of BrdU-positive cells and new neurons co-stained with BrdU and NeuN (mature neuron marker) in the dentate gyrus in TBI rats. EPO treatment improved spatial learning after TBI. Ara-C infusion significantly abolished neurogenesis and spatial learning recovery after TBI and EPO treatment. Both EPO and Ara-C reduced the number of astrocytes and microglia/macrophages in the dentate gyrus after TBI. Our findings are highly suggestive for an important role of EPO-amplified dentate gyrus neurogenesis as one of the mechanisms underlying EPO therapeutic treatments after TBI, strongly indicating that strategies promoting endogenous neurogenesis may hold an important therapeutic potential for treatment of TBI.
    Experimental Neurology 03/2012; 235(1):336-44. DOI:10.1016/j.expneurol.2012.02.015 · 4.70 Impact Factor
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