Articles: traumatic-brain-injuries.
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Traumatic brain injury (TBI) is characterized by neuronal damage and commonly, secondary cell death, leading to functional and neurological dysfunction. Despite the recent focus of TBI research on developing therapies, affective therapeutic strategies targeting neuronal death associated with TBI remain underexplored. This study explored the efficacy of granulocyte-colony stimulating factor (G-CSF) as an intervention for improving cognitive deficits commonly associated with TBI. ⋯ The Morris Water Maze test was used to measure any treatment-associated changes in cognitive deficits observed in TBI animals at days 2-6 post-injury. Our findings demonstrate a significant improvement in cognitive performance in the G-CSF treated TBI animals within a week of injury, compared to untreated TBI, indicative of immediate and beneficial effect of G-CSF on cognitive performance post CHI. Our model suggests that early G-CSF exposure may be a promising therapeutic approach in recovery of cognitive deficits due to TBI.
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Clin. Exp. Pharmacol. Physiol. · Feb 2014
Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.
Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. ⋯ Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI.
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Early recovery from incomplete spinal cord contusion is improved by prolonged stimulation of the hindbrain's serotonergic nucleus raphe magnus (NRM). Here we examine whether increases in cyclic adenosine monophosphate (cAMP), an intracellular signaling molecule with several known restorative actions on damaged neural tissue, could play a role. Subsequent changes in cAMP-dependent phosphorylation of protein kinase A (PKA) and PKA-dependent phosphorylation of the transcription factor "cAMP response element-binding protein" (CREB) are also analyzed. ⋯ The phosphorylated fraction of PKA (pPKA) and CREB (pCREB) was reduced significantly in all three regions after SCI and restored by NRM stimulation, except for pCREB in lumbar segments. In conclusion, SCI produces spreading deficits in cAMP, pPKA and pCREB that are reversible by Gs protein-coupled 5-HT receptors responding to raphe-spinal activity, although these signaling molecules are not reactive to NRM stimulation in normal tissue. These findings can partly explain the benefits of NRM stimulation after SCI.
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Nogo-A is a major form of growth inhibitory molecule (growth-IM) which inhibits axonal regeneration and neurite regrowth after neural injury. Bone marrow stromal cells (MSCs) have been shown to inhibit Nogo-A expression in vitro and in cerebral ischemic animal models. The present study was designed to investigate the effects of treatment with human MSCs (hMSCs) impregnated into collagen scaffolds on the expression of Nogo-A and axonal plasticity after traumatic brain injury (TBI). ⋯ In addition, scaffold+hMSC transplantation decreased Nogo-A transcription in oligodendrocytes after TBI. Scaffold+hMSC treatment was superior to hMSC-alone treatment in suppressing Nogo-A expression and enhancing axonal regeneration after TBI. Our data suggest that transplanting hMSCs with scaffolds down-regulates Nogo-A transcription and protein expression which may partially contribute to the enhanced axonal regeneration after TBI.
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The evidence that BDNF is involved in neuroprotection, neuronal repair and recovery after traumatic brain injury (TBI) is substantial. We have previously shown that the polymorphism of the human BDNF gene predicts cognitive recovery and outcome following penetrating TBI. The distribution of expression of BDNF and its receptors after penetrating TBI has not been investigated. ⋯ Our study is the first report on the expression of BDNF and its receptors following penetrating TBI and suggests that their expression is altered long after the acute phase of injury. Further studies are needed to investigate if the late expressions of these receptors are beneficial or deleterious. In either case it indicates the possibility to influence the recovery after brain injury during the chronic phase and the development of treatments that may improve the outcome of TBI patients.