Experimental neurology
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Experimental neurology · Oct 2013
Genetically modified mesenchymal stem cells (MSCs) promote axonal regeneration and prevent hypersensitivity after spinal cord injury.
Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs) are both candidate therapies targeting spinal cord injury (SCI). While some studies have suggested the ability of MSCs to transdifferentiate into neural cells, other SCI studies have proposed anti-inflammatory and other mechanisms underlying established beneficial effects. We grafted rat MSCs genetically modified to express MNTS1, a multineurotrophin that binds TrkA, TrkB and TrkC, and p75(NTR) receptors or MSC-MNTS1/p75(-) that binds mainly to the Trk receptors. ⋯ Moreover, transplantation of MSC-MNTS1/p75(-) promoted angiogenesis and modified glial scar formation. These findings suggest that MSCs transduced with a multineurotrophin are effective in promoting cell growth and improving sensory function after SCI. These novel data also provide insight into the neurotrophin-receptor dependent mechanisms through which cellular transplantation leads to functional improvement after experimental SCI.
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Experimental neurology · Oct 2013
The role of the crossed phrenic pathway after cervical contusion injury and a new model to evaluate therapeutic interventions.
More than 50% of all spinal cord injury (SCI) cases are at the cervical level and usually result in the impaired ability to breathe. This is caused by damage to descending bulbospinal inspiratory tracts and the phrenic motor neurons which innervate the diaphragm. Most investigations have utilized a lateral C2 hemisection model of cervical SCI to study the resulting respiratory motor deficits and potential therapies. ⋯ This suggests an important modulatory role for these pathways. Additionally, we conclude that this dual injury, hemi-contusion and post contra-hemisection, is a more effective and relevant model of cervical SCI as it results in a more direct compromise of diaphragmatic motor activity. This model can thus be used to test potential therapies with greater accuracy and clinical relevance than cervical contusion models currently allow.
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Experimental neurology · Oct 2013
Early cognitive changes due to whole body γ-irradiation: a behavioral and diffusion tensor imaging study in mice.
Radiation-induced aberration in the neuronal integrity and cognitive functions are well known. However, there is a lacuna between sparsely reported immediate effects and the well documented delayed effects of radiation on cognitive functions. The present study was aimed at investigating the radiation-dose dependent incongruities in the early cognitive changes, employing two approaches, behavioral functions and diffusion tensor imaging (DTI). ⋯ The hippocampus emerged as one of the sensitive regions to be affected by whole-body exposure to gamma rays, which led to profound immediate alterations in cognitive functions. Furthermore, the results indicate a cognitive recovery process, which might be dependent on the extent of damage to the hippocampal region. The present study also emphasizes the importance of further research to unravel the complex pattern of neurobehavioral responses immediately following ionizing radiation exposure.
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Experimental neurology · Oct 2013
Prevention of rt-PA induced blood-brain barrier component degradation by the poly(ADP-ribose)polymerase inhibitor PJ34 after ischemic stroke in mice.
Recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment approved for thrombolysis in patients suffering from ischemic stroke, but its administration aggravates the risk of hemorrhagic transformations. Experimental data demonstrated that rt-PA increases the activity of poly(ADP-ribose)polymerase (PARP). The aim of the present study was to investigate whether PJ34, a potent (PARP) inhibitor, protects the blood-brain barrier components from rt-PA toxicity. ⋯ Combining PJ34 with rt-PA preserved the expression of ZO-1, claudin-5 and VE-cadherin, reduced the hemorrhagic transformations and improved the sensorimotor performances. In vitro studies also demonstrated that PJ34 crosses the blood-brain barrier and may thus exert its protective effect by acting on endothelial and/or parenchymal cells. Thus, co-treatment with a PARP inhibitor seems to be a promising strategy to reduce rt-PA-induced vascular toxicity after stroke.
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Experimental neurology · Oct 2013
Complementary roles of different oscillatory activities in the subthalamic nucleus in coding motor effort in Parkinsonism.
The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear. ⋯ Accordingly, the difference between power changes in the gamma and beta bands correlated with effort across all effort levels. These findings suggest complementary roles for changes in beta and gamma band activities in the STN in motor effort coding. The latter function is thought to be impaired in untreated PD where task-related reactivity in these two bands is deficient.