Experimental neurology
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Experimental neurology · Mar 2016
Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.
An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. ⋯ Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 min of daily stimulation compared with 6h, as in our prior study, making it a potential therapy for humans with spinal cord injury.
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Experimental neurology · Mar 2016
Neuroinflammation in primary blast neurotrauma: Time course and prevention by torso shielding.
Mechanisms of primary blast injury caused by overpressure are not fully understood. In particular, the presence and time course of neuroinflammation are unknown and so are the signatures of reactive inflammatory cells, especially the neuroprotective versus injurious roles of microglia. In general, chronic microglial activation in the injured brain suggests a pro-degenerative role for these reactive cells. ⋯ These findings shed light into mechanisms of primary blast neurotrauma and may suggest novel diagnostic and monitoring methods for patients. They leave open the question of whether microglial activation post blast is protective or detrimental, although response is time limited. Finally, our findings confirm the protective role of torso shielding and stress the importance of improved or optimized body gear for warfighters or other individuals at risk for blast exposure.
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Experimental neurology · Mar 2016
Diminished amygdala activation and behavioral threat response following traumatic brain injury.
Each year, approximately 3.8 million people suffer mild to moderate traumatic brain injuries (mTBI) that result in an array of neuropsychological symptoms and disorders. Despite these alarming statistics, the neurological bases of these persistent, debilitating neuropsychological symptoms are currently poorly understood. In this study we examined the effects of mTBI on the amygdala, a brain structure known to be critically involved in the processing of emotional stimuli. ⋯ Thus, not only does activation of the LA require increased stimulation, but the proportion of this activation that is propagated to the primary output of the amygdala, the central amygdala, is also diminished following LFPI. Intracellular recordings revealed no changes in the intrinsic properties of BLA pyramidal neurons after LFPI. This data suggests that mild to moderate TBI has prominent effects on amygdala function and provides a potential neurological substrate for many of the neuropsychological symptoms suffered by TBI patients.
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Experimental neurology · Mar 2016
Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis.
While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. ⋯ Exploratory global network analysis showed changes in network parameters indicative of possible acutely increased random connectivity and temporary reductions in modularity that were matched by local increases in connectedness and increased efficiency among more weakly connected regions. The global network parameters: shortest path-length, clustering coefficient and modularity that were most affected by trauma also scaled with the severity of injury, so that the corresponding regional measures were correlated to the injury severity most notably at 7 and 14 days and especially within, but not limited to, the contralateral cortex. These changes in functional network parameters are discussed in relation to the known time-course of physiologic and anatomic data that underlie structural and functional reorganization in this experiment model of TBI.
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Experimental neurology · Mar 2016
Effects of serum immunoglobulins from patients with complex regional pain syndrome (CRPS) on depolarisation-induced calcium transients in isolated dorsal root ganglion (DRG) neurons.
Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. ⋯ However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1 μM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested.