Journal of neurotrauma
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Journal of neurotrauma · Feb 2018
Spinal cord injury causes systolic dysfunction and cardiomyocyte atrophy.
Individuals with spinal cord injury (SCI) have been shown to exhibit systolic, and to a lesser extent, diastolic cardiac dysfunction. However, previous reports of cardiac dysfunction in this population are confounded by the changing loading conditions after SCI and as such, whether cardiac dysfunction per se is present is still unknown. Therefore, our aim was to establish if load-independent cardiac dysfunction is present after SCI, to understand the functional cardiac response to SCI, and to explore the changes within the cellular milieu of the myocardium. ⋯ The reduction in contractile indices is accompanied by a reduction in width and length of cardiomyocytes as well as alterations in the LV extracellular matrix. Importantly, we demonstrate that the reduction in the rate (dP/dtmax) of LV pressure rise can be offset with beta-adrenergic stimulation, thereby experimentally implicating the loss of descending sympatho-excitatory control of the heart as a principle cause of LV dysfunction in SCI. Our data provide evidence that SCI induces systolic cardiac dysfunction independent of loading conditions and concomitant cardiomyocyte atrophy that may be underpinned by changes in the genes regulating the cardiac extracellular matrix.
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Journal of neurotrauma · Feb 2018
Spatial and cellular expression patterns of Erythropoietin-Receptor and Erythropoietin during a 42 day post-lesional time-course after graded thoracic spinal cord impact lesions in the rat.
Erythropoietin (Epo) exhibits promising neuroregenerative potential for spinal cord injury (SCI), and might be involved in other long-term sequelae, such as neuropathic pain development. The current studies investigated the time courses and spatial and cellular patterns of Epo and erythropoietin receptor (EpoR) expression along the spinal axis after graded SCI. Male Long Evans rats received 100 kdyn, 150 kdyn, and 200 kdyn thoracic (T9) contusions from an Infinite Horizon impactor. ⋯ The DC EpoR/Epo immunoreactivities exhibited linear relationships with the behavioral correlates of post-lesional chronic pain development at DPO 42. SCI leads to long-lasting multicellular EpoR/Epo induction beyond the lesion core in the spinal cord regions that are involved in central pain development and regenerative processes. Our studies provide a time frame to investigate the effects of Epo application on motor function or pain development, especially in the later time course after lesioning.
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Journal of neurotrauma · Feb 2018
Mithramycin A improves functional recovery by inhibiting BSCB disruption and hemorrhage after spinal cord injury.
After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption and progressive hemorrhage lead to secondary injury, subsequent apoptosis and/or necrosis of neurons and glia, causing permanent neurological deficits. Growing evidence indicates that mithramycin A (MA), an anti-cancer drug, has neuroprotective effects in ischemic brain injury and Huntington's disease (HD). However, the precise mechanism underlying its protective effects is largely unknown. ⋯ In addition, the expression of sulfonylurea receptor 1 (SUR1) and transient receptor potential melastatin 4 (TRPM4), which are known to mediate hemorrhage at an early stage after SCI, was significantly blocked by MA treatment. Finally, MA inhibited apoptotic cell death and improved functional recovery after injury. Thus, our results demonstrated that MA improves functional recovery by attenuating BSCB disruption and hemorrhage through the downregulation of SUR1/TRPM4 and MMP-9 after SCI.
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Journal of neurotrauma · Feb 2018
ReviewSpinal meninges and their role in spinal cord injury: A neuroanatomical review.
Current recommendations support early surgical decompression and blood pressure augmentation after traumatic spinal cord injury (SCI). Elevated intraspinal pressure (ISP), however, has probably been underestimated in the pathophysiology of SCI. Recent studies provide some evidence that ISP measurements and durotomy may be beneficial for individuals suffering from SCI. ⋯ In such cases, intentional durotomy with augmentative duroplasty to reduce ISP and improve spinal cord perfusion pressure (SCPP) may be indicated. Prior to performing these procedures routinely, profound knowledge of the spinal meninges is essential. Here, we provide an in-depth review of relevant literature along with neuroanatomical illustrations and imaging correlates.
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Journal of neurotrauma · Feb 2018
Clinical TrialBody System Effects of a Multi-Modal Training Program Targeting Chronic, Motor Complete Thoracic Spinal Cord Injury.
The safety and efficacy of pharmacological and cellular transplantation strategies are currently being evaluated in people with spinal cord injury (SCI). In studies of people with chronic SCIs, it is thought that functional recovery will be best achieved when drug or cell therapies are combined with rehabilitation protocols. However, any functional recovery attributed to the therapy may be confounded by the conditioned state of the body and by training-induced effects on neuroplasticity. ⋯ Changes in pain and spasticity were highly variable between participants. This is the first demonstration of the effect of this combination of four training modalities. However, balancing participant and study-site burden with capturing meaningful outcome measures is also an important consideration.