Journal of neurotrauma
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Journal of neurotrauma · Feb 2018
The relationship between lesion severity characterized by diffusion tensor imaging and motor function in chronic canine spinal cord injury.
Lesion heterogeneity among chronically paralyzed dogs after acute, complete thoracolumbar spinal cord injury (TLSCI) is poorly described. We hypothesized that lesion severity quantified by diffusion tensor imaging (DTI) is associated with hindlimb motor function. Our objectives were to quantify lesion severity with fractional anisotropy (FA), mean diffusivity (MD), and tractography and investigate associations with motor function. ⋯ The FA at the lesion epicenter and presence of translesional fibers were associated with OFS (p ≤ 0.0299). DTI can detect degeneration and physical transection after severe TLSCI. Findings suggest DTI quantifies injury severity and suggests motor recovery in apparently complete dogs is because of supraspinal input.
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Journal of neurotrauma · Feb 2018
Transient hypertension after spinal cord injury leads to cerebrovascular endothelial dysfunction and fibrosis.
We aimed to create a clinically relevant pre-clinical model of transient hypertension, and then evaluate the pathophysiological cerebrovascular processes resulting from this novel stimulus, which has recently been epidemiologically linked to cerebrovascular disease. We first developed a clinically relevant model of transient hypertension, secondary to induced autonomic dysreflexia after spinal cord injury and demonstrated that in both patients and rats, this stimulus leads to drastic acute cerebral hyperperfusion. For this, iatrogenic urodynamic filling/penile vibrostimulation was completed while measuring beat-by-beat blood pressure and cerebral blood flow (CBF) in patients. ⋯ Our model demonstrates that chronic repetitive cerebral hyperperfusion secondary to transient hypertension because of autonomic dysreflexia: (1) impairs cerebrovascular endothelial function; (2) leads to profibrotic cerebrovascular stiffening characterized by reduced distensibility and increased collagen deposition; and (3) reduces perivascular sympathetic cerebrovascular innervation. These changes did not occur concurrent to hallmark cerebrovascular changes from chronic steady-state hypertension, such as hypertrophic inward remodeling, or reduced CBF. Chronic exposure to repetitive transient hypertension after spinal cord injury leads to diverse cerebrovascular impairment that appears to be unique pathophysiology compared with steady-state hypertension in non-spinal cord injured models.
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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
Diaphragm and intercostal muscle activity following mid-cervical spinal cord contusion in the rat.
The present study was designed to investigate the diaphragm and intercostal muscle activity after unilateral mid-cervical spinal cord contusion in rats. Electromyogram (EMG) activity of the bilateral diaphragm and T2 intercostal muscle was measured in anesthetized and spontaneously breathing rats. Unilateral mid-cervical contusion caused an immediate reduction in inspiratory bursting in the bilateral diaphragm and intercostal muscles. ⋯ Notably, intercostal muscle activity was not substantially changed by mid-cervical spinal cord contusion from 3 days to 8 weeks post-contusion. These results suggest that mid-cervical spinal contusion induces a compensatory increase in contralateral diaphragmatic activity and greater utilization of a percentage of maximal inspiratory activity in the ipsilateral diaphragm. The maintenance of intercostal muscle activity may enable the animal to sustain essential breathing capacity after cervical spinal cord injury.