Journal of neurotrauma
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Journal of neurotrauma · Feb 2018
Rolipram-loaded polymeric micelle nanoparticle reduces secondary injury after rat compression spinal cord injury.
Among the complex pathophysiological events following spinal cord injury (SCI), one of the most important molecular level consequences is a dramatic reduction in neuronal cyclic adenosine monophosphate (cAMP) levels. Many studies shown that rolipram (Rm), a phosphodiesterase IV inhibitor, can protect against secondary cell death, reduce inflammatory cytokine levels and immune cell infiltration, and increase white matter sparing and functional improvement. Previously, we developed a polymeric micelle nanoparticle, poly(lactide-co-glycolide)-graft-polyethylenimine (PgP), for combinatorial delivery of therapeutic nucleic acids and drugs for SCI repair. ⋯ After intraspinal injection, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine Iodide-loaded PgP micelles were retained at the injection site for up to 5 days. Finally, we show that a single injection of Rm-PgP nanoparticles restored cAMP in the SCI lesion site and reduced apoptosis and the inflammatory response. These results suggest that PgP may offer an efficient and translational approach to delivering Rm as a neuroprotectant following SCI.
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Journal of neurotrauma · Feb 2018
Lentivirus mediating FGF13 enhances axon regeneration after spinal cord injury by stablilizing microtubule and improving mitochondrial function.
Fibroblast growth factor 13 (FGF13), a nonsecretory protein of the FGF family, plays a crucial role in developing cortical neurons by stabilizing the microtubule. In previous studies, we showed that regulation of microtubule dynamics was instrumental for both growth cone initiation and for promoting regrowth of injured axon. However, the expression and effect of FGF13 in spinal cord or after spinal cord injury (SCI) remains undefined. ⋯ Administration of FGF13 not only promoted neuronal polarization, axon formation, and growth cone initiation in vitro, but it also facilitated functional recovery following SCI. In addition, we found that upregulation of FGF13 in primary cortical neurons was accompanied by enhanced mitochondrial function, which is essential for axon regeneration. Our study has defined a novel mechanism underlying the beneficial effect of FGF13 on axon regeneration, pointing out that FGF13 may serve as a potential candidate for treating SCI or other central nervous system (CNS) injury.
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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
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.