Journal of neurotrauma
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Spinal cord injury (SCI) researchers have predominately utilized rodents and mice for in vivo SCI modeling and experimentation. From these small animal models have come many insights into the biology of SCI, and a growing number of novel treatments that promote behavioral recovery. It has, however, been difficult to demonstrate the efficacy of such treatments in human clinical trials. ⋯ Histological analysis of the spinal cords 12 weeks post-injury revealed that animals with the more biomechanically severe injuries had less spared white matter and gray matter and less neurofilament immunoreactivity. Additionally, the PTIBS scores correlated strongly with the extent of tissue sparing through the epicenter of injury. This large animal model of SCI may represent a useful intermediary in the testing of novel pharmacological treatments and cell transplantation strategies.
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Journal of neurotrauma · Feb 2013
The dual cyclooxygenase/5-lipoxygenase inhibitor licofelone attenuates p-glycoprotein-mediated drug resistance in the injured spinal cord.
There are currently no proven effective treatments that can improve recovery of function in spinal cord injury (SCI) patients. Many therapeutic compounds have shown promise in pre-clinical studies, but clinical trials have been largely unsuccessful. P-glycoprotein (Pgp, Abcb1b) is a drug efflux transporter of the blood-spinal cord barrier that limits spinal cord penetration of blood-borne xenobiotics. ⋯ Because inflammation can drive Pgp upregulation, we evaluated the ability of the new generation dual anti-inflammatory drug licofelone to promote spinal cord delivery of riluzole following SCI. We found that licofelone both reduced Pgp expression and enhanced riluzole bioavailability within the lesion site at 72 h post-SCI. This work highlights Pgp-mediated drug resistance as an important obstacle to therapeutic drug delivery for SCI, and suggests licofelone as a novel combinatorial treatment strategy to enhance therapeutic drug delivery to the injured spinal cord.
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Journal of neurotrauma · Feb 2013
Dynamic motor compensations with permanent, focal loss of forelimb force after cervical spinal cord injury.
Incomplete cervical lesion is the most common type of human spinal cord injury (SCI) and causes permanent paresis of arm muscles, a phenomenon still incompletely understood in physiopathological and neuroanatomical terms. We performed spinal cord hemisection in adult rats at the caudal part of the segment C6, just rostral to the bulk of triceps brachii motoneurons, and analyzed the forces and kinematics of locomotion up to 4 months postlesion to determine the nature of motor function loss and recovery. A dramatic (50%), immediate and permanent loss of extensor force occurred in the forelimb but not in the hind limb of the injured side, accompanied by elbow and wrist kinematic impairments and early adaptations of whole-body movements that initially compensated the balance but changed continuously over the follow-up period to allow effective locomotion. ⋯ Ipsilateral foreleg deficits resulted mainly from interruption of axons that innervate the spinal cord segments caudal to the lesion, because chronic loss (about 35%) of synapses was detected at C7 while only 14% of triceps braquii motoneurons died, as assessed by synaptophysin immunohistochemistry and retrograde neural tracing, respectively. We also found a large pool of propriospinal neurons projecting from C2-C5 to C7 in normal rats, with topographical features similar to the propriospinal premotoneuronal system of cats and primates. Thus, concurrent axotomy at C6 of brain descending axons and cervical propriospinal axons likely hampered spontaneous recovery of the focal neurological impairments.
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Journal of neurotrauma · Feb 2013
Sialidase, chondroitinase ABC, and combination therapy after spinal cord contusion injury.
Axon regeneration in the central nervous system is severely hampered, limiting functional recovery. This is in part because of endogenous axon regeneration inhibitors that accumulate at the injury site. Therapeutic targeting of these inhibitors and their receptors may facilitate axon outgrowth and enhance recovery. ⋯ Sialidase-treated rats also had increased serotonergic axons caudal to the injury. ChABC treatment, in contrast, did not enhance functional recovery or alter axon numbers after moderate spinal cord contusion injury, and dampened the response of sialidase in the dual enzyme treatment group. We conclude that sialidase infusion enhanced recovery from spinal cord contusion injury, and that combining sialidase with ChABC failed to improve outcomes.
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Journal of neurotrauma · Jan 2013
Bone flap resorption: risk factors for the development of a long-term complication following cranioplasty after decompressive craniectomy.
Aseptic bone flap resorption (BFR) is a known long-term complication after cranioplasty (CP). We analyzed our institutional data in order to identify risk factors for BFR. From October 1999 to April 2012, 254 patients underwent CP after decompressive craniectomy (DC) at our institution, and had a long-term follow-up period of >1 year after CP (range 12-146 months). ⋯ Furthermore, BFR developed significantly more often in patients who underwent cranioplasty ≤2 months after DC (p=0.008), as well as in patients with wound healing disturbance or abscess as an early complication after the CP procedure (p=0.01). The multivariate analysis of the present data identified the presence of multiple fractures within the bone flap (p=0.002, OR 10.3, 95% CI 2.4-43.8), wound infection after CP (p=0.003, OR 12.3, 95% CI 2.3-65.3), and cranioplasty performed ≤2 months after DC (p=0.01, OR 6.3, 95% CI 1.5-26.3) as independent risk factors for the development of BFR after CP in a large series with long-term follow-up. This might influence future surgical decision making, especially in patients fulfilling high risk criteria for developing BFR.