Journal of neurotrauma
-
Journal of neurotrauma · May 2009
Intrathecal morphine attenuates recovery of function after a spinal cord injury.
Prior work has shown that a high dose (20 mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24 h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. ⋯ Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord.
-
Journal of neurotrauma · May 2009
Cytoskeletal and activity-related changes in spinal motoneurons after root avulsion.
Compelling evidence shows that after root avulsion motoneurons attempt to survive and regenerate before dying. In order to study these mechanisms, unilateral avulsion of L4-L5 spinal roots was performed in adult rats, and the ventral spinal cords were studied from 3 to 28 days post-operation (dpo). Electrophysiological results indicated complete denervation of L4-L5 muscles in the injured limb without functional effects on the contralateral hindlimb. ⋯ Intense SMI32 immunostaining was observed during the first week after avulsion, appearing in 37% (+/-0.9) of surviving motoneurons, but it was not associated with GAP43 expression. Calcitonin gene-related peptide (CGRP) expression in motoneurons was markedly reduced from the second week after avulsion. This study presents a detailed description of motoneuron reaction after root avulsion, which suggests an early time-window during the first 2 weeks for attempts to repair the injury and promote motoneuron survival and regeneration.
-
Journal of neurotrauma · May 2009
A novel protein complex in membrane rafts linking the NR2B glutamate receptor and autophagy is disrupted following traumatic brain injury.
Hyperactivation of N-methyl-D-aspartate receptors (NRs) is associated with neuronal cell death induced by traumatic brain injury (TBI) and many neurodegenerative conditions. NR signaling efficiency is dependent on receptor localization in membrane raft microdomains. Recently, excitotoxicity has been linked to autophagy, but mechanisms governing signal transduction remain unclear. ⋯ Moderate TBI induced rapid recruitment and association of NR2B and pCaMKII to membrane rafts, and translocation of Beclin-1 out of membrane microdomains. Furthermore, TBI caused significant increases in expression of key autophagic proteins and morphological hallmarks of autophagy that were significantly attenuated by treatment with the NR2B antagonist Ro 25-6981. Thus, stimulation of autophagy by NR2B signaling may be regulated by redistribution of Beclin-1 in membrane rafts after TBI.