Journal of neurotrauma
-
Journal of neurotrauma · Apr 2011
Spinal cord injuries induce changes in CB1 cannabinoid receptor and C-C chemokine expression in brain areas underlying circuitry of chronic pain conditions.
Due to their involvement in neuro-modulatory processes, the endogenous cannabinoid system and chemokine network, which were shown to interact which each other, are potential key elements in the cascades underlying central neuropathic pain development after spinal cord injury (SCI). Expression profiles of cannabinoid receptor type-1 (CB(1)), and of the chemokines chemokine ligand 2 (C-C motif ) (CCL2), chemokine ligand 3 (C-C motif ) (CCL3), plus their main receptors CCR2 and CCR1, were investigated in brain regions related to pain, emotion, learning, and memory in a rat SCI paradigm of post-traumatic neuropathic pain. Immunoreactivity (IR) was investigated 7 days and 42 days after sham operation, and moderate (100-kdyn), and severe (200-kdyn) thoracic spinal cord contusion lesions. ⋯ Double-labeling revealed partial co-expression of CB(1) with the pain-related vanilloid receptor transient receptor potential vanilloid receptor 1 (TRPV1), and chemokines (CCL2 and CCL3). These chemokines were induced in the PAG, thalamus, and HC, especially in the chronic time course after severe SCI. Thus interactions of CB(1), C-C chemokines, and TRPV1 likely play a role in SCI-induced plastic changes in the brain, underlying emotional-affective pain responses and central pain development after spinal cord lesions.
-
Journal of neurotrauma · Mar 2011
Stereology and ultrastructure of chronic phase axonal and cell soma pathology in stretch-injured central nerve fibers.
Magnetic resonance imaging (MRI) suggests that with survival after human traumatic brain injury (TBI), there is ongoing loss of white and grey matter from the injured brain during the chronic phase. However; direct quantitative experimental evidence in support of this observation is lacking. Using the guinea pig stretch-injury optic nerve model, quantitative evidence by stereology of damage to the optic nerve and retina was sought. ⋯ There was hypertrophy and proliferation of glial cells within the surrounding neuropil. A relatively low-grade loss of retinal ganglion cells occurred throughout the experiment, with about 60% remaining at 12 weeks' survival. We provide quantitative evidence that after traumatic axonal injury (TAI) there is a continuing loss of nerve fibers and their cell bodies from a CNS tract over a 3-month post-traumatic interval.
-
Journal of neurotrauma · Mar 2011
Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury.
Spinal cord injury (SCI) often results in a loss of motor and sensory function. Currently there are no validated effective clinical treatments. Previously we found in rats that dietary restriction, in the form of every-other-day fasting (EODF), started prior to (pre-EODF), or after (post-EODF) an incomplete cervical SCI was neuroprotective, increased plasticity, and promoted motor recovery. ⋯ Behaviorally, both pre- and post-EODF groups exhibited better functional recovery in the regularity indexed BBB ambulatory assessment, along with several parameters of their walking pattern measured with the CatWalk device, compared to both the ad-libitium-fed group as well as the pair-fed group. Several histological parameters (intensity and symmetry of serotonin immunostaining caudal to the injury and gray matter sparing) correlated with functional outcome; however, no group differences were observed. Thus besides the beneficial effects of EODF after a partial cervical SCI, we now report that alternating periods of fasting (but not pair-fed) also promotes improved hindlimb locomotion after thoracic spinal cord contusion, demonstrating its robust effect in two different injury models.
-
Journal of neurotrauma · Mar 2011
Development of a chronic cervical cord compression model in rat: changes in the neurological behaviors and radiological and pathological findings.
Cervical myelopathy is caused by chronic segmental compression of the spinal cord because of degenerative changes of the spine. However, the exact mechanisms of chronic cervical cord compression are not fully understood. The purpose of this study was to validate a new animal model of chronic cervical cord compression capable of reproducing the clinical course without laminectomy in rats. ⋯ In histological sections, the spinal cord was compressed along the entire circumference at 12 months after initiating CCS. The number of ventral neurons was decreased, and the white matter showed wallerian degeneration. This model might reproduce characteristic features of clinical chronic cervical cord compression, including progressive motor and sensory disturbances after a latency period and insidious neuronal loss, and represents chronic compression of the cervical spinal cord in humans.
-
Journal of neurotrauma · Mar 2011
Glucagon protects against impaired NMDA-mediated cerebrovasodilation and cerebral autoregulation during hypotension after brain injury by activating cAMP protein kinase A and inhibiting upregulation of tPA.
Outcome of traumatic brain injury (TBI) is impaired by hyperglycemia, hypotension, and glutamate, and improved by insulin. Insulin reduces glutamate concentration, making it uncertain whether its beneficial effect accrues from euglycemia. Glucagon decreases CNS glutamate, lessens neuronal cell injury, and improves neurological scores in mice after TBI. ⋯ Co-administration of the PKA antagonist Rp 8Br cAMPs prevented glucagon-mediated preservation of NMDA-mediated dilation after FPI. The pKA agonist Sp 8Br cAMPs prevented impairment of NMDA-induced dilation. These data indicate that glucagon protects against impaired cerebrovasodilation by upregulating cAMP, which decreases release of tPA, suggesting that it may provide neuroprotection when given after TBI, or prior to certain neurosurgical or cardiac interventions in which the incidence of perioperative ischemia is high.