Journal of neurotrauma
-
Journal of neurotrauma · Sep 2011
Transplanted L1 expressing radial glia and astrocytes enhance recovery after spinal cord injury.
A major obstacle for the transplantation of neural stem cells (NSCs) into the lesioned spinal cord is their predominant astrocytic differentiation after transplantation. We took advantage of this predominant astrocytic differentiation of NSCs and expressed the paradigmatic beneficial neural cell adhesion molecule L1 in radial glial cells and reactive and nonreactive astrocytes as novel cellular vehicles to express L1 under the control of the promoter for the human glial fibrillary acidic protein (GFAP-L1 NSCs). ⋯ Morphological analysis revealed that mice grafted with GFAP-L1 NSCs exhibited increased neuronal differentiation and migration of transplanted cells, as well as increased soma size and cholinergic synaptic coverage of host motoneurons and increased numbers of endogenous catecholaminergic nerve fibers caudal to the lesion site. These findings show that L1-expressing astrocytes and radial glial cells isolated from GFAP-L1 NSC cultures represent a novel strategy for improving functional recovery after spinal cord injury, encouraging the use of the human GFAP promoter to target beneficial transgene expression in transplanted stem cells.
-
Journal of neurotrauma · Sep 2011
The association between apolipoprotein E and traumatic brain injury severity and functional outcome in a rehabilitation sample.
Traumatic brain injury (TBI) can result in significant disability, but outcome is variable. The impact of known predictors accounts for a limited proportion of the variance in outcomes. Apolipoprotein E (ApoE) genotype has been investigated as an additional source of variability in injury severity and outcome, with mixed findings reflecting variable methodology and generally limited sample sizes. ⋯ Prediction of worse Glasgow Outcome Scale-Extended (GOSE) scores for ɛ4 carriers was supported with greater susceptibility seen in females. These results indicate the ApoE ɛ4 allele may be associated with poorer long-term outcome, but not acute injury severity. Possible mechanisms include differential effects of the ɛ4 allele on inflammatory and cellular repair processes, and/or amyloid deposition.
-
Journal of neurotrauma · Sep 2011
Anti-inflammatory treatments during the chronic phase of spinal cord injury improve locomotor function in adult mice.
Our previous data suggested that ongoing inflammation in the spinal cord 6 weeks following spinal cord injury was detrimental to locomotor function. Others have shown in the acute and sub-acute post-injury phase that microglial/macrophage activation and T regulatory cells are detrimental to recovery. Here, C57BL/6 mice with a moderately severe T9 contusion were injected intravenously daily with minocycline, which reduces microglial/macrophage activation, or with CD25 antibodies, which reduce T regulatory cell function, starting at 6 weeks after injury. ⋯ The effects diminished within 1 week after termination of the treatments, suggesting an ongoing and dynamic inflammatory process. The area of white matter or the inflammatory markers CD68 for activated microglia/macrophages and CD45 for leukocytes were not different between the groups. These data suggest that inflammation during the chronic phase following spinal cord injury reduces conduction through the epicenter, possibly by release of cytokines, and is amenable to treatment for improved neurological function.
-
Journal of neurotrauma · Sep 2011
Ethanol intoxication is associated with a lower incidence of admission coagulopathy in severe traumatic brain injury patients.
The aim of this study was to determine the impact of ethanol (ETOH) on the incidence of severe traumatic brain injury (sTBI)-associated coagulopathy and to examine the effect of ETOH on in-hospital outcomes in patients sustaining sTBI. Patients admitted to the surgical intensive care unit from June 2005 through December 2008 following sTBI, defined as a head Abbreviated Injury Scale (AIS) score ≥3, were retrospectively identified. Patients with a chest, abdomen, or extremity AIS score >3 were excluded to minimize the impact of extracranial injuries. ⋯ ETOH (+) patients had a significantly lower in-hospital mortality rate than ETOH (-) patients [9.8% versus 16.6%; adjusted p=0.011; adjusted OR (95% CI)=0.39 (0.19,0.81)]. For brain-injured patients arriving alive to the hospital, ETOH intoxication is associated with a significantly lower incidence of early coagulopathy and in-hospital mortality. Further research to establish the pathophysiologic mechanisms underlying any potential beneficial effect of ETOH on the coagulation system following sTBI is warranted.
-
Journal of neurotrauma · Sep 2011
Post-injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats.
Mitochondrial dysfunction is known to play a pivotal role in cell death mechanisms following traumatic brain injury (TBI). N-methyl-4-isoleucine-cyclosporin (NIM811), a non-immunosuppressive cyclosporin A (CsA) analog, inhibits the mitochondrial permeability transition pore (mPTP) and has been shown to be neuroprotective following TBI in mice. However, the translation of the neuroprotective effects of mPTP inhibitors, including CsA and NIM811, into improved cognitive end points has yet to be fully investigated. ⋯ For behavioral studies, rats were administered NIM811 at 15 min and 24 h post-injury, with cognitive testing beginning 10 days post-injury. Mitochondrial studies involved a single injection of NIM811 at 15 min post-injury followed by mitochondrial isolation at 6 h post-injury. The results revealed that the optimal dose of NIM811 improves cognition, improves mitochondrial functioning, and reduces oxidative damage following TBI.