Journal of neurotrauma
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Journal of neurotrauma · Feb 2017
Systemic administration of Connexin43 mimetic peptide improves functional recovery following traumatic spinal cord injury in adult rats.
Blocking of Connexin43 hemichannels, the main gap junction protein located on astrocytes in the central nervous system, has been shown to reduce neural injury in a number of models. We demonstrated previously that local administration of a Connexin43 mimetic peptide, Peptide5, reduces secondary tissue damage after spinal cord injury (SCI). Here, we investigated whether acute systemic delivery of Peptide5 is also protective in a model of SCI. ⋯ At two and six weeks, lesion size, the astrocytic and the activated macrophage, and/or microglial response were all decreased in the Peptide5 animals. In addition, neuronal cell numbers were higher in the Peptide5 animals compared with the scrambled peptide treated rats at two and six weeks. These results show for the first time that systemic administration of Peptide5 to block the pathological opening of Connexin43 hemichannels is a feasible treatment strategy in this setting, ameliorating the secondary SCI.
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Journal of neurotrauma · Jan 2017
GFAP and UCH-L1 are not specific biomarkers for mild CT-negative traumatic brain injury.
Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) have been studied as potential biomarkers of mild traumatic brain injury (mTBI). We report the levels of GFAP and UCH-L1 in patients with acute orthopedic injuries without central nervous system involvement, and relate them to the type of extracranial injury, head magnetic resonance imaging (MRI) findings, and levels of GFAP and UCH-L1 in patients with CT-negative mTBI. Serum UCH-L1 and GFAP were longitudinally measured from 73 patients with acute orthopedic injury on arrival and on days 1, 2, 3, 7 after admission, and on the follow-up visit 3-10 months after the injury. ⋯ Levels of GFAP and UCH-L1 were not able to distinguish patients with CT-negative mTBI from patients with orthopedic trauma. Patients with orthopedic trauma and high levels of UCH-L1 or GFAP values may be falsely diagnosed as having a concomitant mTBI, predisposing them to unwarranted diagnostics and unnecessary brain imaging. This casts a significant doubt on the diagnostic value of GFAP and UCH-L1 in cases with mTBI.
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Journal of neurotrauma · Jan 2017
The therapeutic efficacy of environmental enrichment and methylphenidate alone and in combination after controlled cortical impact injury.
Environmental enrichment (EE) and methylphenidate (MPH) independently confer significant benefit to behavioral recovery after controlled cortical impact (CCI) injury. Given that combinational therapies may be more clinically translatable than monotherapies, the aim of the current study was to test the hypothesis that a combined treatment regimen of EE and MPH would provide greater therapeutic efficacy than either one alone. Anesthetized adult male rats received either a CCI of moderate severity or sham injury and were then randomly assigned to EE or standard (STD) housing where they received either intraperitoneal (ip) MPH (5 mg/kg) or vehicle (VEH; 1.0 mL/kg; ip) beginning 24 h after injury and once daily for 19 days. ⋯ In addition, both EE groups performed significantly better than the TBI+STD+MPH group (p < 0.05), but did not differ from one another (p > 0.05). These data replicate previous findings that both EE and MPH confer cognitive benefits after TBI and extend the findings by revealing that combining EE and MPH does not produce effects greater than either treatment alone, which does not support the hypothesis. The lack of an additive effect may be because of the robustness of the EE.
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Journal of neurotrauma · Jan 2017
Striatal Mitochondrial Disruption Following Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) results in oxidative stress and calcium dysregulation in mitochondria. However, little work has examined perturbations of mitochondrial homeostasis in peri-injury tissue. We examined mitochondrial homeostasis after a unilateral controlled cortical impact over the sensorimotor cortex in adult male rats. ⋯ We detected an acute increase in superoxide dismutase 2 mRNA expression, as well as an induction of microRNA (miR)-21 and miR-155, which have been previously demonstrated to disrupt mitochondrial homeostasis. Behaviorally, rats with TBI exhibited marked error rates in contrainjury forelimb performance on the ladder test. These findings reveal that there may be differential susceptibilities of various peri-injury brain structures to mitochondrial dysfunction and associated behavioral deficits, and that molecular pathways demonstrated to interfere with mitochondrial homeostasis and function are activated subacutely post-TBI.
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Journal of neurotrauma · Jan 2017
The Effect of Underwater Blast on Aggregating Brain Cell Cultures.
Although the deleterious effects of primary blast on gas-filled organs are well accepted, the effect of blast-induced shock waves on the brain is less clear because of factors that complicate the interpretation of clinical and experimental data. Brain cell aggregate cultures are comprised of multiple differentiated brain cell types and were used to examine the effects of underwater blast. Suspensions of these cultures encased in dialysis tubing were exposed to explosive-generated underwater blasts of low (∼300 kPa), medium (∼2,700 kPa), or high (∼14,000 kPa) intensities and harvested at 1-28 days post-exposure. ⋯ The free-floating nature of the aggregates during blast wave exposure, coupled with their highly hydrolyzed dialysis tubing containment, results in minimized boundary effects, thus enabling accurate assessment of brain cell response to a simplified shock-induced stress wave. This work shows that, at its simplest, blast-induced shock waves produce subtle changes in brain tissue. This study has mechanistic implications for the study of primary blast-induced traumatic brain injury and supports the thesis that underwater blast may cause subtle changes in the brains of submerged individuals.