Journal of neurotrauma
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Journal of neurotrauma · Apr 2014
Traumatic brain injury in vivo and in vitro contributes to cerebral vascular dysfunction through impaired gap junction communication between vascular smooth muscle cells.
Gap junctions (GJs) contribute to cerebral vasodilation, vasoconstriction, and, perhaps, to vascular compensatory mechanisms, such as autoregulation. To explore the effects of traumatic brain injury (TBI) on vascular GJ communication, we assessed GJ coupling in A7r5 vascular smooth muscle (VSM) cells subjected to rapid stretch injury (RSI) in vitro and VSM in middle cerebral arteries (MCAs) harvested from rats subjected to fluid percussion TBI in vivo. Intercellular communication was evaluated by measuring fluorescence recovery after photobleaching (FRAP). ⋯ In isolated MCAs from rats treated with the ONOO(-) scavenger, penicillamine, GJ coupling was not impaired by fluid percussion TBI. In addition, penicillamine treatment improved vasodilatory responses to reduced intravascular pressure in MCAs harvested from rats subjected to moderate fluid percussion TBI. These results indicate that TBI reduced GJ coupling in VSM cells in vitro and in vivo through mechanisms related to generation of the potent oxidant, ONOO(-).
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Journal of neurotrauma · Apr 2014
PARP-1 Inhibition Attenuates Neuronal Loss, Microglia Activation and Neurological Deficits after Traumatic Brain Injury.
Traumatic brain injury (TBI) causes neuronal cell death as well as microglial activation and related neurotoxicity that contribute to subsequent neurological dysfunction. Poly (ADP-ribose) polymerase (PARP-1) induces neuronal cell death through activation of caspase-independent mechanisms, including release of apoptosis inducing factor (AIF), and microglial activation. Administration of PJ34, a selective PARP-1 inhibitor, reduced cell death of primary cortical neurons exposed to N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG), a potent inducer of AIF-dependent cell death. ⋯ Stereological analysis demonstrated that PJ34 treatment reduced the lesion volume, attenuated neuronal cell loss in the cortex and thalamus, and reduced microglial activation in the TBI cortex. PJ34 treatment did not improve cognitive performance in a Morris water maze test or reduce neuronal cell loss in the hippocampus. Overall, our data indicate that PJ34 has a significant, albeit selective, neuroprotective effect after experimental TBI, and its therapeutic effect may be from multipotential actions on neuronal cell death and neuroinflammatory pathways.
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Journal of neurotrauma · Apr 2014
Assessment of an Experimental Rodent Model of Pediatric Mild Traumatic Brain Injury.
Childhood is one the highest risk periods for experiencing a mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls. In addition, many children experience lingering symptomology (post-concussion syndrome) from these closed head injuries. Although the negative sequel of mTBI has been described, a clinically reliable animal model of mild pediatric brain injury has not. ⋯ Juvenile rats who experienced a single mTBI displayed significant motor/balance impairments when tested on the beam walking task and in the open field, as well as deficits of executive functioning as measured with the novel context mismatch task and the probe trial of the Morris water task. In addition, both male and female rats showed depression-like behavior in the forced swim task, with male rats also exhibiting decreased anxiety-related behaviors in the elevated plus maze. The results from this study suggest that the modified weight-drop technique induces a clinically relevant behavioral phenotype in juvenile rats, and may provide researchers with a reliable animal model of mTBI/concussion from which clinical therapeutic strategies could be developed.
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Journal of neurotrauma · Apr 2014
Randomized Controlled Trial Multicenter StudyEarly Trajectory of Psychiatric Symptoms After Traumatic Brain Injury: Relationship to Patient and Injury Characteristics.
Psychiatric disturbance is common and disabling after traumatic brain injury (TBI). Few studies have investigated the trajectory of psychiatric symptoms in the first 6 months postinjury, when monitoring and early treatment might prevent persistent difficulties. The aim of this study was to examine the trajectory of psychiatric symptoms 1-6 months post-TBI, the patient/injury characteristics associated with changes, and characteristics predictive of persisting symptoms. ⋯ Significant predictors of caseness included African American race, age from 30 to 60 years, longer post-traumatic amnesia (PTA) duration, pre-TBI unemployment, and pre-TBI risky alcohol use. Findings indicate that psychiatric symptoms are common in the first 6 months post-TBI and frequently extend beyond the depression and anxiety symptoms that may be most commonly screened. Patients with longer PTA and preinjury alcohol misuse may need more intensive monitoring for symptom persistence.
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Journal of neurotrauma · Apr 2014
Case ReportsComprehensive Assessment of Isolated Traumatic Subarachnoid Hemorrhage.
Recent studies have shown that isolated traumatic subarachnoid hemorrhage (tSAH) in the setting of a high Glasgow Coma Scale (GCS) score (13-15) is a relatively less severe finding not likely to require operative neurosurgical intervention. This study sought to provide a more comprehensive assessment of isolated tSAH among patients with any GCS score, and to expand the analysis to examine the potential need for aggressive medical, endovascular, or open surgical interventions in these patients. By undertaking a retrospective review of all patients admitted to our trauma center from 2003-2012, we identified 661 patients with isolated tSAH. ⋯ There were six (1.7%) in-hospital deaths, and five patients of these patients were older than 80 years old. We conclude that isolated tSAH, regardless of admission GCS score, is a less severe intracranial injury that is highly unlikely to require aggressive operative, medical, or endovascular intervention, and is unlikely to be associated with major neurologic morbidity or mortality, except perhaps in elderly patients. Based upon our findings, we argue that impaired consciousness in the setting of isolated tSAH should strongly compel a consideration of non-traumatic factors in the etiology of the altered neurological status.