Journal of neurotrauma
-
Journal of neurotrauma · Jan 2012
Mechanisms of dendritic spine remodeling in a rat model of traumatic brain injury.
Traumatic brain injury (TBI), a leading cause of death and disability in the United States, causes potentially preventable damage in part through the dysregulation of neural calcium levels. Calcium dysregulation could affect the activity of the calcium-sensitive phosphatase calcineurin (CaN), with serious implications for neural function. The present study used both an in vitro enzymatic assay and Western blot analyses to characterize the effects of lateral fluid percussion injury on CaN activity and CaN-dependent signaling in the rat forebrain. ⋯ These changes occurred bilaterally in the neocortex and hippocampus, appeared to persist for hours after injury, and coincided with synapse degeneration, as suggested by a loss of the excitatory post-synaptic protein PSD-95. Interestingly, the effect of TBI on cofilin in some brain regions was blocked by a single bolus of the CaN inhibitor FK506, given 1 h post-TBI. Overall, these findings suggest a loss of synapse stability in both hemispheres of the laterally-injured brain, and offer evidence for region-specific, CaN-dependent mechanisms.
-
Journal of neurotrauma · Jan 2012
Failure of delayed intravenous administration of bone marrow stromal cells after traumatic brain injury.
Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Currently, there is no effective strategy to treat the functional sequelae associated with TBI. Experimental evidence shows that the intravenous administration of bone marrow stromal cells (BMSC) during the first week after TBI prevents neurological deficits, but no experimental studies have shown evidence of the effect of intravenous BMSC on chronic brain injury sequelae. ⋯ At the end of the study period the animals were sacrificed and their brains were studied to evaluate possible differences between groups. Two months after BMSC administration no significant differences were detected in the motor and sensory evaluation between animals treated with BMSC and controls, and no differences were detected after histological study of the brains. Our present results suggest that intravenous administration of BMSC after TBI, when the neurological deficits are well established, has no beneficial effect in neurological outcomes or on brain tissue.
-
Journal of neurotrauma · Jan 2012
Cell-free DNA as a marker for prediction of brain damage in traumatic brain injury in rats.
Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and early predictors of neurological outcomes are of great clinical importance. Cell free DNA (CFD), a biomarker used for the diagnosis and monitoring of several diseases, has been implicated as a possible prognostic indicator after TBI. The purpose of this study was to determine the pattern and timing of CFD levels after TBI, and whether a relationship exists between the level of CFD and brain edema and neurological outcomes. ⋯ In this study, we demonstrated an increase in CFD levels after TBI, as well as a correlation between CFD levels and brain edema and NSS. CFD levels may provide a quick, reliable, and simple prognostic indicator of neurological outcome in animals after TBI. Its role in humans has not been clearly elucidated, but has potentially significant clinical implications.
-
Journal of neurotrauma · Jan 2012
ReviewEfficacy and safety of dopamine agonists in traumatic brain injury: a systematic review of randomized controlled trials.
In the intensive care unit, dopamine agonists (DA) have been used in traumatic brain injury (TBI) patients to augment or accelerate cognitive recovery and rehabilitation. However, the efficacy and safety of DA in this population is not well established. We conducted a systematic review of randomized controlled trials (RCTs) examining the clinical efficacy and safety of DA in patients with TBI. ⋯ No trend could be drawn from the analysis of efficacy and safety. Important sources of bias in the studies were of major concern. Considering the absence of consensus regarding clinical outcome, the lack of safety assessment, and the high risk of bias in the included trials, more research is warranted before DA can be recommended in critically ill TBI patients.
-
Journal of neurotrauma · Jan 2012
Multicenter StudyMulticenter evaluation of the course of coagulopathy in patients with isolated traumatic brain injury: relation to CT characteristics and outcome.
This prospective multicenter study investigated the association of the course of coagulation abnormalities with initial computed tomography (CT) characteristics and outcome in patients with isolated traumatic brain injury (TBI). Patient demographics, coagulation parameters, CT characteristics, and outcome data of moderate and severe TBI patients without major extracranial injuries were prospectively collected. Coagulopathy was defined as absent, early but temporary, delayed, or early and sustained. ⋯ The relative risk for in-hospital mortality was particularly related to disturbed pupillary responses (OR 8.19; 95% CI 3.15,21.32; p<0.001), early, short-lasting coagulopathy (OR 6.70; 95% CI 1.74,25.78; p=0.006), or delayed/sustained coagulopathy (OR 5.25; 95% CI 2.06,13.40; p=0.001). Delayed/sustained coagulopathy is more frequently associated with CT abnormalities and unfavorable outcome at 6 months after TBI than early, short-lasting coagulopathy. Our finding that not only the mere presence but also the time course of coagulopathy holds predictive value for patient outcome underlines the importance of systematic hemostatic monitoring over time in TBI.