Journal of neurotrauma
-
Journal of neurotrauma · May 2010
Multicenter StudyA method for reducing misclassification in the extended Glasgow Outcome Score.
The eight-point extended Glasgow Outcome Scale (GOSE) is commonly used as the primary outcome measure in traumatic brain injury (TBI) clinical trials. The outcome is conventionally collected through a structured interview with the patient alone or together with a caretaker. Despite the fact that using the structured interview questionnaires helps reach agreement in GOSE assessment between raters, significant variation remains among different raters. ⋯ The group using the alternative rating system coupled with central monitoring yielded the highest inter-rater agreement among the three groups in rating GOS (97%; weighted kappa = 0.95; 95% CI 0.89, 1.00), and GOSE (97%; weighted kappa = 0.97; 95% CI 0.91, 1.00). The alternate system is an improved GOSE rating method that reduces inter-rater variations and provides for the first time, source documentation and structured narratives that allow a thorough central review of information. The data suggest that a collective effort can be made to minimize inter-rater variation.
-
Journal of neurotrauma · May 2010
Diffuse brain injury elevates tonic glutamate levels and potassium-evoked glutamate release in discrete brain regions at two days post-injury: an enzyme-based microelectrode array study.
Traumatic brain injury (TBI) survivors often suffer from a wide range of post-traumatic deficits, including impairments in behavioral, cognitive, and motor function. Regulation of glutamate signaling is vital for proper neuronal excitation in the central nervous system. Without proper regulation, increases in extracellular glutamate can contribute to the pathophysiology and neurological dysfunction seen in TBI. ⋯ The amplitudes of KCl-evoked glutamate release were increased significantly only in the striatum after moderate injury, with a 249% increase seen in the dorsal striatum. Thus, with the MEAs, we measured discrete regional changes in both tonic and KCl-evoked glutamate signaling, which were dependent on injury severity. Future studies may reveal the specific mechanisms responsible for glutamate dysregulation in the post-traumatic period, and may provide novel therapeutic means to improve outcomes after TBI.
-
Journal of neurotrauma · May 2010
Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelve-week follow-up study.
Traumatic brain injury (TBI) causes a wide spectrum of consequences, such as microglial activation, cerebral inflammation, and focal and diffuse brain injury, as well as functional impairment. In this study we aimed to investigate the effects of acute treatment with minocycline as an inhibitor of microglial activation on cerebral focal and diffuse lesions, and on the spontaneous locomotor activity following TBI. The weight-drop model was used to induce TBI in mice. ⋯ More interestingly, minocycline significantly decreased TBI-induced locomotor hyperactivity at 48 h post-TBI, and its effect lasted for up to 8 weeks. Taken together, the results indicate that microglial activation appears to play an important role in the development of TBI-induced focal injury and the subsequent locomotor hyperactivity, and its short-term inhibition provides long-lasting functional recovery after TBI. These findings emphasize the fact that minocycline could be a promising new therapeutic strategy for head-injured patients.
-
Journal of neurotrauma · May 2010
Finite element analysis of controlled cortical impact-induced cell loss.
The controlled cortical impact (CCI) model has been extensively used to study region-specific patterns of neuronal injury and cell death after a focal traumatic brain injury. Although external parameters such as impact velocity and depth of penetration have been defined in this injury model, little is known about the intracranial mechanical responses within cortical and subcortical brain regions where neuronal loss is prevalent. At present, one of the best methods to determine the internal responses of the brain is finite element (FE) modeling. ⋯ A linear relationship was found between the percentage of the neuronal loss observed in vivo and the FE model-predicted maximum principal strain (R(2) = 0.602). Interestingly, the FE model also predicted some risk of injury in the cerebellum, located remote from the point of impact, with a 25% neuronal loss for the "severe" impact condition. More research is needed to examine other regions that do not have histological data for comparison with FE model predictions before this injury mechanism and the associated injury threshold can be fully established.
-
Journal of neurotrauma · May 2010
Prokineticin 2 expression is associated with neural repair of injured adult zebrafish telencephalon.
Prokineticin 2 (PROK2) is a secreted protein that regulates diverse biological processes including olfactory bulb neurogenesis in adult mammals. However, its precise role in this process is as yet not fully understood. Because it is well known that adult teleost fish, including zebrafish, display an intense proliferative activity in several brain regions, we took advantage of this feature to analyze the distribution of PROK2 transcripts in the adult zebrafish brain and during injury-induced telencephalon (TC) regeneration. ⋯ In addition, we observed a transient over-expression of PROK2 transcripts, which was detected in cells surrounding the lesion during the very first days post injury, and, a few days later, in broad cell rows extending from cortical regions of the TC toward injury sites. PROK2 over-expression was no longer detected when the regeneration process was close to completion, showing that ectopic PROK2 transcription paralleled neuronal regeneration. Taken together, our results suggest that in adult zebrafish brain, PROK2 may play a role in both constitutive and injury-induced neurogenesis.