Journal of neurotrauma
-
Journal of neurotrauma · Jul 2010
Genetic deletion and pharmacological inhibition of Nogo-66 receptor impairs cognitive outcome after traumatic brain injury in mice.
Functional recovery is markedly restricted following traumatic brain injury (TBI), partly due to myelin-associated inhibitors including Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), that all bind to the Nogo-66 receptor-1 (NgR1). In previous studies, pharmacological neutralization of both Nogo-A and MAG improved outcome following TBI in the rat, and neutralization of NgR1 improved outcome following spinal cord injury and stroke in rodent models. However, the behavioral and histological effects of NgR1 inhibition have not previously been evaluated in TBI. ⋯ In the sNgR1 study, we evaluated hippocampal mossy fiber sprouting using the Timm stain and found it to be increased at 5 weeks following TBI. Neutralization of NgR1 significantly increased mossy fiber sprouting in sham-injured animals, but not in brain-injured animals. Our data suggest a complex role for myelin-associated inhibitors in the behavioral recovery process following TBI, and urge caution when inhibiting NgR1 in the early post-injury period.
-
Journal of neurotrauma · Jul 2010
Quality of Life after Brain Injury (QOLIBRI): scale development and metric properties.
The consequences of traumatic brain injury (TBI) for health-related quality of life (HRQoL) are poorly investigated, and a TBI-specific instrument has not previously been available. The cross-cultural development of a new measure to assess HRQoL after TBI is described here. An international TBI Task Force derived a conceptual model from previous work, constructed an initial item bank of 148 items, and then reduced the item set through two successive multicenter validation studies. ⋯ Although there is one strong HRQoL factor, a six-scale structure explaining additional variance was validated by exploratory and confirmatory factor analyses, and with Rasch modeling. The QOLIBRI is a new cross-culturally developed instrument for assessing HRQoL after TBI that fulfills standard psychometric criteria. It is potentially useful for clinicians and researchers conducting clinical trials, for assessing the impact of rehabilitation or other interventions, and for carrying out epidemiological surveys.
-
Journal of neurotrauma · Jul 2010
Minozac treatment prevents increased seizure susceptibility in a mouse "two-hit" model of closed skull traumatic brain injury and electroconvulsive shock-induced seizures.
The mechanisms linking traumatic brain injury (TBI) to post-traumatic epilepsy (PTE) are not known and no therapy for prevention of PTE is available. We used a mouse closed-skull midline impact model to test the hypotheses that TBI increases susceptibility to seizures in a "two-hit" injury model, and that suppression of cytokine upregulation after the first hit will attenuate the increased susceptibility to the second neurological insult. Adult male CD-1 mice underwent midline closed skull pneumatic impact. ⋯ Astrocyte activation, metallothionein expression, and neurobehavioral impairment were also increased in the two-hit group subjected to combined TBI and ECS. These enhanced responses in the two-hit group were also prevented by suppression of proinflammatory cytokine upregulation with Mzc. These data implicate glial activation in the mechanisms of epileptogenesis after TBI, and identify a potential therapeutic approach to attenuate the delayed neurological sequelae of TBI.
-
Journal of neurotrauma · Jul 2010
Comparative StudyObserved versus predicted outcome for decompressive craniectomy: a population-based study.
A number of studies have shown that decompressive craniectomy can reduce intracranial pressure and may improve outcome for patients with severe head injury. This cohort study assessed the long-term outcome of neurotrauma patients who had a decompressive craniectomy for severe head injury in Western Australia between 2004 and 2008. The web-based outcome prediction model developed by the CRASH trial collaborators was applied to the cohort. ⋯ The functional outcome after either unilateral or bilateral decompressive craniectomy was significantly better than that predicted by the CRASH head injury prediction model when the predicted risk was less than 80%. This study has demonstrated that in Western Australia decompressive craniectomy is a relatively common surgical procedure for the management of neurotrauma. A significant proportion of patients had a better-than-predicted long-term functional outcome.
-
Journal of neurotrauma · Jul 2010
Inappropriate prehospital ventilation in severe traumatic brain injury increases in-hospital mortality.
In the setting of acute brainstem herniation in traumatic brain injury (TBI), the use of hyperventilation to reduce intracranial pressure may be life-saving. However, undue use of hyperventilation is thought to increase the incidence of secondary brain injury through direct reduction of cerebral blood flow. This is a retrospective review determining the effect of prehospital hyperventilation on in-hospital mortality following severe TBI. ⋯ Although there are many reports of the negative impact of prophylactic hyperventilation following severe TBI, this modality is frequently utilized in the prehospital setting. Our results suggest that abnormal Pco(2) on presentation after severe head trauma is correlated with increased in-hospital mortality. We advocate normoventilation in the prehospital setting.