Articles: traumatic-brain-injuries.
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The Brain Trauma Foundation has published guidelines on the surgical management of traumatic subdural hematoma (SDH). However, no data exist on the proportion of patients with SDH that can be selected for conservative management and what is the outcome of these patients. The goals of this study were as follows: 1) to establish what proportion of patients are initially treated conservatively; 2) to determine what proportion of patients will deteriorate and require surgical evacuation; and 3) to identify risk factors associated with deterioration and delayed surgery. ⋯ The majority of patients with SDH are treated conservatively. Of those, only 6.5% later required surgery, for raised intracranial pressure or SDH progression. Patients at risk can be identified and followed more carefully.
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Despite pediatric guidelines, variability exists in the management of severe traumatic brain injury (TBI), as somewhere between 7 and 60% of children undergo intracranial pressure (ICP) monitoring. Reasons for this low adherence to TBI management guidelines remain unclear. The objective of this study was to evaluate the current practices at CHU Sainte-Justine with regards to ICP monitoring in severe TBI and explore the reasons why ICP monitoring is not undertaken. ⋯ Our study confirms that many children with severe TBI do not undergo ICP monitoring, mainly due to rapid improvement or moribund status. A subgroup of patients, with reassuring cerebral CT scan, was not monitored. Further research is necessary to assess if imaging should be considered in ICP indication, as in adult guidelines.
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Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Dawley rats of 2-3 months of age (128 CCI-injured and 28 controls) was used for monitoring and/or anatomical studies. ⋯ CCI caused severe brain tissue loss and cavitation of the ipsilateral cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3 regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI-injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the inner molecular layer. These results indicate that the CCI model of TBI in adult rats can be used to study the structure-function relationships that underlie epileptogenesis and PTE.
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The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. ⋯ Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures.
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SB-3CT is a potent and selective inhibitor of matrix metalloproteinase (MMP)-2 and -9, which has shown efficacy in an animal model of severe traumatic brain injury (TBI). However, SB-3CT is poorly water-soluble and is metabolized primarily to p-hydroxy SB-3CT (2), a more potent inhibitor than SB-3CT. We synthesized the O-phosphate prodrug (3) of compound 2 to enhance its water solubility by more than 2000-fold. ⋯ Pharmacokinetics and brain distribution studies in mice showed that 2 crossed the blood-brain barrier (BBB) and achieved therapeutic concentrations in the brain. The prodrug 3/compound 2 was evaluated in a mouse model of severe TBI and found to significantly decrease the brain lesion volume and improve neurological outcomes. MMP-9 inhibition by a water-soluble thiirane inhibitor is a promising therapy for treatment of TBI.