Pharmacologic management of brain edema
ABSTRACT Cerebral edema is an intrinsic response to a variety of structural and metabolic insults. It is a major contributing factor in the development of intracranial hypertension and brain herniation, underscoring the need for early identification through an integration of clinical and neuroimaging findings, followed by timely institution of measures to reduce brain edema and intracranial hypertension. The management of cerebral edema requires a comprehensive approach in which pharmacologic treatments play a central role. These include glucocorticoids, hyperosmolar agents, diuretics, and sedative-anesthetic agents. Basic, translational, and clinical studies are needed to further unravel mechanisms underlying brain edema, with the goal of identifying new treatment strategies. Promising targets include modulators of endothelial cell tight junction proteins and of aquaporin channel expression within the blood-brain barrier.
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ABSTRACT: AQP3 is a water/glycerol transporter expressed at the basolateral membrane of colonic epithelial cells. Although AQPs are expressed in the gastrointestinal tract, their effect on intestinal barrier has not been clear. Here, we showed that knockdown of AQP3 caused a dramatic, dose-dependent increase in E. coli C25 translocation, with the reduction of TEER and increasing LY permeability. Western blots revealed that expression of Claudin-1 and Occludin were significantly decreased in the AQP3 knockdown group, demonstrating that this treatment enhances paracellular permeability via an opening of the tight junction complex. These data not only describe the correlation between transcellular and paracellular pathways in human intestines, but also show that targeted knockdown of AQP3 might impair the intestinal barrier integrity.FEBS letters 09/2011; 585(19):3113-9. DOI:10.1016/j.febslet.2011.08.045 · 3.34 Impact Factor
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ABSTRACT: Worldwide, severe traumatic brain injury is a frequent pathology and is associated with high morbidity and mortality. Mannitol and hypertonic saline are therapeutic options for intracranial hypertension occurring in the acute phase of care. However, current practices of emergency physicians are unknown. We conducted a self-administered survey of emergency physicians in the province of Québec, Canada, to understand their attitudes surrounding the use of hyperosmolar solutions in patients with severe traumatic brain injury. Using information from a systematic review of hypertonic saline solutions and experts' opinion, we developed a questionnaire following a systematic approach (items generation and reduction). We tested the questionnaire for face and content validity, and test-retest reliability. Physicians were identified through the department head of each eligible level I and II trauma centers. We administered the survey using a web-based interface and planned email reminders. We received 210 questionnaires out of 429 potentials respondents (response rate 49%). Most respondents worked in level II trauma centers (69%). Fifty-three percent (53%) of emergency physicians stated using hypertonic saline to treat severe traumatic brain injury. Most reported using hyperosmolar therapy in the presence of severe traumatic brain injury and unilateral reactive mydriasis, midline shift or cistern compression on brain computed tomography. Hyperosmolar therapy is believed being broadly used by emergency physicians in Quebec following severe traumatic brain injury. Despite the absence of clinical practice guidelines promoting the use of hypertonic saline, a majority of them said to use these solutions in specific clinical situations.PLoS ONE 04/2014; 9(4):e95778. DOI:10.1371/journal.pone.0095778 · 3.53 Impact Factor