Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier.

摘要: Traumatic brain injury (TBI) is the leading cause of death and disability in young Americans, with 1.7 million cases occurring yearly.1 In severe TBI, intracranial hypertension occurs when swells against noncom-pliant dura and, if uncontrolled, may herniation ultimately death. Brain edema after TBI occur through a leaky blood-brain barrier (BBB) resulting from initial impact but also ongoing cerebrovascular inflammation injury.2 Although several neuroprotective therapies have shown promise animal studies, none been successful clinically, to date no therapy exists curb progression cerebral trauma. In last decade, increasing evidence has emerged, suggesting that polymorphonuclear neutrophil (PMN) endothelial cell (EC) activation microcirculation sustain persistent microvascular disruption evolves hours injury.1,2 systemic circulation, PMNs pass vasculature tissue series steps involving surface adhesion receptors on both PMN EC result reaching site perform cytotoxic phagocytic functions.3 some cases, neutrophils become inappropriately activated release substances intravascularly, vascular organ injury.4 Decreasing this inflammatory host response at BBB potentially decrease secondary improve clinical outcomes. Progesterone (PRO), potent sex neurosteroid, survival cognitive recovery currently being investigated phase 3 trial.5,6 Known effects PRO include neuronal apoptosis blunting oxygen-free radical cytokine production.5 It remains unknown whether affects circulating ECs how relates injury. We hypothesized visibly reduces EC/PMN interaction microcirculation, decreases edema, results greater functional murine model.