XXXX and neuroprotection in traumatic brain injury.

@entity1 @entity32 @entity131 @entity1545 @entity26 @entity51 @entity460 @entity204 @entity130
IMPORTANCE: Traumatic brain injury ( @entity131 ) is a significant public health concern that affects individuals in all demographics. With increasing interest in the medical and public communities, understanding the inflammatory mechanisms that drive the pathologic and consequent cognitive outcomes can inform future research and clinical decisions for @entity1 with @entity131 . OBJECTIVES: To review known inflammatory mechanisms in @entity131 and to highlight clinical trials and neuroprotective therapeutic manipulations of pathologic and inflammatory mechanisms of @entity131 . EVIDENCE REVIEW: We searched articles in PubMed published between 1960 and August 1, 2014, using the following keywords: traumatic @entity1545 , @entity130 , @entity32 , astrocytes, microglia, monocytes, macrophages, neutrophils, T cells, reactive @entity26 species, alarmins, danger-associated molecular patterns, purinergic receptors, neuroprotection, and clinical trials. Previous clinical trials or therapeutic studies that involved manipulation of the discussed mechanisms were considered for inclusion. The final list of selected studies was assembled based on novelty and direct relevance to the primary focus of this review. FINDINGS: Traumatic brain injury is a diverse group of sterile injuries induced by primary and secondary mechanisms that give rise to cell @entity204 , @entity32 , and @entity51 in @entity1 of all demographics. Pathogenesis is driven by complex, interacting mechanisms that include reactive @entity26 species, ion channel and gap junction signaling, purinergic receptor signaling, excitotoxic neurotransmitter signaling, perturbations in @entity460 homeostasis, and damage-associated molecular pattern molecules, among others. Central nervous system resident and peripherally derived inflammatory cells respond to @entity131 and can provide neuroprotection or participate in @entity130 reactions. The exact contribution of inflammatory cells to a @entity131 is dictated by their anatomical positioning as well as the local cues to which they are exposed. CONCLUSIONS AND RELEVANCE: The mechanisms that drive @entity131 development as well as those that promote repair are exceedingly complex and often superimposed. Because pathogenic mechanisms can diversify over time or even differ based on the @entity130 , it is important that neuroprotective therapeutics be developed and administered with these variables in mind. Due to its complexity, @entity131 has proven particularly challenging to treat; however, a number of promising therapeutic approaches are now under pre-clinical development, and recent clinical trials have even yielded a few successes. Given the worldwide impact of @entity131 on the @entity1 population, it is imperative that research remains active in this area and that we continue to develop therapeutics to improve outcome in afflicted @entity1 .
