Inflammasome Proteins as Biomarkers of Injury and Disease

The inflammasome is a multi-protein complex of the innate immune response that activates caspase-1 after infections, tissue injury, or disease. Once active caspase-1 cleaves the pro-inflammatory cytokines pro-IL-1β and pro-IL-18 into their respective mature forms, IL-1β and IL-18. Inflammasome proteins such as caspase-1, NOD-like receptor protein-1 (NLRP1), NLRP3, or apoptosis-associated speck-like protein containing a CARD (ASC) can be used as biomarkers of tissue injury and disease. For instance, higher levels of inflammasome proteins are present in the cerebrospinal fluid of patients with traumatic brain injury who present poor outcomes after trauma. Hence, the inflammasome after brain injury can be used as a tool to prognosticate outcomes after brain trauma. Similarly, in rodent models of multiple sclerosis, animals that do not respond to the classic interferon (IFN)-β treatment do not present an NLRP3 inflammasome-dependent disease. Thus, the inflammasome in multiple sclerosis can be used as a prognostic tool to identify responders to IFN-β treatment. In the same manner, patients taking finasteride for male pattern baldness who do not respond to treatment correlate with higher levels of caspase-1 in hair follicles. Moreover, the inflammasome can also be used as a biomarker of disease progression in diabetes and atherosclerosis, as well as a biomarker of tissue injury in inflammatory bowel disease and semen quality in patients with male infertility after spinal cord injury. Therefore, the inflammasome, a receptor of the innate immune response, is a useful biomarker in a variety of diseases and tissue injury

The evidence for hypothermia as a neuroprotectant in traumatic brain injury

This article reviews published experimental and clinical evidence for the benefits of modest hypothermia in the treatment of traumatic brain injury (TBI). Therapeutic hypothermia has been reported to improve outcome in several animal models of CNS injury and has been successfully translated to specific patient populations. A PubMed search for hypothermia and TBI was conducted, and important papers were selected for review. The research summarized was conducted at major academic institutions throughout the world. Experimental studies have emphasized that hypothermia can affect multiple pathophysiological mechanisms thought to participate in the detrimental consequences of TBI. Published data from several relevant clinical trials on the use of hypothermia in severely injured TBI patients are also reviewed. The consequences of mild to moderate levels of hypothermia introduced by different strategies to the head-injured patient for variable periods of time are discussed. Both experimental and clinical data support the beneficial effects of modest hypothermia following TBI in specific patient populations. Following on such single-institution studies, positive findings from multicenter TBI trials will be required before this experimental treatment can be considered standard of care