ABSTRACT
Mild traumatic brain injury (mTBI), particularly mild "blast type" injuries resulting from improvised exploding devices and many sport-caused injuries to the brain, result in long-term impairment of cognition and behavior. Our central hypothesis is that there are inflammatory consequences to mTBI that persist over time and, in part, are responsible for resultant pathogenesis and clinical outcomes. We used an adaptation (1 atmosphere pressure) of a well-characterized moderate-to-severe brain lateral fluid percussion (LFP) brain injury rat model. Our mild LFP injury resulted in acute increases in interleukin-1α/ß and tumor necrosis factor alpha levels, macrophage/microglial and astrocytic activation, evidence of heightened cellular stress, and blood-brain barrier (BBB) dysfunction that were evident as early as 3-6 h postinjury. Both glial activation and BBB dysfunction persisted for 18 days postinjury.
Subject(s)
Brain Concussion/pathology , Inflammation/pathology , Animals , Blood-Brain Barrier/pathology , Brain/pathology , Brain Concussion/complications , Cytokines/analysis , Cytokines/biosynthesis , Disease Models, Animal , Immunoassay , Inflammation/etiology , Male , Microscopy, Confocal , Motor Activity/physiology , Rats , Rats, Sprague-DawleyABSTRACT
Exposure to hypoxia and hyperoxia in a rodent model of perinatal ischemia results in delayed cell death and inflammation. Hyperoxia increases oxidative stress that can trigger inflammatory cascades, neutrophil activation, and brain microvascular injury. Here we show that 100% oxygen resuscitation in our rodent model of perinatal ischemia increases cortical COX-2 protein levels, S-nitrosylated COX-2cys526, PGE2, iNOS and 5-LOX, all components of the prostaglandin and leukotriene inflammatory pathway.
