Systemic Inflammation After Brain Injuries - A Potential Target for Concussion Treatments?

Who is going to see if something like this should be researched for strokes/TBIs?
http://sportsmedresearch.blogspot.com/2011/12/systemic-inflammation-after-brain.html

Traumatic brain injury (TBI) induces an immune response that includes the release of inflammatory mediators (e.g., CCL20) and infiltration of white blood cells into the brain. The spleen is a reservoir of immune cells and plays an important role in systemic immune responses. Identifying specific inflammatory mediators involved in the progression of TBI pathology may help identify a key pathway for therapeutic interventions. Therefore, the purpose of this study was to examine the relationship between the brain’s response to TBI and the systematic immune reaction in a rat model of TBI. Thirty-three rats were concussed utilizing a lateral fluid percussion injury (the link provides video of how the injury was induced [includes surgical footage]). In control animals, the surgery was performed but the lateral fluid percussion injury was not induced. Some animals also had their spleens removed (splenectomy) at the time of the brain injury. One or 2 days after the concussion, the investigators evaluated the thymus, brain, and spleen (in animals where the spleen was not removed). These time points were chosen because they represent a key time during the secondary injury phase when therapuetic agents could block the secondary inflammatory process or promote repair mechanisms. Gene expression of inflammatory mediators (and their receptors) as well as tissue concentrations of CCL20 were evaluated in tissue samples from the spleens. The brain tissues were assessed for signs of degenerating neurons and cell death (apoptosis). The presence of CCL20 protein was also evaluated in the spleen, thymus, and brain tissue using microscopy. The authors found significant amounts of injured neurons within the cerebral cortex, hippocampus, and thalamus both 1 and 2 days after injury compared to the control animals (did not receive concussion injury). There were signs of cell death within the cortex (same side as the impact) and hippocampus at 1 day after the injury but not 2 days after injury compared to the control animals. CCL20 gene expression and protein concentrations were increased in the spleen and thymus 1 day after injury. In contrast, CCL20 was not detected in the brain until 2 days after the injury. Degeneration of neurons were seen in both splenectomy and non-splenectomy rats 1 and 2 days post injury but the splenectomy animals had less neuron degeneration than the animals who still had a spleen. Two days after the injury there were higher levels of CCL20 expression in the brain of animals that still had a spleen compared to splenectomy animals.

This study is important because it demonstrates that there is a systemic inflammatory response to some concussions that can promote secondary brain inflammation and promote neurodegeneration. When the spleen was removed in these animals it reduced the amount of neuron degeneration and the expression of inflammatory mediators in the brain. The authors state “The fact that CCL20 expression is elevated in the spleen and thymus prior to its appearance in the brain, and that brain CCL20 expression is decreased in splenectomised rats provide evidence that a peripheral CCL20 signal mediates the neuropathological response to TBI.” Further investigation are required to determine the mechanism by which CCL20 signals neuron death as well as the exact roles of the spleen and thymus contribute to neuron death. This also supports the idea that after concussions, like many other injuries, it may be important for us to find methods of reducing secondary phases of cell injury. Do you think having a therapeutic agent would change the return to play time of your athlete? Or, would it just assist in alleviating some of the potential secondary effects of a concussion?