Abstract:

Traumatic brain injury (TBI) is a serious pathology affecting around 10 million people annually, being a persistent public health and medical problem. Although TBI has long term consequences due to the immediate loss of brain tissue, treatment has focused on mitigating secondary damage. Yet there exist more that 30 clinical trials for TBI that fail despite successful experimental data. Most of these studies were based on neuroprotective treatments to reduce inflammation and neurodegeneration in the injured brain, with consequent the motor and cognitive improvements. However, injury to the brain also produces alterations in the bloodstream and peripheral organs. Recent breakthroughs in brain injury research investigate the link between brain inflammation and peripheral organs; and one of the most sensitive organs to inflammation is the liver. The systemic production of cytokines and chemokines by the liver and other organs, in response to the brain damage, is an essential factor of the inflammatory secondary response in the brain due to communication of brain-periphery. Recent studies have demonstrated that focal injury to the brain elicits a rapid hepatic response, the production of chemokines by the liver acts as an amplifier of the focal injury response providing a route of CNS-liver communication. The blockade of inflammatory intermediaries of the liver after brain injury can effectively alter the recruitment of leukocytes to the brain, an important factor to consider when peripheral inflammation exacerbates the progression of brain damage. As an acute phase protein with pleiotropic pro-inflammatory properties, SAA may represent an important link between brain injury and hepatic and systemic inflammation. Yet, there is also evidence to suggest that systemic inflammation confers a degree of tolerance to brain injury. Like the liver, other secondary organs damaged by similar pathologies observed in patients with acute brain injury may also represent alternative therapeutic targets for improving clinical outcome. In conclusion, since inflammation appears to be a common link between brain injury and the periphery, one is led to hypothesize that inflammatory signals released after TBI could regulate components of hepatic response and that consequently induce detrimental changes damaged brain regions.