Traumatic brain injury (TBI) may cause long-term disability. With increases in survival following initial injury, TBI can result in substantial and lifelong cognitive, physical, and behavioral impairments that require long-term health care and disability services. Common neurological sequelae occurring after TBI includes epilepsy or neurodegenerative diseases (stroke, Alzheimer’s disease or Parkinson’s disease). Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are associated with an inflammatory response of the lung. The development of ALI/ARDS in patients with TBI is a great challenge for clinicians. While the mechanism how TBI induces ALI remains unclear, there are studies indicating that ALI after TBI is usually due to stress responses or sympathetic storm, acute systematic inflammation, pulmonary edema or pneumonia. The activation of multiple types of inflammatory cells and the release of a series of inflammatory mediators (cytokines and chemokines) causes secondary brain damage. The activation of more inflammatory cells and the release of more inflammatory mediators amplifies the injury, resulting in systemic inflammation, where lung is the most susceptible organ among others. The central hypothesis of this project is that TBI-induced pulmonary damage (second hit) which worsens the pulmonary function and leads to hypoxia, causing more severe damage to the brain (third hit) and thus results in more severe neurological sequelae or even early onset neurodegenerative diseases. This project aims to investigate the correlation between TBI and ALI/ARDS, and to study the mechanism of “second hit” and “third hit”. We will also treat the TBI animals with drugs that we previously proved therapeutic effect in TBI to evaluate the effectiveness of these drugs on TBI-induced ALI. Using a rat model of TBI (injured by control cortical impact), we have previously found elevated concentrations of CXCL chemokines (the chemotracttant cytokines such as MIP-2, or CINC-3) that specifically attract neutrophils, in serum and CSF. In the first year (2015-16), we will investigate whether the degree of TBI-induced ALI is related to degree of brain injury and whether brain inflammation or systemic inflammation is related to pathogenesis of TBI- induced ALI. In the second year, we will check whether TBI induced damage molecules, up-regulated TLRs and their downstream molecules are related to pathogenesis of TBI induced ALI. In the third year, we will check whether rat brain specific miRNA, miR-222 is related to TBI induced secondary brain injury and whether a miRNA is related to TBI induced ALI. Key words: Traumatic brain injury (TBI), neurological sequalae, acute lung injury, cytokines, chemokine/receptors, s100B/RAGE, health insurance database
|Effective start/end date
|8/1/16 → 7/31/17
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