title: The blood-brain barrier as a target in traumatic brain injury treatment.
abstract: Traumatic brain injury (TBI) is one of the most frequent causes of death in the young population. Several clinical trials have unsuccessfully focused on direct neuroprotective therapies. Recently immunotherapeutic strategies shifted into focus of translational research in acute CNS diseases. Cross-talk between activated microglia and blood-brain barrier (BBB) could initiate opening of the BBB and subsequent recruitment of systemic immune cells and mediators into the brain. Stabilization of the BBB after TBI could be a promising strategy to limit neuronal inflammation, secondary brain damage and acute neurodegeneration. This review provides an overview on the pathophysiology of TBI and brain edema formation including definitions and classification of TBI, current clinical treatment strategies, as well as current understanding on the underlying cellular processes. A summary of in vivo and in vitro models to study different aspects of TBI is presented. Three mechanisms proposed for stabilization of the BBB, myosin light chain kinases, glucocorticoid receptors and peroxisome proliferator-activated receptors are reviewed for their influence on barrier-integrity and outcome after TBI. In conclusion, the BBB is recommended as a promising target for the treatment of traumatic brain injury, and it is suggested that a combination of BBB stabilization and neuroprotectants may improve therapeutic success.
authors.affiliation: Department of Anesthesia and Critical Care, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Serge C
authors.initials: SC
authors.lastname: Thal
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse, Vienna, Austria; Department of Anesthesia and Critical Care, University Hospital Wuerzburg, Wuerzburg, Germany. Electronic address: winfried.neuhaus@univie.ac.at.
authors.forename: Winfried
authors.initials: W
authors.lastname: Neuhaus
mesh_terms: D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy*; D015687:Cell Hypoxia / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000378:metabolism; D000077205:Pioglitazone; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D047492:Peroxisome Proliferator-Activated Receptors; D011965:Receptors, Glucocorticoid; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009219:Myosin-Light-Chain Kinase; D000077205:Pioglitazone
keywords: Blood–brain barrier; Brain injury; Immune cells; Neuronal inflammation