title: Role of the kallikrein-kinin system in traumatic brain injury.
abstract: Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Despite improvements in acute intensive care, there are currently no specific therapies to ameliorate the effects of TBI. Successful therapeutic strategies for TBI should target multiple pathophysiologic mechanisms that occur at different stages of brain injury. The kallikrein-kinin system is a promising therapeutic target for TBI as it mediates key pathologic events of traumatic brain damage, such as edema formation, inflammation, and thrombosis. Selective and specific kinin receptor antagonists and inhibitors of plasma kallikrein and coagulation factor XII have been developed, and have already shown therapeutic efficacy in animal models of stroke and TBI. However, conflicting preclinical evaluation, as well as limited and inconclusive data from clinical trials in TBI, suggests that caution should be taken before transferring observations made in animals to humans. This review summarizes current evidence on the pathologic significance of the kallikrein-kinin system during TBI in animal models and, where available, the experimental findings are compared with human data.
authors.affiliation: Department of Neurology, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Albert-Weissenberger
authors.affiliation: Department of Neurology, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Stine
authors.initials: S
authors.lastname: Mencl
authors.affiliation: Department of Neurology, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hopp
authors.affiliation: Department of Neurology, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Department of Neurosurgery, University Hospital of Würzburg Würzburg, Germany.
authors.forename: Anna-Leena
authors.initials: AL
authors.lastname: Sirén
keywords: bradykinin; factor XII; kallikrein–kinin system; kinin receptor; traumatic brain injury