Cargando…

Role of the kallikrein–kinin system in traumatic brain injury

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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: Albert-Weissenberger, Christiane, Mencl, Stine, Hopp, Sarah, Kleinschnitz, Christoph, Sirén, Anna-Leena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217500/
https://www.ncbi.nlm.nih.gov/pubmed/25404891
http://dx.doi.org/10.3389/fncel.2014.00345
_version_ 1782342397867327488
author Albert-Weissenberger, Christiane
Mencl, Stine
Hopp, Sarah
Kleinschnitz, Christoph
Sirén, Anna-Leena
author_facet Albert-Weissenberger, Christiane
Mencl, Stine
Hopp, Sarah
Kleinschnitz, Christoph
Sirén, Anna-Leena
author_sort Albert-Weissenberger, Christiane
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4217500
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-42175002014-11-17 Role of the kallikrein–kinin system in traumatic brain injury Albert-Weissenberger, Christiane Mencl, Stine Hopp, Sarah Kleinschnitz, Christoph Sirén, Anna-Leena Front Cell Neurosci Neuroscience 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. Frontiers Media S.A. 2014-11-03 /pmc/articles/PMC4217500/ /pubmed/25404891 http://dx.doi.org/10.3389/fncel.2014.00345 Text en Copyright © 2014 Albert-Weissenberger, Mencl, Hopp, Kleinschnitz and Sirén. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Albert-Weissenberger, Christiane
Mencl, Stine
Hopp, Sarah
Kleinschnitz, Christoph
Sirén, Anna-Leena
Role of the kallikrein–kinin system in traumatic brain injury
title Role of the kallikrein–kinin system in traumatic brain injury
title_full Role of the kallikrein–kinin system in traumatic brain injury
title_fullStr Role of the kallikrein–kinin system in traumatic brain injury
title_full_unstemmed Role of the kallikrein–kinin system in traumatic brain injury
title_short Role of the kallikrein–kinin system in traumatic brain injury
title_sort role of the kallikrein–kinin system in traumatic brain injury
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217500/
https://www.ncbi.nlm.nih.gov/pubmed/25404891
http://dx.doi.org/10.3389/fncel.2014.00345
work_keys_str_mv AT albertweissenbergerchristiane roleofthekallikreinkininsystemintraumaticbraininjury
AT menclstine roleofthekallikreinkininsystemintraumaticbraininjury
AT hoppsarah roleofthekallikreinkininsystemintraumaticbraininjury
AT kleinschnitzchristoph roleofthekallikreinkininsystemintraumaticbraininjury
AT sirenannaleena roleofthekallikreinkininsystemintraumaticbraininjury