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Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury
Author(s) -
Luh Clara,
Kuhlmann Christoph R.,
Ackermann Bianca,
TimaruKast Ralph,
Luhmann Heiko J.,
Behl Christian,
Werner Christian,
Engelhard Kristin,
Thal Serge C.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06514.x
Subject(s) - myosin light chain kinase , edema , traumatic brain injury , blood–brain barrier , neuroprotection , medicine , phosphorylation , brain edema , myosin , lesion , cerebral edema , pathology , microbiology and biotechnology , central nervous system , biology , psychiatry
J. Neurochem. (2009) 112 , 1015–1025. Abstract The role of the endothelial contractile apparatus in the process of brain edema formation after brain trauma is not characterized. Phosphorylation of myosin light chains by myosin light chain kinases (MLCK) activates endothelial contractile elements and results in a rearrangement of the cytoskeleton. This may enhance post‐traumatic blood‐brain barrier dysfunction. In order to investigate the role of the MLCK on brain edema formation and blood‐brain barrier permeability after brain injury, mice were anesthetized and subjected to a controlled cortical impact (CCI). MLCK expression is significantly up‐regulated after CCI with a maximum 12 h post‐injury. Specific inhibition of MLCK by ML‐7 resulted in a reduction of phosphorylation of myosin light chains and improved blood‐brain‐barrier integrity. Accordingly, ML‐7 attenuated post‐traumatic brain edema formation and intracranial hypertension 24 h after CCI. Prevention of brain edema formation did not translate into improved neurological outcome or reduced brain lesion. In conclusion, the results confirm that the endothelial contractile apparatus is activated by CCI and opens the endothelial barrier leading to vasogenic brain edema formation. Lack of neurological and histological improvement suggests that specific targeting of vasogenic brain edema at the endothelial level is not sufficient to limit secondary brain damage and has, therefore, to be combined with other potential neuroprotective strategies.