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Traumatic brain injury impairs myogenic constriction of cerebral arteries: role of mitochondria‐derived H 2 O 2 , TRPV4 and calcium‐activated potassium channels
Author(s) -
Szarka Nikolett,
Pabbidi Mallikarjuna R.,
Amrein Krisztina,
Czeiter Endre,
Pohoczky Krisztina,
Helyes Zsuzsanna,
Ungvari Zoltan,
Buki Andras,
Koller Akos,
Toth Peter J
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.836.5
Subject(s) - trpv4 , traumatic brain injury , transient receptor potential channel , potassium channel , mitochondrion , oxidative stress , medicine , cerebral arteries , anesthesia , neuroscience , chemistry , endocrinology , biology , receptor , biochemistry , psychiatry
Traumatic brain injury (TBI) impairs pressure‐induced myogenic constriction of cerebral arteries, which contributes to TBI‐related autoregulatory dysfunction and the development of secondary brain injury. TBI has been shown to lead to mitochondrial oxidative stress in cerebral vessels, which likely contributes to secondary brain injury, as well. We tested the hypothesis that TBI‐induced mitochondrial oxidative stress contributes to the impaired myogenic response of cerebral arteries after TBI and aimed to establish the underlying mechanisms. We induced traumatic brain injury in WKY rats using the weight‐drop technique, and 24 hours after severe TBI we found that myogenic responses of isolated middle cerebral arteries (MCAs) of TBI rats were blunted compared to control. The impaired myogenic responses of MCAs were restored after inhibiting mitochondrial oxidative stress (mitoTEMPO), eliminating H2O2 (PEG catalase) and blocking large‐conductance calcium‐activated potassium (BK Ca ) channels and transient receptor activated vanilloid channel 4 (TRPV4). We also found that H2O2‐induced dilation of MCAs involves the activation of BK Ca and TRPV4 channels, and that H2O2‐induced BK currents on vascular smooth muscle cells depend on the activation of TRPV4 channels. Our results suggest that after TBI excessive mitochondria‐derived H2O2 activates BK Ca channels via TRPV4 channel activation in the cerebrovascular wall, which diminishes pressure‐induced constriction of cerebral vessels. Future studies should elucidate the potential of inhibiting these vascular pathways to restore autoregulatory function after TBI in order to prevent TBI‐related secondary brain damage in patients suffered traumatic brain injury. Support or Funding Information This work was supported by grants from the Marie Curie Actions SMARTER 7 th Framework Program of the European Union 606998 (to NSz and AK), the Hungarian Academy of Sciences (the Bolyai Research Scholarship BO/00634/15 to PT), the Hungarian Brain Research Program (Grant No. KTIA_13_NAP‐A‐II/8 to PT, ECz and AB), National Center for Complementary and Alternative Medicine (R01‐AT006526 to ZU) and the Hungarian Scientific Research Fund (K108444 to AK).