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2. Mechanism of exacerbation of traumatic brain injury under warfarin anticoagulation in male mice.

Author

Tatara, Yuki, Nakao, Ken-ichiro, Shimada, Ryo, and Kibayashi, Kazuhiko

Subjects
*INTRACRANIAL hemorrhage, *BRAIN injuries, *CEREBRAL hemorrhage, *WARFARIN, *CYTOCHROME P-450
Abstract

Introduction: Traumatic brain injury (TBI) is exacerbated in patients on antithrombotic medications, with warfarin leading to increased bleeding in some cases. However, the extent to which this bleeding increases lethality and its long-term effects remain unclear. This study aimed to investigate the exacerbation of TBI by warfarin treatment and comprehensively evaluate the impact of TBI on the anticoagulant effects of warfarin. Methods: We induced TBI in mice after pre-treatment with warfarin and analyzed TBI exacerbation based on the prothrombin time-international normalized ratio (PT-INR) value, brain hemorrhage volume, blood warfarin and 7-hydroxywarfarin levels, and cytochrome P450 2C9 (CYP2C9) protein expression. C57BL/6J mice fed with a vitamin K-deficient diet received oral warfarin (low dose, 0.35 mg/kg/24 h; high dose, 0.70 mg/kg/24 h), and focal brain damage was induced in the cerebral cortices using a brain contusion device. Warfarin-treated injured mice were compared with sham-treated mice (scalp incision alone or scalp incision + bone window formation). Results: When warfarin was administered, the PT-INR value and brain hemorrhage volume associated with cerebral contusion increased on the first day post-injury. High blood warfarin and 7-hydroxywarfarin levels were observed. However, no significant differences in CYP2C9 expression were observed between the groups. Discussion: Elevated warfarin levels post-injury can increase cerebral hemorrhage risk, possibly worsening TBI. TBI might also elevate warfarin levels, heightening its anticoagulant effects. Therefore, assessing injury severity levels and PT-INR values in patients with TBI on warfarin is crucial to anticipate delayed bleeding risks. [ABSTRACT FROM AUTHOR]

Published
2024
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25. General pharmacological action of 4-(o-Benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016, bifemelane hydrochloride). Influence on respiratory and cardiovascular systems, renal function, autonomic nervous system, isolated smooth muscle and digestive organs.

Author

NARIMATSU, Akihiro, primary, NAKAO, Ken-ichiro, additional, IKOMA, Hidenobu, additional, EGAWA, Mitsuo, additional, KITADA, Yoshimi, additional, YAMAZAKI, Satoshi, additional, UMEZU, Kohei, additional, MIYAKE, Motoyoshi, additional, NISHIMURA, Etsuko, additional, HASHIMOTO, Noriko, additional, SUZUKI, Reiko, additional, YOSHIDA, Etsuko, additional, and TOBE, Akihiro, additional

Published
1986
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26. General pharmacological action of tritoqualine (TRQ; (.+-.)-(R*)-7-amino-4,5,6-triethoxy-3-((R*)-5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo (4,5-g) isoquinolin-5-yl) phthalide).

Author

NARIMATSU, Akihiro, primary, NAKAO, Ken-ichiro, additional, EGAWA, Mitsuo, additional, HARA, Hiroto, additional, KITADA, Yoshimi, additional, YAMAZAKI, Satoshi, additional, MIYAKE, Motoyoshi, additional, TANAKA, Tadashi, additional, KATAYAMA, Sohta, additional, HASHIMOTO, Noriko, additional, DOI, Akiko, additional, YOSHIDA, Etsuko, additional, SUZUKI, Reiko, additional, KAWAHARA, Kozue, additional, and TOBE, Akihiro, additional

Published
1986
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