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Mast cells can secrete histamine in response to extrinsic stimuli. Histamine plays a role in the development of brain edema and can induce histamine receptor H3 (HRH3) expression in the brain to provide protective feedback effects against histamine neurotoxicity. We investigated time-dependent changes in dural mast cell numbers and HRH3 expression in the brain for one to 14 days after traumatic brain injury in a controlled cortical impact model in the rat. The number of tryptase-immunoreactive dural mast cells at the site of impact was significantly decreased one and four days after the injury. Furthermore, immunoreactivity and messenger RNA (mRNA) expression of HRH3 at the underlying cortical contusion site were significantly increased one and four days after the injury. These data suggest that histamine released from degranulated unstainable mast cells induces a transient increase in presynaptic autoinhibitory HRH3 immunoreactivity and mRNA expression as a mechanism to counteract histamine neurotoxicity., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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]