Neurological complications after mild head injury can include vasogenic edema and/or subsequent development of epilepsy, conditions associated with elevated histamine. In the present study we assessed the potential of mast cells located in the dura mater to contribute to elevated cortical histamine and breakdown of the blood-brain barrier after minor head injury, modeled by either a parietal craniectomy or producing a groove in (scoring) the parietal bone surface to model a grazing head injury. We measured the following effects at 5-20 min after a unilateral parietal craniectomy (rats) or unilateral scoring of the parietal bone (mice): (1) mast cell integrity in subjacent dura mater; (2) subjacent vs. contralateral histamine in dura mater and cerebral cortex; (3) vascular permeability of cerebral cortical blood vessels subjacent to the injury, and; (4) the effects of an H(2)-receptor antagonist on cerebral cortical vascular permeability. RESULTS Dural mast cells subjacent to the craniectomy became activated (degranulated) concomitant with (1) decreased histamine in dura mater subjacent to the craniectomy; (2) increased histamine in the subjacent cerebral cortex; and (3) extravasation of Evans blue-albumin which stained the subjacent cerebral cortex, indicating a localized breakdown of the blood-brain barrier. Similar results were observed in mice after scoring the parietal bone surface and, additionally, pretreatment with the histamine H(2)-receptor antagonist zolantadine (1 h before injury) dose-dependently inhibited extravasation of Evans blue-albumin. We conclude that even a minor grazing injury of the skull, in the absence of penetrating brain injury or concussion, can activate dural mast cells and elevate cortical histamine, a novel mechanism with potential contributions to neurotraumatic complications arising from a relatively minor or grazing head wound.