Active H(1)-receptors protect against the harmful effects of H(2)-receptors in a histamine induced brain edema model

Abstract

Inspired by the high histamine levels in the brains of traumatic brain injury (TBI) patients and earlier in vitro results with histamine in a cell swelling model, a histamine induced brain ederna model was developed in rats. In this new experimental model, selective histamine agonists and antagonists were tested. An acute lethal effect is caused by H(1)-antagunism after intracerebroventricular (ICV) histamine infusion. Moreover H(2)-receptor activation results in toxic effects, which are reduced with H1-receptor stimulation. These data indicate that active H(1)-receptors protect against the toxic II,-effect. This shielding effect of H(1)-receptor activity is confirmed in several experiments. Therefore central penetrating H(1)-antagonists must be used with care in patients with a suspected elevated histamine concentration in the brain, for example TBI-patients.