ACTIVE H1-RECEPTORS PROTECT AGAINST THE HARMFUL EFFECTS OF H2-RECEPTORS IN A HISTAMINE INDUCED BRAIN EDEMA MODEL

Abstract

Active traumatic brain injury (TBI), high levels of histamine may participate in the pathophysiology of secondary brain injury. Histaminergic neurons project throughout the entire brain and are activate during brain diseases accompanied by edema. Interfering with histamine signaling influences the outcome after neurological insults in animals. We developed a histamine induced brain edema model in rats. Intracerebroventricular (ICV) application of histamine dose dependently impairs survival and water homeostasis in the adult rat brain as documented by increased intracranial pressure (ICP). In this new experimental model, selective histamine agonists and antigonists were tested. We show an acute toxic effect of H2-receptor activity, which disappears when H1-receptors are activated. We conclude that active H1-receptors protect against the toxic H2-effect. This shielding effect of H1-receptor activity is confirmed in several experiments. Therefore the use of central penetrating H1-antagonists must be avoided in patients with a suspected elevated histamine concentration in the brain, for example TBI-patients.