The effect of histamine, a traumatic brain injury mediator, on the function of aquaporin-4 in rat brain in vivo

Abstract

The high levels of histamine in brain after traumatic brain injury and the observed influence of histamine on aquaporin-1 (AQP-1) localization in gastric cells, lead to the hypothesis that histamine could play a major role in the pathophysiology of brain edema An intracerebroventricular (ICV) histamine induced brain edema model was developed in rats. Infusion of concentrations >= 50 mM histamine resulted in a dose-dependent intracranial pressure (ICP) increase and death. Furthermore, histological experiments showed the internalization of membrane-expressed AQP4 after histamine challenge. The decreased fraction of functional membrane-associated AQP4 might result in an increased intracranial p[ressure. In this new experimental rat mode, the functional activity of novel treatment options for increased ICP, IV or ICV administration, can readily be tested.