Brain edema formation was investigated in the vasopressin-deficient Brattleboro rat using a middle cerebral artery occlusion model of early ischemic injury. Water and sodium accumulation after 4 h of ischemia were attenuated 36 and 20%, respectively, in the Brattleboro strain as compared to the control Long–Evans strain. This effect was independent of differences in animal size and state of hydration. In addition, measurements of cerebral blood flow indicated that Brattleboro and Long–Evans rats had equal levels of ischemia following middle cerebral artery occlusion. Systemic treatment of Brattleboro rats with vasopressin normalized their serum electrolyte concentrations and osmolarity but did not alter sodium or water accumulation in the ischemic brain. In contrast, intraventricular administration of vasopressin in Brattleboro rats increased edema formation to that seen in control rats. The reduced water and sodium accumulation in Brattleboro rats subjected to middle cerebral artery occlusion may be related to alterations in blood–brain barrier permeability since the blood-to-brain sodium flux was 36% less in the ischemic tissue of the Brattleboro as compared to the Long–Evans strain. These results support the hypothesis that central vasopressin is a regulator of brain volume and electrolyte homeostasis. Furthermore, our findings suggest a role for central vasopressin in the development of ischemic brain edema.
Targeting platelet glycoprotein VI attenuates progressive ischemic brain damage before recanalization during middle cerebral artery occlusion in mice
