Abstract
Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.
Highlights
After the onset of stroke and head trauma, brain edema often occurs
Vasogenic edema, which is accompanied by elevation of intracranial pressure, is induced by extravasation of blood proteins through the disrupted blood-brain barrier (BBB) [2]
To clarify possible roles of ET-1 in vasogenic edema formation, expression of ET-1 was determined in our mouse cold injury model
Summary
Brain edema is a potentially fatal pathological state where accumulation of brain water impairs nerve function owing to elevation of intracranial pressure. Vasogenic edema is accompanied by disruption of the blood-brain barrier (BBB) and is mainly involved in the elevation of intracranial pressure. Disruption of the BBB allows extravasation of blood proteins into brain parenchyma and water accumulation in damaged areas, which underlies the pathogenesis of vasogenic edema [2,3]. Astrocytes are in close contact with vascular endothelial cells via the end-feet of their processes. Because this anatomical structure creates restricted permeability to blood components, a large part of the BBB function is due to the interactions between astrocytes and vascular endothelial cells
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have