Abstract
BackgroundStroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB) disruption, and is often accompanied by increased release of arginine-vasopressin (AVP). AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2) and tolvaptan (V2) are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke.MethodsExperimental mice underwent the filament model of middle cerebral artery occlusion (MCAO) with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan) or orally (tolvaptan) for 48 hours. Physiological variables, neurological deficit scores (NDS), plasma and urine sodium and osmolality were recorded. Brain water content (BWC) and Evans Blue (EB) extravasation index were evaluated at the end point.ResultsBoth conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle) to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle). Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle) to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05).ConclusionContinuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke.
Highlights
Stroke is the fourth leading cause of death and the first leading cause of disability in the US [1]
Nine mice died during the 48-hour treatment period after middle cerebral artery occlusion (MCAO)/ reperfusion, but the mortality rate did not differ among groups (Table 1)
Body temperature during MCAO and reperfusion was within the physiological range, and body weights were measured before surgery and at the end point of the experiment (48 hours)
Summary
Stroke is the fourth leading cause of death and the first leading cause of disability in the US [1]. AVP activates V1a and V2 receptors [5] causing vasospasm [6], platelet aggregation [7], water retention, dilutional hyponatremia, and low plasma osmolality [8]. These events can quickly exacerbate stroke-evoked brain edema [9] and increase mortality rate [10] if plasma sodium level is not corrected. Blocking both V1a and V2 receptors after ischemic brain injury may prevent harmful pathophysiological events such as vasoconstriction, platelet aggregation, and hyponatremia. We conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
