Introduction
Brain edema formation is one of the most important mechanisms responsible for brain damage following ischemic stroke. Despite considerable efforts, no specific therapy is available yet. Arginine vasopressin (AVP) regulates cerebral water homeostasis and has been involved in brain edema formation. In the current study we investigated the role of AVP V1 and V2 receptors on brain damage, brain edema formation, and functional outcome after transient focal cerebral ischemia, a condition comparable to that of stroke patients undergoing thrombolysis.
Materials & Methods
C57/BL6 mice were subjected to 60 min MCAo followed by 23 h of reperfusion. Five minutes after MCAo 100 or 500 ng of [deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-vasopressin (AVP V1 receptor antagonist) or [adamantaneacetyl(1), O-Et-D-Tyr(2), Val(4), Abu(6), Arg(8,9)]-vasopressin (AVP V2 receptor antagonist) were injected into the left ventricle.
Results
Inhibition of AVP V1 receptors reduced infarct volume in a dose dependent manner by 54 and 70% (to 29 ± 13 and 19 ± 10 mm3 vs. 63+/−17 mm3 in controls; p<0.001), brain edema formation by 67% (to 80.4 ± 1.0 vs. 82.7 ± 1.2% in controls; p<0.001), blood brain barrier disruption by 75% (p<0.001), and functional deficits 24 h after ischemia, while V2 receptor inhibition had no effect.
Summary & Conclusion
The current findings indicate that AVP V1 but not V2 receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. Although, further studies are needed to clarify the mechanisms of neuroprotection, AVP V1 receptors seem to be promising targets for the treatment of ischemic stroke.