Role of Arginine Vasopressin V₁ and V₂ Receptors for Brain Damage After Transient Focal Cerebral Ischemia

Abstract

Brain edema formation is one of the most important mechanisms responsible for brain damage after 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 V 1 and V 2 receptors on brain damage, brain edema formation, and functional outcome after transient focal cerebral ischemia, a condition comparable with that of stroke patients undergoing thrombolysis. C57/BL6 mice were subjected to 60-min middle cerebral artery occlusion (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) .2% in controls; Po0.001), blood-brain barrier disruption by 75% (Po0.001), and functional deficits 24 h after ischemia, while V 2 receptor inhibition had no effect. The current findings indicate that AVP V 1 but not V 2 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 V 1 receptors seem to be promising targets for the treatment of ischemic stroke.

Multiple Sites of Vasopressin Synthesis in the Injured Brain

“…These clinical observations are consistent with the results obtained from animal studies, in which AVP was shown to promote disruption of the BBB, exacerbate cerebral edema, and augment the loss of neural tissue in various forms of brain injury (e.g., Vakili et al, 2005;Szmydynger-Chodobska et al, 2010). Brain injury has also been shown to result in a substantial increase in the expression of the V 1a receptor (AVPR1A) on cortical astrocytes and on the cerebrovascular endothelium (Szmydynger-Chodobska et al, 2004), suggesting that these two types of parenchymal cells are the primary targets for AVP in the injured brain.…”

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

“…21,[24][25][26] Previous work demonstrating that vasopressin may induce brain edema 20,21,56 is supported by multiple studies showing that edema is abolished by blocking the V1aR receptors. [24][25][26][27][28][29] The present results demonstrate that V1aR inhibition accelerates the recovery of [Na + ] e supporting its potential to blunt the ionic dysfunction that leads to edematous changes. Taken together, out findings suggest that SR49059 and other V1aR inhibitors may have potential as therapeutic agents for treating cellular edema by both speeding post-injury ionic recovery and reducing injury-induced elevation of ICP following CCI.…”

“…Further, experimental models of intracerebral hemorrhage, middle cerebral artery occlusion, ischemia, and cold and traumatic brain injury have demonstrated that V1aR inhibition reduces brain edema. [22][23][24][25][26][27][28][29][30][31] The underlying mechanism of this response has been attributed to either modulation of vasopressin in the brain parenchyma 17 or its interaction with aquaporin-4 (AQP4). AQP4 is the predominant water channel in the brain and has a significant role in the pathophysiology of brain edema.…”

Copeptin adds prognostic information after ischemic stroke

“…38 Data from experimental studies imply that AVP plays a role in brain edema formation as blocking of AVP receptors attenuates brain edema in ischemic mice models. 39 Some limitations merit attention. To assess complications, a time-to-event analysis would have been ideal.…”