Abstract
The aim of this study was to compare the effects of conivaptan, an arginine vasopressin antagonist, and mannitol, a sugar alcohol, on cerebral ischemia-induced brain injury and edema in rats. Fifty-eight 8-week-old male Sprague Dawley rats were randomly divided into five groups: control, ischemia-reperfusion (I/R)+saline, I/R+mannitol, I/R+10 mg/ml conivaptan, and I/R+20 mg/ml conivaptan. Cerebral ischemia was induced by common carotid artery occlusion for 30 minutes. Saline, mannitol, or conivaptan were administered intravenously at the onset of reperfusion. Blood and brain tissue samples were taken at the 6th hour of reperfusion. The electrolytes (Na+-K+-Cl-), osmolality, arginine vasopressin, albumin, progranulin (PGRN), neuron-specific enolase (NSE), and myeloperoxidase activity were measured in rat serum samples. Brain frontal/hippocampal sections were stained with hematoxylin-eosin and TUNEL techniques to evaluate histopathological changes. Statistical analyses revealed that conivaptan caused significant changes in the electrolyte, NSE, and PGRN levels and osmolality when compared with mannitol. Conivaptan treatment showed positive effects on serum biochemistry and tissue histology. Our findings revealed that conivaptan shows more diuretic activity than mannitol and triggers neither any damages nor edema in the brain tissue. This study may provide beneficial information for the development of treatment strategies for ischemia-related cerebrovascular diseases.
Highlights
The formation of brain edema (BE), a continuous process with an intense intracellular and extracellular ion and water exchange [1], is one of the most important acute/subacute complications of cerebral injuries
Serum Cl− levels decreased in the I/R group compared to the control significantly (p
In which electrolyte levels were examined to assess the fluid–electrolyte balance, it was observed that the serum Na+ and Cl− levels in the I/R group decreased significantly compared to the control
Summary
The formation of brain edema (BE), a continuous process with an intense intracellular and extracellular ion and water exchange [1], is one of the most important acute/subacute complications of cerebral injuries. The osmotherapy applied as a part of the medical treatment algorithms is of great importance in the management of cerebral edema and increased intracranial pressure (ICP) following brain injury [3]. A widely used osmotic diuretic agent for the treatment of BE and high ICP for many years [4], cannot meet the anticipated efficacy because it can cause serious side effects and more fluid to be drawn into the tissues [5]. It has been suggested that the AVP hypersecretion plays a critical role in the BE formation, leading to vasospasm, water retention, dilutional hyponatremia, and low plasma osmolality [7]. AVP receptors might be preferred as a crucial therapeutic target [8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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 call