Abstract 10081: Inhibition of RAGE-Related Pathway Prevents Subarachnoid Hemorrhage (sah)-Associated Neuroinflammation and Neurologic Dysfunction in Rats
Recent study from our laboratory indicated that, in SAH, activation of the receptor for advanced glycation end-products (RAGE)-related pathway contributes to cerebral arteriolar dilating dysfunction. Since RAGE activation is linked to the occurrence and exacerbation of inflammatory reactions, and neuroinflammation is a contributor to cerebrovascular dysfunction, we tested the following hypotheses: (1) RAGE is involved in post-SAH neuroinflammation; and (2) preventing RAGE activation, using the RAGE decoy protein, soluble RAGE (sRAGE), attenuates SAH-associated neuroinflammation, and recovers neurological function. Rats were randomized into three groups: sham surgical controls, vehicle-treated SAH controls, and sRAGE-treated SAH rats. The SAH model involved suture perforation of the anterior cerebral artery. Neuroinflammation was assessed by pial venular leukocyte adhesion (PVLA) on day 2 post-SAH. PVLA, viewed through a closed cranial window, was expressed as the % pial venular area occupied by adherent rhodamine-6G-labeled leukocytes. Neurobehavioral function, which included spontaneous activity, muscle tone, and neurologic reflex was evaluated during the post-SAH recovery period (up to 3 days). Compared to the sham surgical group, a marked increased PVLA was observed in vehicle-treated animals (10.78±2.20 % vs 2.72±0.09 % in sham), with a profound leukocyte extravascular infiltration revealed during extended observation period (infiltration index was 4.83±2.82% of the venular area). No sign of infiltration was found in the sham surgical group. sRAGE treatment significantly decreased SAH-associated PVLA to 5.53± 0.29%, with complete suppression of leukocyte extravascular migration. Additionally, a significant improvement in SAH-related neurological deficits was found in the presence of sRAGE. In summary, RAGE plays an important role in mediating post-SAH neuroinflammation, which may contribute to SAH-associated neurological dysfunction.
- © 2011 by American Heart Association, Inc.