title: Intracerebroventricular application of S100B selectively impairs pial arteriolar dilating function in rats.
abstract: S100B is an astrocyte-derived protein that can act through the receptor for advanced glycation endproducts (RAGE) to mediate either "trophic" or "toxic" responses. Its levels increase in many neurological conditions with associated microvascular dysregulation, such as subarachnoid hemorrhage (SAH) and traumatic brain injury. The role of S100B in the pathogenesis of microvasculopathy has not been addressed. This study was designed to examine whether S100B alters pial arteriolar vasodilating function. Rats were randomized to receive (1) artificial cerebrospinal fluid (aCSF), (2) exogenous S100B, and (3) exogenous S100B+the decoy soluble RAGE (sRAGE). S100B was infused intracerebroventricularly (icv) using an osmotic pump and its levels in the CSF were adjusted to achieve a concentration similar to what we observed in SAH. After 48 h of continuous icv infusion, a cranial window/intravital microscopy was applied to animals for evaluation of pial arteriolar dilating responses to sciatic nerve stimulation (SNS), hypercapnia, and topical suffusion of vasodilators including acetylcholine (ACh), s-nitroso-N-acetyl penicillamine (SNAP), or adenosine (ADO). Pial arteriolar dilating responses were calculated as the percentage change of arteriolar diameter in relation to baseline. The continuous S100B infusion for 48 h was associated with reduced responses to the neuronal-dependent vasodilator SNS (p<0.05) and the endothelial-dependent vasodilator ACh (p<0.05), compared to controls. The inhibitory effects of S100B were prevented by sRAGE. On the other hand, S100B did not alter the responses elicited by vascular smooth muscle cell-dependent vasodilators, namely hypercapnia, SNAP, or ADO. These findings indicate that S100B regulates neuronal and endothelial dependent cerebral arteriolar dilation and suggest that this phenomenon is mediated through RAGE-associated pathways.
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Benjarat
authors.initials: B
authors.lastname: Changyaleket
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, United States; Department of Pathology, University of Illinois at Chicago, Chicago, IL, United States. Electronic address: hlxu@uic.edu.
authors.forename: Haoliang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vetri
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Chanannait
authors.initials: C
authors.lastname: Paisansathan
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Zhao Zhong
authors.initials: ZZ
authors.lastname: Chong
authors.affiliation: Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Dale A
authors.initials: DA
authors.lastname: Pelligrino
authors.affiliation: Department of Neurology and Rehabilitation, University of Illinois at Chicago, Chicago, IL, United States.
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Testai
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000241:Adenosine / Q000008:administration & dosage; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D006935:Hypercapnia / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D010841:Pia Mater / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000008:administration & dosage; D064568:S100 Calcium Binding Protein beta Subunit / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000502:physiology*; D012584:Sciatic Nerve / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: C000593874:Ager protein, rat; D000067759:Receptor for Advanced Glycation End Products; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D014665:Vasodilator Agents; D026423:S-Nitroso-N-Acetylpenicillamine; D000241:Adenosine; D000109:Acetylcholine
keywords: Pial arteriole; S100B; Subarachnoid hemorrhage; The receptor of advanced glycation endproducts; Vasodilation