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Intracerebroventricular application of S100B selectively impairs pial arteriolar dilating function in rats
- Source :
- Brain research. 1634
- Publication Year :
- 2015
-
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 (p0.05) and the endothelial-dependent vasodilator ACh (p0.05), 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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Subarachnoid hemorrhage
Adenosine
Vasodilator Agents
Receptor for Advanced Glycation End Products
Vasodilation
S100 Calcium Binding Protein beta Subunit
S-Nitroso-N-Acetylpenicillamine
Hypercapnia
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Animals
Receptor
Molecular Biology
business.industry
General Neuroscience
Snap
medicine.disease
Sciatic Nerve
Acetylcholine
Electric Stimulation
Rats
Arterioles
030104 developmental biology
Endocrinology
Infusions, Intraventricular
Anesthesia
cardiovascular system
Pia Mater
Neurology (clinical)
medicine.symptom
business
030217 neurology & neurosurgery
Intravital microscopy
Developmental Biology
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 18726240
- Volume :
- 1634
- Database :
- OpenAIRE
- Journal :
- Brain research
- Accession number :
- edsair.doi.dedup.....f16994d87cfd7765e95c913efccece02