This application lists 5 specific aims intended to further define the anatomy, biochemistry, pharmacology, physiology and function of the sensory innervation of cephalic blood vessels. We have previously postulated that such a system is importantly involved in the pathophysiology of vascular headaches and have recent data to suggest that this system becomes modified by the presence of blood in the subarachnoid space. A multidisciplinary approach will explore the aims using a) axonal transport studies, immunohistochemistry and in situ hybridization studies to further determine the neural connectivity between perivascular sensory fibers surrounding dural and pial arteries, cell bodies in dorsal root and trigeminal ganglia, and central endings in brain stem; b) vascular permeability studies in dura will use iodinated albumin or horseradish peroxidase to define the relationship between perivascular afferents and the observed enhanced permeability in dura following chemical injections, electrical trigeminal stimulation or sensitization responses. The already-noted potent inhibitory effects of ergot alkaloids and neurotransmitter agonists and receptor blockers on the natural history of this leakage will be further defined mechanistically, c) the effects of adding blood into the subarachnoid space on sensory transmitter levels and peptide synthesis within blood vessels and sensory ganglia will be characterized by RIA and the mechanisms clarified (insitu and Northern blot analysis) to extend our preliminary data showing significant disruption in neurotransmitter turnover shortly after the induction of hemorrhage. By taking such an approach, we hope to explore the possible roles for the trigeminovascular system in cerebrovascular regulation during health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021558-06
Application #
3402773
Study Section
Neurology A Study Section (NEUA)
Project Start
1985-02-01
Project End
1992-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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Limmroth, V; Lee, W S; Moskowitz, M A (1996) GABAA-receptor-mediated effects of progesterone, its ring-A-reduced metabolites and synthetic neuroactive steroids on neurogenic oedema in the rat meninges. Br J Pharmacol 117:99-104
Limmroth, V; Cutrer, F M; Moskowitz, M A (1996) Neurotransmitters and neuropeptides in headache. Curr Opin Neurol 9:206-10
Cutrer, F M; Moskowitz, M A (1996) Wolff Award 1996. The actions of valproate and neurosteroids in a model of trigeminal pain. Headache 36:579-85
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Cutrer, F M; Limmroth, V; Ayata, G et al. (1995) Attenuation by valproate of c-fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin. Br J Pharmacol 116:3199-204
Cutrer, F M; Schoenfeld, D; Limmroth, V et al. (1995) Suppression by the sumatriptan analogue, CP-122,288 of c-fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin. Br J Pharmacol 114:987-92

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