A key component of this program project is bringing appropriate technical expertise to the Projects. This includes both new advances in human neuroimaging (an Imaging Core) and provision of key animal imaging techniques (an Animal Core). This scientific core will therefore have two parts. The Imaging Core will focus on key technical targets that are critical to improve the quality of data required for Project 3 (imaging of migraine effects in humans), and lay the groundwork for eventual human translation of work proposed for Project 1 (cortical spreading depression [CSD] treatment) or Project 2 (CSD and linkage to neuronal hyperstimulation) Specifically, the Imaging Core will provide two broad functions. First, the Core will provide technical support in four specific areas to directly assist in accomplishing the specific aims of Project 1 and Project 2 and ensure that the technical solutions are in place to accomplish the proposed aims. This will be accomplished both through the explicit goals of the Focus Areas as well as using the Imaging Core as a vehicle to assemble technical expertise to flexibly advise and assist the project leaders and their teams. Second, the Core will further develop additional technologies, in these same four specific focus areas, that will be helpful in elucidating the pathophysiology and treatment mechanisms of migraine: that is, to keep advancing the state of the art of neuroimaging in migraine. Part 2 of the Scientific Core will support Project 1 and 2 and perform imaging studies in rodents. Specifically, immunohistochemical studies will examine the phosphorylation state of the protein kinase Erk (Project 2) and examine the distribution of proteins encoded by mRNA with altered expression following chronic antimigraine drug treatment (Project 1). In addition, in situ hybridization studies will confirm the results of gene array studies (Project 1), while in vitro receptor autoradiography will examine the density and affinity of various glutamate receptor subtypes that may be involved in the generation/propagation ofCSD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS035611-13
Application #
7905043
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
13
Fiscal Year
2009
Total Cost
$242,740
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Burstein, Rami; Blake, Pamela; Schain, Aaron et al. (2017) Extracranial origin of headache. Curr Opin Neurol 30:263-271
Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer et al. (2015) Migraine prophylaxis, ischemic depolarizations, and stroke outcomes in mice. Stroke 46:229-36
Ayata, Cenk; Lauritzen, Martin (2015) Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature. Physiol Rev 95:953-93
Hadjikhani, Nouchine; Ward, Noreen; Boshyan, Jasmine et al. (2013) The missing link: enhanced functional connectivity between amygdala and visceroceptive cortex in migraine. Cephalalgia 33:1264-8
Burstein, Rami; Strassman, Andrew; Moskowitz, Michael (2012) Can cortical spreading depression activate central trigeminovascular neurons without peripheral input? Pitfalls of a new concept. Cephalalgia 32:509-11
Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yuzawa, Izumi et al. (2012) Migraine mutations increase stroke vulnerability by facilitating ischemic depolarizations. Circulation 125:335-45
Borsook, D; Burstein, R (2012) The enigma of the dorsolateral pons as a migraine generator. Cephalalgia 32:803-12
Arboleda-Velasquez, Joseph F; Manent, Jan; Lee, Jeong Hyun et al. (2011) Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease. Proc Natl Acad Sci U S A 108:E128-35
Zhang, Xichun; Levy, Dan; Kainz, Vanessa et al. (2011) Activation of central trigeminovascular neurons by cortical spreading depression. Ann Neurol 69:855-65
Eikermann-Haerter, Katharina; Yuzawa, Izumi; Dilekoz, Ergin et al. (2011) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome mutations increase susceptibility to spreading depression. Ann Neurol 69:413-8

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