Project V seeks to establish the mechanisms by which electrical stimulation of the cerebellar fastigial nucleus (FN) reduces the volume of the focal ischemic infarction produced by permanent occlusion of the middle cerebral artery (MCAO) in rat. Specifically, it tests the hypotheses that the central neurogenic protection results from interaction of two events: (a) a reduction in neuronal excitability, and (b) suppression of inflammatory reactions. Study I will determine whether (a) electrical stimulation of FN in anesthetized rats reduces the depolarizing (DC) waves generated in the ischemic penumbra after MCAO (b) FN stimulation in normal rats alters the threshold and pattern of spreading cortical depression; and (c) in case that excitability is altered, if the response can be attributed to alteration in neuronal Kplus channel function. Study II will examine whether (a) MCAO will induce, in brain, expression of the mRNAs and/or protein products for the pro-inflammatory molecules iNOS and lL1-beta; and the endothelial adhesion molecules ICAM and VCAM;(b) FN stimulation reduces the expression of these molecules by MCAO; (c) the inflammatory reactivity of vessels isolated from FN-stimulated brains is reduced compared to non-stimulated brains; (d) FN stimulation reduces the responses to lL-1 injection in brain; (e) FN stimulation modifies the transcription factor NFKbeta, which coordinates expression of inflammatory genes; (f) FN stimulation induces the mRNA and/or proteins for the anti-inflammatory cytokines lL4, lL10, lL-1Ra and/or TGFbeta.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Weill Medical College of Cornell University
New York
United States
Zip Code
Glass, Michael J; Chan, June; Pickel, Virginia M (2017) Ultrastructural characterization of tumor necrosis factor alpha receptor type 1 distribution in the hypothalamic paraventricular nucleus of the mouse. Neuroscience 352:262-272
Takahashi, Reisuke H; Capetillo-Zarate, Estibaliz; Lin, Michael T et al. (2013) Accumulation of intraneuronal ýý-amyloid 42 peptides is associated with early changes in microtubule-associated protein 2 in neurites and synapses. PLoS One 8:e51965
Misono, K; Lessard, A (2012) Apomorphine-evoked redistribution of neurokinin-3 receptors in dopaminergic dendrites and neuronal nuclei of the rat ventral tegmental area. Neuroscience 203:27-38
Van Kempen, Tracey A; Milner, Teresa A; Waters, Elizabeth M (2011) Accelerated ovarian failure: a novel, chemically induced animal model of menopause. Brain Res 1379:176-87
Williams, Tanya J; Akama, Keith T; Knudsen, Margarete G et al. (2011) Ovarian hormones influence corticotropin releasing factor receptor colocalization with delta opioid receptors in CA1 pyramidal cell dendrites. Exp Neurol 230:186-96
Williams, T J; Milner, T A (2011) Delta opioid receptors colocalize with corticotropin releasing factor in hippocampal interneurons. Neuroscience 179:9-22
Williams, Tanya J; Torres-Reveron, Annelyn; Chapleau, Jeanette D et al. (2011) Hormonal regulation of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus. Neurobiol Learn Mem 95:206-20
Spencer-Segal, Joanna L; Waters, Elizabeth M; Bath, Kevin G et al. (2011) Distribution of phosphorylated TrkB receptor in the mouse hippocampal formation depends on sex and estrous cycle stage. J Neurosci 31:6780-90
Williams, Tanya J; Mitterling, Katherine L; Thompson, Louisa I et al. (2011) Age- and hormone-regulation of opioid peptides and synaptic proteins in the rat dorsal hippocampal formation. Brain Res 1379:71-85
Arévalo, Juan Carlos; Wu, Synphen H; Takahashi, Takuya et al. (2010) The ARMS/Kidins220 scaffold protein modulates synaptic transmission. Mol Cell Neurosci 45:92-100

Showing the most recent 10 out of 294 publications