The overall goal of this proposal is to define mechanisms of neuronal injury following focal and global cerebral ischemia in adult and pediatric animals, and to define developmental cerebrovascular regulation in fetal and newborn animals. The Program represents a multidisciplinary, mechanistic approach involving interactive, productive investigators with complimentary areas of expertise who have long been committed to studies of the cerebral circulation and ischemia. One major aim will be to integrate the activities of various disciplines such that the interrelationships will result in a greater scientific contribution than could be achieved if each project were pursued individually. The Program has two themes: first, molecular, neuropathologic, physiologic and neurobehavioral approaches are proposed to examine the mechanisms of neuronal injury and neuroprotection from stroke and cardiac arrest/CPR (focal and global cerebral ischemia). We will determine the neuroprotective mechanisms associated with sigma receptor signaling, estrogen, and superoxide dismutase/nitric oxide. Also, developmental cerebrovascular regulation focusing on mechanisms of vasodilation will be characterized in the fetus and newborn. Second, state-of-the-art molecular, neuropathology, physiology and neurobehavioral approaches are used throughout the Program. The Program has several important strengths: first, the investigators have a long history of interactive studies of the brain and its vasculature under normal and pathophysiological conditions. Our preliminary data indicate feasibility of our new approaches and demonstrate evidence of integration of the new additions to the Program. Third, the investigators are leaders in the field concerning mechanisms of neuronal injury, cerebrovascular regulation, and ischemia. Fourth, the investigators use sophisticated physiological approaches and molecular, neuropathological and neurobehavioral approaches have been incorporated to facilitate novel insight into neuronal injury and cerebrovascular regulatory mechanisms. The Program consists of four projects: 1) Sigma Receptor Signaling in Focal Cerebral Ischemia; 2) Gender Differences in Stroke; 3) Cardiac Arrest and Resuscitation: Mechanisms of Brain Injury; and 4) Developmental Cerebrovascular Regulation in the Fetus and Newborn, and is supported by four Core facilities: 1) Administration; 2) Neuropathology; 3) Neurochemistry; and 4) Neurobehavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS020020-18
Application #
6330414
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Jacobs, Tom P
Project Start
1983-12-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
18
Fiscal Year
2001
Total Cost
$1,112,567
Indirect Cost
Name
Johns Hopkins University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Fonken, Laura K; Gaudet, Andrew D; Gaier, Kristopher R et al. (2016) MicroRNA-155 deletion reduces anxiety- and depressive-like behaviors in mice. Psychoneuroendocrinology 63:362-9
Ni, Xinli; Yang, Zeng-Jin; Wang, Bing et al. (2012) Early antioxidant treatment and delayed hypothermia after hypoxia-ischemia have no additive neuroprotection in newborn pigs. Anesth Analg 115:627-37
Ni, Xinli; Yang, Zeng-Jin; Carter, Erin L et al. (2011) Striatal neuroprotection from neonatal hypoxia-ischemia in piglets by antioxidant treatment with EUK-134 or edaravone. Dev Neurosci 33:299-311
Woodworth, K Nina; Palmateer, Julie; Swide, Joseph et al. (2011) Short- and long-term behavioral effects of exposure to 21%, 40% and 100% oxygen after perinatal hypoxia-ischemia in the rat. Int J Dev Neurosci 29:629-38
Yang, Sufang; Abrahams, Matthew S; Hurn, Patricia D et al. (2011) Local anesthetic Schwann cell toxicity is time and concentration dependent. Reg Anesth Pain Med 36:444-51
Nakano, Takaaki; Hurn, Patricia D; Herson, Paco S et al. (2010) Testosterone exacerbates neuronal damage following cardiac arrest and cardiopulmonary resuscitation in mouse. Brain Res 1357:124-30
Yang, Zeng-Jin; Carter, Erin L; Torbey, Michel T et al. (2010) Sigma receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine modulates neuronal nitric oxide synthase/postsynaptic density-95 coupling mechanisms and protects against neonatal ischemic degeneration of striatal neurons. Exp Neurol 221:166-74
Ohata, Hiroto; Gebremedhin, Debebe; Narayanan, Jayashree et al. (2010) Onset of pulmonary ventilation in fetal sheep produces pial arteriolar constriction dependent on cytochrome p450 omega-hydroxylase activity. J Appl Physiol 109:412-7
Zhu, W; Wang, L; Zhang, L et al. (2010) Isoflurane preconditioning neuroprotection in experimental focal stroke is androgen-dependent in male mice. Neuroscience 169:758-69
Neigh, Gretchen N; Karelina, Kate; Glasper, Erica R et al. (2009) Anxiety after cardiac arrest/cardiopulmonary resuscitation: exacerbated by stress and prevented by minocycline. Stroke 40:3601-7

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