Intracerebral hemorrhage (ICH), a type of stroke, affects approximately 80,000 people per year in the United States and 2 million people worldwide. ICH occurs when a blood vessel within the brain ruptures, causing blood to come into direct contact with brain tissue. Proteins within the blood initiate a profound inflammatory response, worsening neurological injury due to swelling and leukocyte recruitment. One-third of leukocytes recruited to the mouse brain after experimental ICH are inflammatory monocytes. Inflammatory monocytes cause additional injury after heart attack and during atherosclerosis, but have never been studied in the context of ICH. This proposal contains preliminary data supporting the notion that inflammatory monocytes potentiate inflammation and worsen motor deficits following experimental ICH. The proposed experiments in specific aim 1 will use bone marrow chimeras, transgenic mice, neurobehavioral testing, and flow cytometry to identify the precise cell populations responsible for exacerbating neurological injury. Experiments outlined in specific aim 2 will show how these cells affect long-term recovery. Importantly, we will use a chemical inhibitor of inflammatory monocyte migration to evaluate these cells as a potential treatment target for humans with ICH. This project has high potential for translation to clinical trials because similar chemical inhibitors have already been FDA-approved for use in patients with diabetic nephropathy. This proposal outlines the scientific training of Matthew D. Hammond, a Ph.D. candidate in the Biomedical Science program at the University of Connecticut Health Center. Although the applicant is a part of the neuroscience concentration, much of the project is related to immunology. Because of this overlap, the training plan includes didactic coursework, mentorship, and regular seminar attendance in both neuroscience and immunology. The diverse didactic training described herein, complemented by sound research experiences, will prepare Matthew for a successful career in translational neuroimmunology research.

Public Health Relevance

Intracerebral hemorrhage is a type of stroke that affects 80,000 Americans each year, leaving about half severely disabled. This proposal will study how the immune system influences injury and recovery after intracerebral hemorrhage with a long-term goal of identifying treatment targets for this devastating disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1)
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Koenig, James I
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University of Connecticut
Schools of Medicine
United States
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Hammond, Matthew D; Taylor, Roslyn A; Mullen, Michael T et al. (2014) CCR2+ Ly6C(hi) inflammatory monocyte recruitment exacerbates acute disability following intracerebral hemorrhage. J Neurosci 34:3901-9
Taylor, Roslyn A; Hammond, Matthew D; Ai, Youxi et al. (2014) CX3CR1 signaling on monocytes is dispensable after intracerebral hemorrhage. PLoS One 9:e114472
Hammond, Matthew D; Ambler, William G; Ai, Youxi et al. (2014) ?4 integrin is a regulator of leukocyte recruitment after experimental intracerebral hemorrhage. Stroke 45:2485-7
Manwani, Bharti; Liu, Fudong; Scranton, Victoria et al. (2013) Differential effects of aging and sex on stroke induced inflammation across the lifespan. Exp Neurol 249:120-31