Intracerebral hemorrhage (ICH) is a devastating type of stroke affecting more than 70,000 patients in the U.S. each year, yet there is no specific treatment available. Stimulation of the innate immune system at the site of hemorrhage leads to inflammation and progressive brain injury. In a murine model of ICH, we have demonstrated that ICH leads to the recruitment of blood-derived monocytes and inflammatory monocytes to the perihematomal region and the activation and proliferation of microglia. These events are concomitant with progressive functional disability. The proposed studies will utilize transgenic mice, bone marrow chimeras, and in vitro assays to determine the individual effects of each population on the immune response and functional outcomes after ICH.
Specific Aim 1 will determine the roles of the CX3CR1+ and CCR2+Gr1+ monocyte populations in injury after ICH.
In Specific Aim 2, the role of chemokine receptors CX3CR1 and CCR2 on microglial activation will be investigated. Together these studies will determine the translational potential of targetin these cellular responses in the treatment of ICH. This proposal outlines the training of Lauren Sansing, MD, an Assistant Professor in Neurology at the University of Connecticut Health Center, from mentored to independent translational researcher. Career development plans include formal coursework in immunology, regular seminar attendance in both immunology and neuroscience, and conference participation. These didactic components will complement the training involved in executing the research project and optimally position Dr. Sansing for a career as an independent investigator in translational stroke research.

Public Health Relevance

Intracerebral hemorrhage is a type of stroke that affects 70,000 people in the U.S. each year and causes half of the patients to die or be left severely disabled. This proposal will study the immune pathways responsible for brain injury surrounding the hemorrhage and hopes to identify new targets for treatment.

Agency
National Institute of Health (NIH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS078110-03
Application #
8716823
Study Section
Neurological Sciences Training Initial Review Group (NST)
Program Officer
Koenig, James I
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
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
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
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