ANIMAL MODELS: CARDIOVASCULAR DISEASE, CNS INJURY AND ULTRAFINE PARTICLE BIOKINETICS
Impact/Purpose:
The animal studies are designed to test our central hypothesis that ambient ultrafine (UF) particles induce oxidative injury in target cells of the cardiovascular system, resulting in adverse health effects in susceptible parts of the population. The goals of the animal studies are to (i) Identify cellular mechanisms that lead to systemic and thrombogenic responses and associated cardiac events; (ii) Identify the particle sizes and chemical constituents that induce effects; (iii) Define pathways of direct UF/fine translocation to extrapulmonary sites; (iv) Evaluate the neurotoxic potential of UF/fine PM exposure; and (v) Analyze mechanistic pathways linking PM inhalation and deposition in the respiratory tract with effects at the portal of entry and in remote organs.
Description:
The Animal Core studies will help to answer the question of why subpopulations are at increased risk of adverse health outcomes following PM exposure. They will identify the cellular and molecular mechanisms which underlie cardiovascular susceptibility. Exposure-response relationships will be defined and we expect to learn how exposure duration, temporal variability in PM concentration and composition affect responses. Results of the animal studies, integrated with those of the epidemiological, controlled clinical, and in vitro studies, along with source-specific PM characterization and source apportionment analyses, will be used for correlating effects with specific PM constituents and sources.
Record Details:
Record Type:PROJECT(
ABSTRACT
)
Start Date:10/01/2005
Completion Date:09/30/2010
Record ID:
249276
Keywords:
RESPIRATORY TRACT, EXTRAPULMONARY ORGANS,
Related Organizations:
Role
:OWNER
Organization Name
:GSF-NATIONAL RESEARCH CENTER FOR ENVIRONMENT AND HEALTH
Organization Name
:RPCA
Role
:OWNER
Organization Name
:UNIVERSITY OF ROCHESTER
Organization Name
:RPCA
Project Information:
Approach
:The diabetic JCR rats will be used as a model of cardiovascular susceptibility to identify mechanisms of PM-induced thrombogenic events following acute and subchronic inhalation exposures to concentrated ambient UF/fine particles. Additional exposures of JCR rats to freshly-generated Diesel exhaust from a truck equipped with future (2007) filter trap technology will also be performed, using a mobile laboratory while driving on highways. Other animal studies will evaluate potential neurotoxic effects using a mouse model of neurodegeneration and subchronic exposures to ambient concentrated UF/fine particles. Particle size-dependent translocation pathways of inhaled UF/fine particles from the respiratory tract to extrapulmonary target tissues, including endothelial cells, blood platelets, bone marrow, heart, and CNS will also be examined. These studies are designed in close collaboration with the other Research Cores: information provided by the PM Characterization and Source Apportionment Research Core (Core 1) is an integral part of the animal studies, which are complementary to the epidemiological (Core 2) and controlled clinical studies (Core 3), and provide a link to the mechanistic in vitro studies (Core 5). In addition, this Core has strong collaborative ties to the Center's four Facility Cores: Biostatistics, Aerosol Generation and Analysis, Vascular and Inflammation, and Cardiac.
Cost
:$.00
Research Component
:Health Effects
Project IDs:
ID Code
:R832415C004
Project type
:Center