Investigators
in our group have shown that wound healing can be delayed through
behavioral modulation of immunity and inflammation. In this project,
the relationship between behavioral modulation, stress and wound
healing will be examined in context of spinal cord injury (SCI).
The goal is to develop an animal model that focuses on some common
features and mechanisms of stress — to permit a more thorough
evaluation of a broad range of stressor and psychological factors.
We have chosen a well-characterized model of SCI recently adapted
to the mouse in order to gain an understanding of how behavioral
influences affect immune responsiveness and wound healing. These
studies will examine two aspects of wound healing relevant to spinal
injured patients — repair of the injured spinal cord and healing
of peripheral tissue wounds (such as pressure sores).
The hypothesis for this proposal is that physical and psychological
stress associated with SCI will suppress inflammatory processes
resulting in delayed or incomplete wound healing of CNS and peripheral
tissue. To investigate this hypothesis, the following specific aims
will be undertaken: 1) To determine how SCI affects the fuctional
and neuroanatomical integrity of the hypothalamic-pituitary-adrenal
(HPA) and sympathetic-adrenal-medullary (SAM) axis in mice, 2) to
determine how cellular inflammation and cytokine-chemokine production
vary at the site of SCI, 3) to determine the effect of restraint
stress on HPA/SAM activation and the inflammatory response in SCI
in order to experimentally model the effect of psychological stress
associated with paralysis in human SCI patients, and 4) to determine
the capacity for tissue repair in the presence and absence of psychological
stress.
These studies will involve the participation of graduate students
and postdoctoral fellows. One graduate student has participated
extensively in the generation of preliminary data for the mouse
model of SCI and will be receiving a stipend for her role in this
project, which is an extension of her thesis work. Future graduate
students particularly in the Neuroscience Program will be able
to participate and learn first hand the physiological, psychological,
and immunological aspects of this work. In addition, fellows in
the PNI Postdoctoral Training Program will be encouraged to learn
about and participate in this project. For example, Connie Rogers,
Ph.D., is a postdoctoral fellow who joined Dr. Whitacre's laboratory
in January, 1999. She is supported by the PNI training grant
and will be involved in the design and conduct of the proposed
SCI studies.
back to top
|
