The candidate's focus is to investigate the mechanism of immune alteration in spinal cord injury (SCI) survivors and to determine the relationship between these immune alterations and infectious morbidity for two years following injury. Over the five years of the grant, the applicants will recruit 80 complete and incomplete SCI persons and 40 brain injury subjects with physical impairment as a comparison group. All subjects will be prospectively followed for a two-year period. Natural killer (NK) cell function will be assessed at baseline (4-8 months post injury), one year after baseline and two years after baseline. The mechanism of the immune alterations found in SCI will be investigated by examining the natural continuum of level and completeness of injury in the SCI group, as well as the physically impaired brain injury control group. The applicants will determine whether NK cell function is related to level/completeness of injury and/or physical impairment. The applicants will also group SCI subjects as (1) T6 and above and (2) below T6 to investigate the role of sympathetic derangement (present in the former but not the latter group) in the mechanism of NK alteration. Further the applicants will examine the role of bone marrow dysfunction by determining if there is loss of stem cells (progenitors of granulocytic-monocytic lineages [CFU-GM]) from bone marrow to the peripheral circulation. The applicants will collect data concerning numbers of urinary tract infections, upper respiratory tract infections, pneumonias, sepsis and rehospitalizations for two years to determine if these infectious events are inversely related to NK cell function, and related to CFU-GM. The hypotheses stated above will be tested utilizing regression analyses performed both within and across groups. The applicants postulate that the mechanism of immune alteration is sympathetic nervous system effects on the bone marrow stem cells. If correct, this information will define the target at which the applicants can aim their long-term research goal: the development of therapeutic interventions to improve immunity in persons with SCI.
| Marrie, R A; Rudick, R; Horwitz, R et al. (2010) Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology 74:1041-7 |
| Campagnolo, D I; Dixon, D; Schwartz, J et al. (2008) Altered innate immunity following spinal cord injury. Spinal Cord 46:477-81 |
