Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


osu1186411177.pdf (1.17 MB)

ETD Abstract Container

Abstract Header

Mechanisms of impaired humoral immunity after high thoracic spinal cord injury

Lucin, Kurt M
http://rave.ohiolink.edu/etdc/view?acc_num=osu1186411177

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Integrated Biomedical Science.
Individuals with spinal cord injury (SCI) are known to be highly susceptible to infection. This susceptibility is increased in individuals with high thoracic and cervical injuries. It has been widely speculated, but never proven, that dysfunctional sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis responses after SCI are involved in suppressing immunity. Normally, the HPA axis and SNS collaborate to ensure proper immune function, but this cross-talk requires an intact brain and spinal cord. Because HPA axis and SNS function are influenced by descending input from the brain, we hypothesized that high level SCI would cause greater dysfunction of the HPA axis and SNS and subsequently result in greater immunological impairment than lower level SCI. Using a mouse (C57BL/6) model of high thoracic (T3) SCI, we found dramatic dysfunction of the HPA axis and SNS, characterized by elevated serum corticosterone (CORT) and splenic norepinephrine (NE). In these mice, impaired neuroendocrine regulation was accompanied by robust humoral immune suppression; due in part to increased splenocyte apoptosis. Indeed, western blots for activated caspase-3 revealed an increase in splenic apoptosis after T3 SCI. Subsequent flow cytometry indicated that T and B lymphocytes and dendritic cells were all reduced within the spleen after T3 SCI. For all parameters measured, B cells were most affected. Splenic B cells were reduced ~75% at 3 days post-T3 SCI when compared to laminectomy control mice. This decrease in cell number was due in part to increased B cell apoptosis and involved an interaction between NE and CORT. Although in vitro and in vivo data revealed that CORT upregulates beta-2 adrenergic receptors (β2ARs) on B cells, a β2AR-mediated increase in intracellular 3'-5'-cyclic adenosine monophosphate (cAMP) was not sufficient to induce apoptosis. Instead, CORT and NE collaborate to elevate BIM (Bcl2-Interacting Mediator of Cell Death), a recently described pro-apoptotic molecule. Importantly, antagonizing CORT receptors diminishes BIM levels and reduces apoptosis. Taken together, these data provide mechanistic insight into immune suppression after high level SCI and identify HPA/SNS receptor antagonists as therapeutic candidates for restoring immune function or boosting vaccination responses after high thoracic SCI.
Phillip Popovich (Advisor)
153 p.
Spinal cord injury; Corticosterone; Norepinephrine; Antibody production; Spleen; Apoptosis

Recommended Citations

Citations

  • Lucin, K. M. (2007). Mechanisms of impaired humoral immunity after high thoracic spinal cord injury [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1186411177

    APA Style (7th edition)

  • Lucin, Kurt. Mechanisms of impaired humoral immunity after high thoracic spinal cord injury. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1186411177.

    MLA Style (8th edition)

  • Lucin, Kurt. "Mechanisms of impaired humoral immunity after high thoracic spinal cord injury." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1186411177

    Chicago Manual of Style (17th edition)

osu1186411177
1,007
© 2007, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.