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Project

Elucidation of Mechanisms Behind Renal Dysfunction After Spinal Cord Injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
SCI affects the entire body to greatly impact overall health. For instance, people with SCI are significantly more prone to renal dysfunction. However, how SCI affects kidney function is a vastly understudied topic. Thus, there is a significant gap in our understanding of renal dysfunction after SCI. Elucidating the mechanistic underpinnings of renal damage after SCI is crucial to understanding the pathogenesis of chronic kidney disease after SCI and will inform therapeutic strategies. High-level SCI results in a hyperexcited spinal sympathetic circuit that detrimentally impacts organs that receive sympathetic output. Another consequence a hyperexcited spinal sympathetic circuit after a high-level SCI is both hypotension and periods of extreme hypertension associated with autonomic dysreflexia. Additionally, high-level SCI results in maladaptive remodeling of vascular smooth muscle cells such that they have increased sensitivity to vasopressors and periods of spontaneous oscillations, likely mediated by calcium signaling and contributing to the periods of hypertension. We hypothesize that renal dysfunction is more severe following high-level SCI than low-level SCI. We also hypothesize that SCI-induced renal dysfunction is exacerbated by aberrant heterotrimeric G protein signaling (e.g., Gq/11 class G proteins) in vascular smooth muscle cells, which is known to contribute to blood pressure dysregulation in other disease models. In Aim 1, we will determine if high-level SCI results in more severe renal dysfunction than low-level SCI. In Aim 2, we will examine if pharmacologically inhibiting Gq/11 attenuates SCI-induced renal dysfunction. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1103 Clinical Sciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Cardiovascular

  • RCDC

    Hypertension

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Kidney Disease

  • RCDC

    Neurodegenerative

  • HRCS HC

    Cardiovascular

  • HRCS HC

    Renal and Urogenital

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science