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Project

Spinal Cord Injury Induced Polyuria

Funder: Craig H Neilsen Foundation

Funding period
USD 597 K
Funding amount
Abstract
Bladder dysfunction ranks among the top disorders affecting quality of life after spinal cord injury (SCI). The reduction in the cost to the health care system, care givers and society would be dramatic. Urological issues are responsible for many clinical complications post-SCI, including lifelong urologic care with repeated infections and many hospitalizations. Deficits include detrusor hyperreflexia, loss of bladder compliance, detrusor-sphincter dyssynergia and polyuria (overproduction of urine). Although polyuria is common after SCI and leads to more frequent bladder catheterizations and disruptions in sleep and daily activities, few studies have investigated the mechanisms underlying this condition and examined viable therapeutic options. Previous studies from our lab using adult male Wistar rats indicate the presence of polyuria with multiple lesion severities as early as 3 days post-injury that persists chronically (examined up to 11 weeks). One of the major hormones responsible for the regulation of water balance is arginine vasopressin (AVP; decreased levels leads to increased urine production). Very recent data from our lab demonstrates significantly increased urine output (polyuria) with a concomitant decrease in plasma AVP levels two weeks after a T9 spinal contusion injury (215 kdyn; adult male Wistar rats) relative to preinjury baseline levels. Urinalysis further revealed that the specific gravity and creatinine levels were significantly decreased at two weeks post-SCI, indicating that the urine was less concentrated. Importantly, despite the decrease in AVP levels, a change in blood osmolarity (the strongest stimulus that controls circulating AVP) was not the cause, suggesting that other factors are involved. The current study is designed to increase our understanding of the effect of SCI on polyuria (lesion level and severity, chronicity) and to examine potential underlying mechanisms including the regulation of AVP, the contribution of natriuretic peptides (sometimes referred to as the body’s “natural diuretics”), corticosterone (stress hormone that has indirect effects on AVP), as well as the benefit of intense exercise (known to increase AVP levels). A multi-disciplinary approach will include metabolic cage measurements, cystometry and assessing target tissues where AVP and natriuretic peptides are synthesized or have their site of action (kidney and hypothalamus). Targeting AVP, corticosterone and natriuretic peptides after SCI will likely provide novel therapeutic targets against polyuria and improve the quality of life for those in the SCI community. (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

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Urologic Diseases

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science