Effect of T3 Spinal Contusion Injury on Upper Urinary Tract Function

Abstract

Spinal cord injury (SCI) significantly impacts many systems attributable to disrupted autonomic regulation of the body. Of these disruptions, excessive production/passage of urine (polyuria) has been understudied. Pre-clinical animal studies investigating SCI-induced polyuria have been carried out in T8-T10 spinal-level contusive injuries, which directly impacts both supraspinal sympathetic inputs to the spinal circuitry mediating kidney function as well as local networks including pre-ganglionic sympathetic fibers to the kidney. The current study utilizes a higher-level (T3) contusion to narrow the potential source(s) of damage that induce(s) polyuria. Metabolic cage 24-h urine collections demonstrated that, starting 1 week post-SCI and lasting chronically through 6 weeks post-SCI, T3 contused adult male rats had a significant increase in void volume relative to pre-injury and surgical sham controls. Subsequent examination of previously identified biomarkers revealed levels reflecting the presence of polyuria. For example, urine atrial natriuretic peptide levels were significantly increased at 6 weeks post-SCI compared to baseline, and serum arginine vasopressin (AVP) levels were significantly decreased. Further, there was a significant decrease post-injury relative to shams in the number of AVP-labeled cells within the suprachiasmatic nucleus, a hypothalamic region responsible for significant disruptions of circadian rhythmicity post-SCI, including loss of the diurnal variation of AVP production, which clinical studies have identified as contributing to the emergence of nocturia after SCI. Together, the current results demonstrate that SCI-induced polyuria is present after a T3-level SCI, indicating that damage of descending supraspinal circuitries precipitates dysfunction of homeostatic mechanisms involved in salt and water balance.

Keywords: hypothalamus; kidney; natriuretic peptides; polyuria; suprachiasmatic nucleus; vasopressin.

FIG. 1.

Metabolic cage data summary. Total 24-h urine volume output (left graph) demonstrates a statistically significant increase in urine production per passage at 1 wpi, lasting through 6 wpi, compared to pre-injury baseline volume and sham volumes. Total 24-h drink volume (right graph) indicates an absence of statistically significant changes in water intake across all time points relative to pre-injury and sham groups (*p < 0.05; T3 SCI, n = 11; sham, n = 6). SCI, spinal cord injury; wpi, weeks post-injury.

FIG. 2.

Suprachiasmatic nucleus (SCN) immunohistochemistry. A representative section showing AVP-labeled cells at 400 × in the SCN in both T3 sham and T3 SCI animals (A). In (B), a modified plate from the Rat Brain Atlas illustrates the location of the SCN within the hypothalamus. Average quantified AVP-labeled cells/μm in the SCN was statistically significantly lower in T3 SCI animals compared to sham controls (C; p < 0.05; T3 SCI, n = 5; T3 sham, n = 4). Values (shown in C) represent means; error bars represent standard error of means. AVP, arginine vasopressin; SCI, spinal cord injury.