Possible mechanism of spinal T9 stimulation-induced acute renal failure: a virally mediatedtranssynaptic tracing study in transgenic mouse model.

The case report titled “Acute renal failure during a trial of spinal cord stimulation: Theories as to a possible connection” by Larkin et al (1) addressed that spinal T9 stimulation could lead to diminished renal blood flow by the decreased sympathetic input. Renal sympathetic innervation is widely acknowledged to involve the maintenance of fluid homeostasis and modulation of renal hemodynamics. The understanding of spinal cord segments innervating the kidney, and spinal sympathetic innervations and neuronal connections to the kidney is important for studying the possible mechanism of decreased renal sympathetic input during a trial of spinal T9 stimulation. We would like to further complete the discussion of Larkin and colleagues by introducing a virally mediated transsynaptic tracing study in a transgenic mouse model. The autonomic nervous system plays a prominent role in modulating carbohydrate metabolism (2). The kidneys respond to altered water and sodium availability with a set of homeostatic responses mediated by sympathetic outflow (3,4). The melanocortin-4 receptor (MC4R) is expressed in numerous spinal cord regions, and some findings indicated an important physiologic role for the MC4R in the regulation of renal sympathetic traffic by both leptin and insulin (5). We had characterized projections from the kidney to the spinal cord in adult male MC4R-green fluorescent protein (GFP) transgenic mice by using retrograde tracing techniques of pseudorabies virus (PRV) -614, expressing a novel monomeric red fluorescent protein (mRFP1) under control of the cytomegalovirus immediate early promoter, for direct visualization under a fluorescence microscope (6-10). We found that injections of PRV-614 into the kidney resulted in retrograde infection of neurons in the ipsilateral intermediolateral cell column (IML), the intercalates nucleus (IC), and the central autonomic nucleus (CAN) of the spinal cord, and PRV614-infecting cells were most heavily concentrated in the IML and were distributed sparsely in the IC and CAN of thoracic spinal cord segments T4 to L1, and most PRV-614 labeled cells specifically concentrated in the IML of T9 segment. Otherwise, PRV-614/ MC4R-GFP dual labeled neurons were detected in the IML and IC of the spinal cord (Fig. 1), and most PRV-614/MC4R-GFP labeled cells were found in the T9 segment (Fig. 2). Possible Mechanism of Spinal T9 StimulationInduced Acute Renal Failure: A Virally Mediated Transsynaptic Tracing Study in Transgenic Mouse Model