Abstract 15803: Thoracic Spinal Cord Stimulation Protects the Hippocampus in a Canine Model of Heart Failure
Background: Myocardial infarction (MI) and progression into heart failure (HF) is associated with pathological changes in the central nervous system. We previously demonstrated in a canine model of MI and mitral regurgitation (MR) that thoracic spinal cord stimulation (SCS) reduces mortality and preserves autonomic responsiveness for control of cardiac function. The purpose of this study was to evaluate potential protective effects of SCS in the brain in MI/MR.
Methods: Canines (n=14) underwent HF model creation involving sequential inductions of MI and MR; eight canines served as sham controls. MI/MR animals were randomized to two arms: “Control” with SCS OFF (N=8) and SCS (T1-T5, 50 Hz, 200 usec, 90% motor threshold) starting one week post MR induction (n=6). Both groups were maintained for 12 weeks post MI/MR induction. Autonomic status was evaluated for cardiac control prior to termination, after which brains were surgically removed. The hippocampus was isolated and evaluated using histochemistry (Nissl staining) and gene expression analysis of caspase-3 and e-NOS. Cell density in the dentate gyrus (DG) was assessed using ImageJ software to measure the area fraction of cell bodies using Nissl-stained sections.
Results: In MI/MR, Nissl staining revealed neuronal damage in all regions of the hippocampus and in the amygdala. In MI/MR, the area fraction within the DG was significantly reduced compared to sham control (reduced 19.8%, P= 0.003). Reactive SCS mitigated the neural damage in both brain regions and maintained cell density within the DG at levels equivalent to sham controls. Within the hippocampus, MI/MR was associated with increased mRNA levels of caspase-3 (increased 89.4%; P <0.0001) and eNOS (increased 98%; P= 0.006). MI/MR, with reactive SCS, was associated with caspase-3 mRNA in hippocampus maintained at sham control levels and eNOS mRNA levels reduced compared to the MI/MR expression level (36%, NS).
Conclusion: High thoracic SCS exerts neuro-protective effects within the hippocampus in the setting of chronic HF. Such SCS mediated neuro-protection may be manifested by decreasing apoptosis, reducing neuronal damage, and/or promoting neurogenesis in the DG.
- © 2013 by American Heart Association, Inc.