Nerve damage can cause chronic, debilitating problems including loss of motor control and paresthesia, and generates maladaptive neuroplasticity as central networks attempt to compensate for the loss of peripheral connectivity. However, it remains unclear if this is a critical feature responsible for the expression of symptoms. Here, we use brief bursts of closed-loop vagus nerve stimulation (CL-VNS) delivered during rehabilitation to reverse the aberrant central plasticity resulting from forelimb nerve transection. CL-VNS therapy drives extensive synaptic reorganization in central networks paralleled by improved sensorimotor recovery without any observable changes in the nerve or muscle. Depleting cortical acetylcholine blocks the plasticity-enhancing effects of CL-VNS and consequently eliminates recovery, indicating a critical role for brain circuits in recovery. These findings demonstrate that manipulations to enhance central plasticity can improve sensorimotor recovery and define CL-VNS as a readily translatable therapy to restore function after nerve damage.
Severe pulmonary hypertension and severe tricuspid regurgitation are often considered strict contraindications for orthotopic liver transplantation. A combined approach of tricuspid repair and subsequent liver transplantation could provide a novel approach for patients with severe pulmonary hypertension and tricuspid regurgitation to undergo orthotopic liver transplantation. A 62-yearold male with a history of end-stage renal disease on hemodialysis, cirrhosis, and third-degree atrioventricular heart block status post single lead pacemaker insertion presented for an orthotopic liver transplant. However, after placement of a Swan-Ganz catheter by the anesthesia team, the patient's central venous pressure was found to be high, and his mean pulmonary artery pressure was 40 mmHg. His case was canceled due to concern for poor postoperative outcomes after a subsequent transesophageal echocardiogram revealed a severely dilated right heart and 4+ tricuspid regurgitation with flow reversal into the hepatic veins. After discussion among the hospital's transplant committee, the patient was planned to have a tricuspid valve repair, liver transplant, and kidney transplant surgery several months later. The patient successfully underwent tricuspid valve repair and orthotopic liver transplant and then kidney transplant the following day.
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