Splenic nerve bundle stimulation in acute and chronic inflammation

Splenic neurovascular bundle stimulation holds potential to treat acute and chronic inflammatory conditions. In the first part of the thesis, the available literature on the interactions between the immune system and nervous system in the intestine is summarized. Then, it is shown that a specialized T-cell, that can produce the neurotransmitter acetylcholine, resides in the gut an plays a dual role in the development of experimental colitis in mice. Furthermore, electrical splenic neurovascular bundle stimulation ameliorated the outcomes of colitis in mice and reversed transcriptomic changes in the gut that were induced by colitis. The second part of the thesis focused on the translation of splenic neurovascular bundle stimulation to the human situation. It is shown that there are significant changes between murine and human innervation of the spleen. Using computed tomography (CT) images the course and the characteristics of the splenic artery were described. These data were used to develop a cuff electrode that could be used for electrical stimulation of the splenic neurovascular bundle in humans. Finally, it was demonstrated that splenic neurovascular bundle stimulation in humans was safe and feasible in a pilot study with patients that underwent esophagectomy.