Impact of Cervical Lymphatic Obstruction on Brain Pathophysiology in Cervical Lymphedema Animal Models

Abstract

ABSTRACTBackgroundInjury to the cervical lymph nodes can lead to cervical lymphedema and subsequent fluid accumulation in the head and neck region, potentially causing pathophysiological alteration in the brain. This condition is thought to be linked with various neurological diseases, although the direct connection between cervical lymphatic obstruction and its effect on the brain has been difficult to establish.MethodsWe produced the disease animal models through lymph node dissection and radiation in fifteen male Sprague–Dawley rats aged 8 weeks and weighing 280–320 g. The models were specifically designed to induce lymphatic obstruction in the cervical region only, with no direct interventions applied to the brain. We evaluated swelling and lymphatic drainage in the head and neck for follow-up. The size of the lateral ventricles was verified through MRI, and changes in water content in brain tissue were directly measured. At 2 and 8 weeks, we observed immune cell infiltration, ventricular enlargement, and pathohistological changes in the harvested brain tissues.ResultsThe experimental animals exhibited lymphatic obstruction in the cervical region, with swelling, abnormal lymphatic drainage, and immune cell infiltration into the brain’s white matter, reminiscent of extremities lymphedema. MRI revealed lateral ventricular enlargement in these animals, indicative of increased cerebrospinal fluid levels compared to the control group. This increase in cerebrospinal fluid was associated with an increase in brain tissue water content, leading to pathophysiological changes akin to those seen in hydrocephalus and cerebral edema.ConclusionThe outcomes in this study underscore a significant link between lymphatic circulatory dysfunction and the onset of neurophysiological diseases. Cervical lymphedema showed pathophysiological changes similar to those seen in extremities lymphedema. However, these changes in the brain could be more critical than in the extremities. Our finding highlights the importance of understanding lymphatic system health in preventing and managing neurological conditions.