![]() We did not count LYVE-1 or Ki67 single-positive cells to exclude potential signal from the macrophage population. Deep and superficial CLNs were collected and analyzed by immunohistochemistry. b– d Male SD rats were subjected to 100 min of transient focal cerebral ischemia. Within 30 min, Evans Blue fluorescence was detected in deep and superficial cervical lymph nodes (CLNs) but not in axillary lymph nodes (ALNs) or inguinal lymph nodes (ILNs). These findings suggest that modulating the brain-to-CLN pathway may offer therapeutic opportunities to ameliorate systemic inflammation and brain injury after stroke.Ĭervical lymph node activation in rats after stroke: a Evans Blue dye (2%, 10 µL) was injected into lateral ventricles in normal male Sprague Dawley (SD) rats. Lastly, surgical removal of CLNs in mice significantly reduces infarction after focal cerebral ischemia. In vitro, VEGF-C/VEGFR3 signalling in lymphatic endothelial cells enhances inflammatory responses in co-cultured macrophages. Blockade of VEGFR3 reduces lymphatic endothelial activation, decreases pro-inflammatory macrophages, and reduces brain infarction. Microarray analyses of isolated lymphatic endothelium from CLNs of ischemic mice confirm the activation of transmembrane tyrosine kinase pathways. In rats subjected to focal cerebral ischemia, lymphatic endothelial cells proliferate and macrophages are rapidly activated in CLNs within 24 h, in part via VEGF-C/VEGFR3 signalling. Here we show that a brain-to-cervical lymph node (CLN) pathway is involved. PMC articleĪfter stroke, peripheral immune cells are activated and these systemic responses may amplify brain damage, but how the injured brain sends out signals to trigger systemic inflammation remains unclear. 6 Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. 5 Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.4 Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, Singapore.3 Department of Emergency and Critical Care Medicine, Fukuoka University Hospital, Jonan, Fukuoka, Japan.2 China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.1 Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
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