Abstract WP414: Transcranial Photobiomodulation of Clearance of Blood Products From the Neonatal Brain via the Meningeal Lymphatics

Abstract

In human data we observed the presence of products of degraded blood (the iron/hemosiderin) in the meningeal lymphatic vessels (MLVs) and in the deep cervical lymph node (dcLN) in newborns who died after intracranial hemorrhages. Here we demonstrate novel data related to transcranial photobiomodulation (tPBM) of clearance of blood products (the iron/hemosiderin) from the brain via MLVs in newborn rats after stress-induced intracranial hemorrhages (SIH). Experiments were carried out in 73 newborn rats (5 g) with SIH. All procedures were performed in accordance with the “Position of the American Heart Association on Research Animal Use” (Circulation 1985; 71:849A). The new generation laser 1268 nm (30 nm, 7 min) was used for tPBM of lymphatic clearance of blood products that was analyzed in vivo (two-photon, fluorescent, optical coherent tomography imaging) and ex vivo (immunohistochemical, confocal data) using markers of cerebral and lymphatic endothelium (CD31, LYVE-1/LYVE-1 conjugated with Alexa 488 and Prox-1). The results clearly demonstrated that 30 min after SIH the iron/hemosiderin (detected by atomic absorption spectroscopy and histological method) accumulated in the dcLN and observed in the MLVs. The tPBM caused stimulation of lymphatic drainage function that was accompanied by decrease in the iron/hemosiderin level in the brain tissues with an appropriate increase of their level in the dcLN. The tPBM (one time a day) during one week contributed a better recovery after SIH vs. the control group (without tPBM) that was confirmed by analysis of inflammatory factors (C-reactive protein, IL-6 and lipoprotein-associated phospholipase A2, immunoassay analysis), macrophages infiltration (confocal imaging), edema, necrotic and ischemic events (histological data). In sum, our results suggest that tPBM by stimulation of endogenous processes of cerebral lymphatic drainage and clearing function might be a novel non-invasive approach for brain recovery after neonatal intracranial hemorrhages. The research was supported by grant of Russian Science Foundation No 18-75-10033.