RESUMEN
A new application of the photodynamic treatment (PDT) is presented for the opening of blood-brain barrier (BBB) and the brain clearing activation that is associated with it, including the use of gold nanoparticles as emerging photosensitizer carriers in PDT. The obtained results clearly demonstrate 2 pathways for the brain clearing: (1) using PDT-opening of BBB and intravenous injection of FITC-dextran we showed a clearance of this tracer via the meningeal lymphatic system in the subdural space; (2) using optical coherence tomography and intraparenchymal injection of gold nanorods, we observed their clearance through the exit gate of cerebral spinal fluid from the brain into the deep cervical lymph node, where the gold nanorods were accumulated. These data contribute to a better understanding of the cerebrovascular effects of PDT and shed light on mechanisms, underlying brain clearing after PDT-related opening of BBB, including clearance from nanoparticles as drug carriers.
Asunto(s)
Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de la radiación , Fotoquimioterapia , Animales , Transporte Biológico/efectos de la radiación , Barrera Hematoencefálica/diagnóstico por imagen , Barrera Hematoencefálica/efectos de los fármacos , Oro/química , Oro/metabolismo , Oro/farmacología , Sistema Linfático/efectos de los fármacos , Sistema Linfático/metabolismo , Sistema Linfático/efectos de la radiación , Masculino , Nanopartículas del Metal , Ratones , Permeabilidad/efectos de los fármacos , Permeabilidad/efectos de la radiación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/metabolismo , Fármacos Fotosensibilizantes/farmacología , Tomografía de Coherencia ÓpticaRESUMEN
We studied the level of blood oxygen saturation (SpO2) in the brain in newborn rats in the pre- and post-stroke periods, as well as the changes in cerebral blood flow and beta-arrestin-1 as a marker of hypoxic stress. Our results show that mild hypoxia precedes the stroke development and is associated with venous relaxation and decrease blood outflow from the brain resulting in the elevation of synthesis of beta-arrestin-1 in the brain. The incidence of stroke is characterized by severe hypoxia, which is accompanied by the progression of pathological changes in cerebral veins and the high level of beta-arrestin-1.
