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Academia Mexicana de Neurología, A.C.

2008, Número 5

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Rev Mex Neuroci 2008; 9 (5)


Barrera hematoencefálica. Nurobiología, implicaciones clínicas y efectos del estrés sobre su desarrollo

Escobar A, Gómez GB

Idioma: Español
Referencias bibliográficas: 91
Paginas: 395-405
Archivo PDF: 178.55 Kb.


RESUMEN

La barrera hematoencefálica (BHE ) es una estructura compleja constituida por células endoteliales de la red capilar del sistema nervioso central (SNC). Además, participan funcionalmente los pericitos, la lámina basal abluminal, los astrocitos perivasculares y la microglía. El endotelio de los capilares cerebrales se caracteriza porque cada borde celular está íntimamente unido a la célula adyacente que hace impermeable a la pared interna del capilar. En los mamíferos la BHE regula y restringe el acceso al parénquima nervioso de múltiples sustancias y moléculas que circulan en la sangre, para mantener la homeostasis del microambiente químico del SNC.
El sellado del endotelio se asocia a tres proteínas: claudina, ocludina y moléculas de adhesión de la unión, y a otras proteínas citoplasmáticas accesorias, tales como ZO1, ZO2, ZO3 y cingulina. La actina también participa. Las claudinas son importantes para la unión estrecha intercelular. Las claudinas – 1 y – 5 con la ocludina forman la BHE. La ocludina es una fosfoproteína. Las moléculas de adhesión de la unión pertenecen a las inmunoglobulinas; aunque hasta ahora no se sabe que papel desempeñan en la BHE.
Las funciones implícitas en la BHE son protección al cerebro y transporte selectivo de la red capilar al parénquima cerebral. La BHE es la estructura esencial de difusión en el SNC. Las sustancias atraviesan la BHE por: caveolas, transcitosis mediada por receptores, difusión transmembranal y mecanismos de acarreo y transportadores. También por vía retrógrada de flujo axónico.
Aunque la BHE parece implicar total impermeabilidad, en realidad posee características de permeabilidad selectiva, constituye en sí un tipo de filtro activo que regula el flujo por medio de sus elementos estructurales y metabólicos. El endotelio capilar es la estructura que restringe el paso de las moléculas hidrofílicas al tejido nervioso. Los componentes que regulan el intercambio son los transportadores y enzimas que dejan cruzar elementos esenciales, como aminoácidos, glucosa, transferrina y sustancias neuroactivas como neuromoduladores y sus análogos, sustancias liposolubles como alcohol y esteroides.
En el cerebro hay áreas desprovistas de BHE. La mayoría de esas áreas se hallan alrededor de los ventrículos cerebrales, lo cual justifica la designación de órganos circunventriculares: los plexos coroides, el órgano vasculoso de la lámina terminal, el órgano subfornical, el órgano subcomisural, la eminencia media, la glándula pineal, la neurohipófisis, y el área postrema. Esas áreas sin BHE permiten el libre intercambio bidireccional de moléculas sanguíneas con las neuronas del parénquima cerebral adyacente, y contribuyen a regular el sistema nervioso autónomo y las glándulas endocrinas.
Existen diversas condiciones neuropatológicas en las que se modifica el funcionamiento normal de la BHE, como hipoxia e isquemia. El estrés también constituye un factor importante que afecta el funcionamiento y desarrollo de la BHE; en el mamífero adulto el estrés agudo aumenta la permeabilidad de la BHE a macromoléculas circulantes en la sangre. Durante etapas tempranas del neurodesarrollo, el estrés altera la maduración de la BHE; en un modelo experimental en la rata se encontró que la exposición a estrés prenatal o postnatal aumentó la permeabilidad de la BHE al colorante azul de Evans en prácticamente todo el encéfalo.


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