Toll-like receptors -2 and -4 in the reactive gliosis propagation after traumatic brain injury

VERONICA MURTA; VANESA CADENA; ALEJANDRO VILLARREAL; ALBERTO JAVIER RAMOS; MARÍA BELÉN CIERI; GERARDO ROSCISZEWSKI

Córdoba

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Sociedad Argentina de Investigación en Neurociencias

Astrocytes respond to CNS injury with a process named reactive gliosis. It is still unknown how reactive gliosis rapidly propagates reaching very distant regions in the CNS after a focal brain injury. It is proposed that damage proteins released by dying neurons acting on TLR/NFκB pathway could be involved in the reactive gliosis propagation. To address this question, we here performed a penetrating traumatic brain injury by stab wound in wild-type (WT), TLR4KO and TLR2KO mice and used monolayer and 3D glial cells cultures. While stab-wounded WT animals showed a clear astrogliosis gradient at 3-7-14 days post-injury (DPI); TLR-deficient animals showed an exacerbated gradient of astrogliosis at 3-7 DPI. However, at 14 DPI, the TLR4KO animals showed a similar gradient to WT animals. At 3-7 DPI, microglial cells near to injury core showed an increased reactive phenotype in TLR-deficient animals compare to WT animals. In vitro, scratch wound produced a gradient of NFĸB activation in astroglial cultures, and the LPS exposure increased this gradient. Astroglial 3D cultures injected with TLR agonists LPS and HMGB1 responded with re-orientation of their process to the injected site in a dose-dependent manner. These results show that reactive gliosis propagation is a complex phenomenon that involves both astrocytes and microglia and that absence of TLR2 or TLR4 does not preclude reactive gliosis propagation, but affects it. Supported by grants PICT 2015-1451 and UBACYT.