Toll-Like Receptors 2 and 4 in the Reactive Gliosis Propagation After Traumatic Brain Injury

CIERI MB, ; MURTA V, ; CADENA V, ; ROSCISZEWSKI G, ; VILLARREAL A,; RAMOS AJ

Cordoba

Congreso; Reunion Anual de la Sociedad Argentina de Investigacion en Neurociencias 2018; 2018

Sociedad Argentina de Investigación en Neurociencias

Astrocytes respond to CNS injury with a process namedreactive gliosis. It is still unknown how reactive gliosis rapidlypropagates reaching very distant regions in the CNS after afocal brain injury. It is proposed that damage proteinsreleased by dying neurons acting on TLR/NFjB pathwaycould be involved in the reactive gliosis propagation. Toaddress this question, we here performed a penetratingtraumatic brain injury by stab wound in wild-type (WT),TLR4KO, and TLR2KO mice and used monolayer and 3Dglial cells cultures. While stab-wounded WTanimals showeda clear astrogliosis gradient at 3 to 7 to 14 days post-injury(DPI); TLR-deficient animals showed an exacerbated gradientof astrogliosis at 3 to 7 DPI. However, at 14 DPI, theTLR4KO animals showed a similar gradient to WT animals.At 3 to 7 DPI, microglial cells near to injury core showed anincreased reactive phenotype in TLR-deficient animals compareto WT animals. In vitro, scratch wound produced a gradientof NFOEB activation in astroglial cultures, and the LPSexposure increased this gradient. Astroglial 3D culturesinjected with TLR agonists LPS and HMGB1 respondedwith re-orientation of their process to the injected site ina dose-dependent manner. These results show that reactivegliosis propagation is a complex phenomenon that involvesboth astrocytes and microglia and that absence of TLR2 orTLR4 does not preclude reactive gliosis propagation butaffects it.This study was supported by grants PICT 2015-1451and UBACYT.