UNDERSTANDING THE SPATIO-TEMPORAL DISTRIBUTION OF REACTIVE ASTROCYTES AFTER FOCAL BRAIN INJURY AND THE ROLE OF TOLL-LIKE RECEPTOR SIGNALING

CIERI MB; INGRID M; VILLARREAL A; RAMOS AJ

Capital Federal

Congreso; Reunión anual de sociedades de biociencias 2021. Sociedad Argentina de Investigaciones Clínicas; 2021

Sociedad Argentina de Investigación Clínica (SAIC)

Astrocytes are essential homeostatic cells. However, reactive astrocytescan suffer a pathological remodeling that is detrimental forneuronal survival. We have previously shown that Toll-like receptors(TLR) pathway play a key role in the astroglial proinflammatoryphenotype induced by LPS. However; the spatio-temporal clues,the localization of pathologically remodeled astrocytes and whetherthe TLR/NFkB pathway is involved, are unknown facts. Using amodel of traumatic brain injury (TBI) by performing a cortical stabwoundlesion (2 mm posterior and lateral to Bregma; 1 mm depth)in C57BL/6 mice; we evaluated the spatio-temporal distribution ofsix GFAP+ astroglial phenotypes described by Sholl analysis. At1DPI astrocytes were similar to the non-injured hemisphere (type0, resting astrocytes), while highly hypertrophied astrocytes (typeV) significantly increased at 3-7DPI and were surrounded by degeneratingneurons with altered NeuN distribution. At longer recoverytimes (14-28DPI) type V population was reduced concomitantly withreduction of altered neurons. Microgliosis was also present, startingat 1DPI and peaking at 7DPI. Interestingly, decreased expression ofhomeostatic AQP4 channel was determined at 7DPI compared to3DPI. Also, we observed a decreased exploratory activity by openfield assay at 7DPI compared to 3DPI. Stimulation of TLR pathwayby administering LPS (5 mg/Kg i.p) resulted in a larger number oftype V astrocytes with a population of proinflammatory C3+ astrocytes,increased microgliosis associated with a decreased survivalneuronal at 7DPI. Loss of function achieved by administration of thechemical NFkB blocker sulfasalazine (150 mg/kg i.p) significantlyreduced astrogliosis, microgliosis, and neuronal death at 7DPI. Weconclude that an exacerbated astrogliosis is associated with neuronalimpairment and behavioral deficit and the TLR/NFkB pathwayis involved in this pathological astroglial conversion. Supported byPICT 2019-0851, UBACYT.