Damage associated protein HMGB1 play a key role in the neuroinflammation and neurodegeneration that follows status epilepticus

SARCHI P ; AUZMENDI JA ; RAMOS AJ

BUENOS AIRES

Congreso; 2° Reunión Conjunta de Biociencias.; 2017

High-mobility group box-1 (HMGB1) is a DAMP released after brain injury that activates localmicroglia and astrocytes but also behaves as long-range cytokine acting on the professionalimmune organs. Activated (reactive) astrocytes, can secrete molecules such asThrombospondin-1 (TSP-1) that induce excitatory synapses and thus could have a major role inthe altered excitatory/inhibitory balance that is the biological substrate of epileptogenesis.However, HMGB1 role in epileptogenesis is still unclear. For that purpose, status epilepticus (SE)was induced on 300 g Wistar rats by lithium chloride plus pilocarpine treatment (127 mg/kg and 30mg/kg respectively) and stopped with 20 mg/kg diazepam after 20 min of SE. Then, we blocked thesignalling of HMGB-1 applying glycyrrhizin (GLY) 333 mg/kg (i.p) twice a day for four days. Toevaluate the expression of synaptogenic molecule TSP-1, in vitro studies were performed onglial mix cultures or enriched astrocytes cultures. Both types of culture were stimulated withrecombinant HMGB-1 (500 ng/ml) and TSP-1 expression was determined byimmunofluorescence. In vivo, we found that GLY treatment significantly reduced both reactivegliosis and neuronal death in cortex and hippocampus (one-way ANOVA p