Fig. 7

Representative graphical image presenting the underlying mechanism of glutamate-induced excitotoxicity and how B-TCE pretreatment protects primary cerebellar neurons by modulating the expression of different molecular effectors. Overstimulation of glutamate receptors induced rise in intracellular calcium which leads to mitochondrial dysfunction and activation of enzymes which further results in ROS/RNS generation and structural degradation of neurons. ROS/RNS induce upregulation of inflammatory mediators, DNA damage and stress chaperones thus causing apoptosis and neurodegeneration. In the present study B-TCE pretreatment inhibited glutamate-induced structural degradation (morphometric studies, MAP-2, GAP-43, NF200), mitochondrial dysfunction (Mitotracker green FM), suppressed NO generation (iNOS), secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), DNA damage (Cyclin D1 and PCNA) and stress proteins expression (HSP70 and Mortalin), thus inhibited apoptosis induction and neurodegeneration. B-TCE also promoted neuronal plasticity and migration (PSA-NCAM, NCAM expression)