Activation Of Glia In Rat Excitotoxic Model And Its Relationship With NF-κB Signaling Pathway

Aim: To study the activation of microglial and its role in excitotoxicity mediated by NMDA receptors.Methods: Rat model of excitotoxicity was produced with stereotaxic administration of quinolinic acid into unilateral striatum, the damage of striatal neurons of the rat was assessed with Cresyl violet staining, the activation of microglial was observed with immunohistochemistry of CD11b, Western blot analysis of degradation of IκB-αand increases in the protein levels of Fas-L and the nuclear translocation of NF-κB in the injected striatum. The expression of CD40 mRNA and NF-κB target gene p53 mRNA was assessed with Real-Time PCR.Results: After QA was injected into the corpus striatum, activation of microglia was observed in a time-dependent manner with immunohistochemistry, and peaked 24 h after QA administration. The expressions of TNF-αand FasL detected by Western Blot significantly increased. The expression of CD40 detected by the Real-Time PCR increased significantly, while Western Blot analysis showed that the levels of NF-κB inhibitor protein IκB-αdecreased. Immunofluorescence revealed increased nuclear translocation of NF-κB,. Real-Time PCR showed that the expression of p53 significantly increased. Nissl staining indicated that inhibiting the activity of NF-κB can protect neurons against QA-induced excitotoxicity.Conclusion: The NMDA-mediated excitotoxicity can cause the activation of microglial, release of cell factors related to inflammation. QA also activate the NF-κB signaling pathway, thus leading to the expression of down-stream genes related to apoptosis and causing the injuries of neurons.