Role Of Microglia Activation And Expressed MRP8in The Development Of Mesial Temporal Lobe Epilepsy

Background:Mesial temporal lobe epilepsy (MTLE) is one of the most common refractory epilepsy. A growing number of studies showed a great role for inflammation in development of MTLE. Microglia cells are the immune cells of the central nervous system (CNS), which have immune surveillance effect in the brain, and involve in the development of multiple CNS diseases including epilepsy. Studies showed that activated microglia can express myeloid-related protein8(MRP8) which promotes brain inflammation. Till now there is no relevant data about the role of MRP8expressed from microglia in the development of MTLE.Objective:Firstly, to determine the activation of the microglia cells and expressional changes of MRP8in the process of MTLE development in the hippocampus. Secondly, confirm that MRP8expressed from activated microglia mediate the brain inflammation during MTLE development.Methods:1. Immature rat model of MTLE was induced by chloride lithium-pilocarpine. Immunohistochemical (IHC) method of CD11b/c (0X42) was used to detect microglia changes and real time polymerase chain reaction (real-time PCR) method was used to detect the expressional changes of MRP8in each group of rat hippocampus.2. Selected operation excision of MTLE patients’hippocampus and autopsy normal hippocampus, and detected MRP8expression in the two groups.3. Prepared rat microglia cells with primary culture method. The purity of cells was identified with OX42IHC method. Microglia cells were cultured under Oxygen/glucose deprivation (OGD) condition and cell viability was assessed by MTT (methylthiazol tetrazolium). MRP8expression was measured by real-time PCR after different OGD period.Results:1. In the seizure related acute and chronic stages of MTLE development the activated microglia significantly increased compared to normal control group (P<0.05), while in latent stage microglia didn’t activated obviously, MRP8was also upregulated in acute and chronic stages of MTLE which showed significant microglia activation.2. MRP8expression in patients with MTLE was significantly upregulated compared to control group (p<0.05).3. The purity of microglia cells was above95%. Furthermore, the viability of microglia cells increased slightly (p>0.05) after1min of OGD, obviously after5and10min of OGD (p<0.05), to be highest at10min.Then decreased significantly after longer times (15,30,45,60min) of OGD (p<0.05). The expression of MRP8in microglia cells first increased to reach the peak at10min (p>0.05), then decreased as the OGD time extended.Conclusions:Microglia activation induced MRP8expression in the hippocampus of MTLE and these are probability very important to the development of MTLE.