Microglia phenotype in temporal lobe epilepsy (MICROGLIA-EPILEPSY)
Microglia phenotype in temporal lobe epilepsy
Date du début: 1 avr. 2014,
Date de fin: 31 mars 2016
Microglia are the primary immune cells of the central nervous system (CNS) and are considered potential key players in the pathophysiology of temporal lobe epilepsy (TLE). Indeed, microglia activation is observed directly after status epilepticus and during epileptogenesis, both in TLE animal models as well as in human patients. Since microglia activation is correlated with the presence of pro-inflammatory factors, they are considered to be harmful. Recent findings, however, suggest that inflammation is a prerequisite to promote repair processes and that local microglia support cell survival and tissue repair. Moreover, TLE is also characterized by a massive infiltration of peripheral immune cells, including macrophages. Since it is impossible to differentiate microglia from invading macrophages in situ, the detrimental role attributed to microglia might be incorrect.We have recently developed a method to acutely isolate microglia/macrophages from mouse tissue and to subsequently discriminate microglia from macrophages using FACS sorting. In this research project, we propose to apply this method to further characterize the phenotype of microglia and compare it with that of infiltrating macrophages at various time points during the epileptogenesis phase of TLE. Using qPCR, flow cytometry and immunohistochemistry analysis, we will examine the expression of well-established phenotype markers for inflammation and supportive functions in a model of TLE and in human brain tissue. We hypothesise that a supportive role of microglia towards brain repair could pertain during epileptogenesis whereas infiltrating proinflammatory macrophages mediate devastating activity.The data that will be derived from this study will permit to better understand the role of microglia in TLE and may provide new therapeutic targets to amplify endogenous repair mechanisms.
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