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Microglia and the immune response to a human temporal lobe seizure

ABSTRACT: Inflammatory processes and cells of the immune system including brain-resident microglia are activated in the epilepsies. We examined shape, transcriptomic profile and expression of microglial markers in tissue from the temporal lobe of epileptic patients. In the basal state, transcripts and pathways associated with the anti-inflammatory cytokine IL10, were up-regulated in the tissue from more sclerotic regions. We found that seizures also induce dynamic immune responses and change microglial phenotype. A pseudo-temporal ordering of the delay between the last seizure and tissue and analysis, based on immediate early gene expression, indicated an initial and local, innate immune response. At longer pseudo-time delays, infiltration of extra-cerebral cells, principally T-cells, contributed to the immune response. Ictal-like activity or ADP application in slices reproduced microglial activation including changes in motility and the liberation of inflammatory cytokines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94744 | GEO | 2022/03/18

REPOSITORIES: GEO

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Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples. Two color experiment

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Microglia and the immune response to a human temporal lobe seizure

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