| Objective:Epilepsy is a disabling neurological disorder characterized by recurring, unprovoked seizures. Recent experimental and clinical evidences suggest that the immune system is involved in the etiopathogenesis of certain types of epilepsy. Dendritic cells (DCs) are the most important professional antigen presenting cells (APCs) which play a critical role in the generation of immune responses. Some studies suggested that DCs did accumulate in the CNS immune responses, such as the inflammation accompanying CNS injury or neurodegeneration, but little is known about epilepsy. In this study, to determine if DCs are involved in the immune response to epilepsy, we detected the DCs recruitment to the brain of epileptic patients and rats.Methods:1. From Apr to Oct 2010, the hippocampal tissues of epileptic patients was obtained after surgery in the department of neurosurgery, Xijing Hospital. Tissue sections were processed by immunofluorescence to detect CD11c+ dendritic cells(CD11c is a surface maker of dendritc cell).2. After lithium-pilocarione-induced seizures, all rats were sacrificed at different time-points (12h, 1d, 3d, 5d, 7d, 12d, 30d). By using immunohistochemistry, the distribution and time course of OX62+ dendritic cells were detected. The distribution of OX62 and Iba-1 were detected by double- label immunofluorescence (OX62 is another surface maker of dendritc cell).3. 60Co-ray irradiation (4Gy) was used on SD rats to destroy the DCs'peripheral sources--the hematopoietic stem cells and lymphocytes with the ability to differentiate into DCs in the bone marrow and peripheral blood. 3 days later, the number of peripheral blood lymphocytes were measured by tail vein blood smears MGG staining. Then, these rats were developed to lithium-pilocarione-induced seizures, epileptic rats were sacrificed at 1, 3d after SE. The distribution of OX62+ DCs were detected by immunohistochemistry.Results:1. In 3 of the 6 epileptic patients'brain tissues, CD11c + DCs were present in the hippocampus and cortex of temporal lobe. These cells with round cell bodies and 2-3 dendritices, scattered in the brain parenchyma.2. At 24h after Status Epilepticus, dendritic cells appeared in SD rats'brain, reaching peak numbers at 3-5d, but were no longer detected at 7 and 30 days. In the brain, the OX62+ DCs were identified in the cortex of temporal lobe and thalamus (lateral dorsal nucleus of thalamus, central lateral nucleus, anterodorsal nucleus of thalamus, lateral posterior nucleus of thalamus and posterior thalamic nuclei). No OX62+ DCs were detected in the brain of the control rats. There are no CD11c and Iba-1 double-labeled cells.3.The result of tail vein blood smears MGG staining, demonstrated that compared with the control group, peripheral blood lymphocytes number of 60Co radiation group reduced significantly(P<0.05). 1and 3d after lithium-pilocarione -induced SE, no OX62+ DCs were detected in the brain of epileptic rats.Conclusions:1. Recruitment of the dendritc cells to the brain of epileptic patients might serve as a starting point to investigate dendritic cells and immunity involved in human epileptogenesis and neuropathology in epilepsy.2. In our study, we firstly identified the distribution and time course of dendritic ccells in in acute phase of SE, and these DCs may be recruited from a blood-borne or peripheral precursor, but not a resident CNS population, such as microglia. These findings have lead to the suggestion that DCs may play a role in the pathogenesis of epilepsy. |
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