Lymphocyte infiltration of neocortex and hippocampus after a single brief seizure in mice

作者：Silverberg J^*; Gin**urg D; Orman R; Amassian V; Durkin H G; Stewart M

来源：Brain, Behavior, and Immunity, 2010, 24(2): 263-272.

DOI：10.1016/j.bbi.2009.10.006

• Epilepsy
• Seizure
• Blood-brain barrier
• Maximal electric stimulation
• MES
• Neuroimmunology
• Microglia
• CD4
• CD8
• T cells
• B cells

Various immune responses have been described in epileptic patients and animal models of epilepsy, but immune responses in brain after a single seizure are poorly understood. We studied immune responses in brain after a single brief generalized tonic-clonic seizure in mice. C57bl/6 mice, either unanesthetized or anesthetized (pentobarbital, ethyl chloride) received either electrical (15-30 mA, 100 Hz, 1 s) or sham stimulation (subcutaneous electrodes over frontal lobe, no current). Electrical stimulation of unanesthetized mice resulted in tonic-clonic convulsions with hind-limb extension (maximal seizure), tonic-clonic convulsions without hind-limb extension (submaximal seizure), or no seizure. In contrast, such stimulation of anesthetized mice did not result in seizure. Mice were killed at 1 h-7 days after seizure. Brains or regions dissected from brain (neocortex, hippocampus, midbrain, cerebellum) of each group were pooled, single cell suspensions prepared, and cells separated according to density. CD4(+) (CD3(+)CD45(Hi)) and CD8(+) (CD3(+)CD45(Hi)) T cell and CD45R(+) (CD45(Hi)) B cell numbers were determined by flow cytometry. At 24 h after a maximal seizure, CD4(+) and CD8(+) T cells and CD45R(+) B cells appeared in brain, reaching peak numbers at 48 h, but were no longer detected at 7 days. CD4(+) T cells and CD45R(+) B cells were preferentially found in neocortex compared with hippocampus, whereas CD8(+) T cells were preferentially found in hippocampus at 24 h after a maximal seizure. In contrast, virtually no lymphocytes were detected in brains of unstimulated or sham stimulated mice, unanesthetized stimulated mice after submaximal or no seizure, and anesthetized stimulated mice at 1 h-7 day. Neither Ly6-G+ neutrophils nor erythrocytes were detected in brains of any animals, nor was there any detectable increase of blood-brain barrier permeability by uptake of Evans Blue dye. The results indicate that lymphocyte entry into brain after a single brief seizure is due to a selective process of recruitment into cortical regions.

• 出版日期2010-2