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

J. Silverberg*, D. Ginsburg, R. Orman, V. Amassian, H. G. Durkin, M. Stewart

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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+CD45Hi) and CD8+ (CD3+CD45Hi) T cell and CD45R+ (CD45Hi) 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.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalBrain, Behavior, and Immunity
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2010

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

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