title: In Rasmussen encephalitis, hemichannels associated with microglial activation are linked to cortical pyramidal neuron coupling: a possible mechanism for cellular hyperexcitability.
abstract: OBJECTIVE
  Rasmussen encephalitis (RE) is a rare but devastating condition, mainly in children, characterized by sustained brain inflammation, atrophy of one cerebral hemisphere, epilepsy, and progressive cognitive deterioration. The etiology of RE-induced seizures associated with the inflammatory process remains unknown.
  
  
  METHODS
  Cortical tissue samples from children undergoing surgical resections for the treatment of RE (n = 16) and non-RE (n = 12) were compared using electrophysiological, morphological, and immunohistochemical techniques to examine neuronal properties and the relationship with microglial activation using the specific microglia/macrophage calcium-binding protein, IBA1 in conjunction with connexins and pannexin expression.
  
  
  RESULTS
  Compared with non-RE cases, pyramidal neurons from RE cases displayed increased cell capacitance and reduced input resistance. However, neuronal somatic areas were not increased in size. Instead, intracellular injection of biocytin led to increased dye coupling between neurons from RE cases. By Western blot, expression of IBA1 and pannexin was increased while connexin 32 was decreased in RE cases compared with non-RE cases. IBA1 immunostaining overlapped with pannexin and connexin 36 in RE cases.
  
  
  CONCLUSIONS
  In RE, these results support the notion that a possible mechanism for cellular hyperexcitability may be related to increased intercellular coupling from pannexin linked to increased microglial activation. Such findings suggest that a possible antiseizure treatment for RE may involve the use of gap junction blockers.
authors.affiliation: Intellectual and Developmental Disabilities Research Center, Brain Research Institute, Los Angeles, CA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.forename: Julia W
authors.initials: JW
authors.lastname: Chang
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Owens
authors.forename: My N
authors.initials: MN
authors.lastname: Huynh
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Chen
authors.forename: Conny
authors.initials: C
authors.lastname: Tran
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
authors.forename: Gary W
authors.initials: GW
authors.lastname: Mathern
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000293:Adolescent; D001703:Biophysics; D002135:Calcium-Binding Proteins; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D015331:Cohort Studies; D017630:Connexins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004558:Electric Stimulation; D004660:Encephalitis / Q000473:pathology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives; D008279:Magnetic Resonance Imaging; D008297:Male; D015767:Mefloquine / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D008840:Microfilament Proteins; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000502:physiology* / Q000503:physiopathology*
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D017630:Connexins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; C013411:biocytin; D008239:Lysine; D015767:Mefloquine
keywords: Gap junctions; Hyperexcitability; Pannexin; Rasmussen encephalitis