title: c-FOS expression after hippocampal deep brain stimulation in normal rats.
abstract: OBJECTIVE
  We studied the effects of Hip-deep brain stimulation (DBS) on the expression of the inducible transcription factor c-FOS in the brain of normal rats.
  
  
  METHODS
  Ten Wistar rats were anesthetized, and nine were implanted with epidural and hippocampal electrodes for brain activity recording; one animal was used as sham. Bipolar stimulating electrodes were implanted in the left hippocampus. Three animals were used as control (implanted but not stimulated), one as sham (not implanted, not stimulated), and six as the study group. Stimulation was carried out using square wave pulses with 0.8V, 300 μsec, and 130 Hz (∼25μC/cm2) on the left hippocampus through the implanted bipolar hippocampal lead. Three animals were submitted to a one-hour and three to a six-hour stimulation session. Immunohistochemistry was employed to visualize c-FOS distribution in the rat's brain. The presence of seizures and electrocorticographic findings also were observed.
  
  
  RESULTS
  In animals submitted to both one-hour or six-hour unilateral hippocampal stimulation sessions, there was a significant bilateral overexpression of c-FOS in the hippocampus proper, dentate gyrus, and hylus. In the CA1 and CA3 regions, although activation was bilateral, c-FOS hyperexpression prevailed at the stimulated side over time; this was not true for the hilar and dentate gyrus regions where a more symmetric activation occurred over time. A significant c-FOS activation occurred after one hour of Hip-DBS in the ipsilateral amygdala; there was no contralateral amygdala activation, and by six hours, no amygdala activation was noted. No c-FOS activation was noted in other brain areas.
  
  
  CONCLUSIONS
  Our data showed that unilateral Hip-DBS was able to cause widespread and persistent bilateral activation of the normal rat limbic system, although in some, nuclei activation prevailed over the stimulated side. Cortical activation outside the limbic system was not noted. Our data represent a first approach to study the mechanistic paradigm involved in Hip-DBS.
authors.affiliation: Neurologia Experimental, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Jose C
authors.initials: JC
authors.lastname: da Silva
authors.forename: Fulvio A
authors.initials: FA
authors.lastname: Scorza
authors.forename: Mariana B
authors.initials: MB
authors.lastname: Nejm
authors.forename: Esper A
authors.initials: EA
authors.lastname: Cavalheiro
authors.forename: Arthur
authors.initials: A
authors.lastname: Cukiert
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D046690:Deep Brain Stimulation / Q000009:adverse effects; D018891:Dentate Gyrus / Q000378:metabolism*; D004567:Electrodes, Implanted; D005786:Gene Expression Regulation; D016762:Genes, fos; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos
keywords: c-FOS expression; hippocampal stimulation; rat