RT conference output
T1 Electrode implantation produces an early response to deep brain stimulation in depression: potential role of regional neuroinflammation.
A1 Perez-Caballero, Laura
A1 Pérez- Egea, R.
A1 Puigdemont, D.
A1 Romero-Grimaldi, Carmen
A1 Molet, J.
A1 Caso, Javier R.
A1 Micó Segura, Juan Antonio
A1 Pérez, V
A1 Berrocoso Domínguez, Esther María
A2 Psicología
K1 Deep brain stimulation (DBS)
K1 depression
AB Background: Deep brain stimulation (DBS) is an increasinglypopular therapeutic non-pharmacological approach for diverseneuropsychiatric diseases. Recent studies have shown promisingresults with the use of DBS in subgenual cingulated gyrus (SCG)for the treatment of refractory major depressive disorder (MDD).In these first clinical trials, the patients experience a reduction inthe severity of their symptoms right after surgery, followed by adecay in the first month of treatment with DBS. Given that thistechnique involves chronic implantation of electrodes in a specificbrain structure, this early response has been attributed a possibleplacebo or to a physiological response to probe insertion in otherneurological diseases.Purpose of the study: The aim of this study was to explorethe possible contribution of the surgical procedure itself in theantidepressant response of DBS. Thus, we studied the effect ofelectrode implantation in the rat medial prefrontal cortex (mPFC).And additionally, the results were compared with the early outcomeof a controlled clinical trial of DBS procedure in the SCG.Methods: Here we characterized the behavioural antidepressant-like effect of electrode implantation and DBS in theinfralimbic IL cortex (rodent SCG correlate) by the forced swimmingtest (FST). The target area was processed to evaluate therole of glial cells, the inflammatory mediators and the p11 implicationin the ‘insertional effect’. These changes were assessed byimmunohistochemical and western blot techniques. In addition,we evaluated the early outcome of DBS in the SCG of 8 patientswith MDD involved in a clinical trial. Results were analyzed byone or two-ways ANOVA followed by Bonferroni test. p<0.05were considered to be significant.Results: We found similar antidepressant-like effects in ratsimplanted with electrodes, irrespective of whether they receivedelectrical brain stimulation or not, and this effect was via a mainaction on serotonin neurotransmission. The ‘insertional effect’ wasdue to a temporally neuroinflammation, and it was correlated with an increase of glial-fibrillary-acidic-protein immunoreactivity. Additionally,neuronal p11 expression and IL-1b, COX1, COX2,TNFa, as inflammatory mediators, were increased in the mPFCafter electrode implantation. These behavioural and neurochemicalchanges were blocked by anti-inflammatory drugs. On the otherhand, a retrospective study indicated that the early response ofMDD patients subjected to DBS was poorer when they receivedanti-inflammatory drugs.Conclusions: This study demonstrates that electrode implantationup to the IL cortex is sufficient to produce benefits in animalmodels of antidepressant activity. This ‘insertional effect’ could bedue to a regional neuroinflammation, and thus was blocked by thetreatment with anti-inflammatory drugs. These findings correlatewith the initial effects observed in a series of patients treatedfor one month with DBS. Overall the results suggest that thisearly antidepressant effect of DBS is the result of an inflammatory‘insertional effect’ provoked by electrode implantation, in additionto the electrical stimulation itself.
PB Elsevier
SN 0924-977X
YR 2013
FD 2013
LK http://hdl.handle.net/10498/38920
UL http://hdl.handle.net/10498/38920
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026