%0 Journal Article 
%A Perez-Caballero, Laura
%A Pérez- Egea, R.
%A Puigdemont, D.
%A Romero-Grimaldi, Carmen
%A Molet, J.
%A Caso, Javier R.
%A Micó Segura, Juan Antonio
%A Pérez, V
%A Berrocoso Domínguez, Esther María
%T Electrode implantation produces an early response to deep brain stimulation in depression: potential role of regional neuroinflammation.
%D 2013
%@ 0924-977X
%U http://hdl.handle.net/10498/38920
%X Background: Deep brain stimulation (DBS) is an increasingly
popular therapeutic non-pharmacological approach for diverse
neuropsychiatric diseases. Recent studies have shown promising
results 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 in
the severity of their symptoms right after surgery, followed by a
decay in the first month of treatment with DBS. Given that this
technique involves chronic implantation of electrodes in a specific
brain structure, this early response has been attributed a possible
placebo or to a physiological response to probe insertion in other
neurological diseases.
Purpose of the study: The aim of this study was to explore
the possible contribution of the surgical procedure itself in the
antidepressant response of DBS. Thus, we studied the effect of
electrode implantation in the rat medial prefrontal cortex (mPFC).
And additionally, the results were compared with the early outcome
of 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 the
infralimbic IL cortex (rodent SCG correlate) by the forced swimming
test (FST). The target area was processed to evaluate the
role of glial cells, the inflammatory mediators and the p11 implication
in the ‘insertional effect’. These changes were assessed by
immunohistochemical and western blot techniques. In addition,
we evaluated the early outcome of DBS in the SCG of 8 patients
with MDD involved in a clinical trial. Results were analyzed by
one or two-ways ANOVA followed by Bonferroni test. p<0.05
were considered to be significant.
Results: We found similar antidepressant-like effects in rats
implanted with electrodes, irrespective of whether they received
electrical brain stimulation or not, and this effect was via a main
action on serotonin neurotransmission. The ‘insertional effect’ was
due 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 mPFC
after electrode implantation. These behavioural and neurochemical
changes were blocked by anti-inflammatory drugs. On the other
hand, a retrospective study indicated that the early response of
MDD patients subjected to DBS was poorer when they received
anti-inflammatory drugs.
Conclusions: This study demonstrates that electrode implantation
up to the IL cortex is sufficient to produce benefits in animal
models of antidepressant activity. This ‘insertional effect’ could be
due to a regional neuroinflammation, and thus was blocked by the
treatment with anti-inflammatory drugs. These findings correlate
with the initial effects observed in a series of patients treated
for one month with DBS. Overall the results suggest that this
early antidepressant effect of DBS is the result of an inflammatory
‘insertional effect’ provoked by electrode implantation, in addition
to the electrical stimulation itself.
%K Deep brain stimulation (DBS)
%K depression
%~ Universidad de Cádiz