Intracranial electrode implantation produces regional neuroinflammation and memory deficits in rats
Deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD). The procedure entails intracranial implantation of an electrode in a specific brain structure followed by chronic stimulation. Although the beneficial effects of DBS on motor symptoms in PD are well known, it is often accompanied by cognitive impairments, the origin of which is not fully understood. To explore the possible contribution of the surgical procedure itself, we studied the effect of electrode implantation in the subthalamic nucleus (STN) on regional neuroinflammation and memory function in rats implanted bilaterally with stainless steel electrodes. Age-matched sham and intact rats were used as controls. Brains were removed 1 or 8 weeks post-implantation and processed for in vitro autoradiography with [(3)H]PK11195, an established marker of microglial activation. Memory function was assessed by the novel object recognition test (ORT) before surgery and 2 and 8 weeks after surgery. Electrode implantation produced region-dependent changes in ligand binding density in the implanted brains at 1 as well as 8 weeks post-implantation. Cortical regions showed more intense and widespread neuroinflammation than striatal or thalamic structures. Furthermore, implanted animals showed deficits in ORT performance 2 and 8 weeks post-implantation. Thus, electrode implantation resulted in a widespread and persistent neuroinflammation and sustained memory impairment. These results suggest that the insertion and continued presence of electrodes in the brain, even without stimulation, may lead to inflammation-mediated cognitive deficits in susceptible individuals, as observed in patients treated with DBS.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1014289
- Report Number(s):
- BNL-91371-2010-JA; EXNEAC; R&D Project: MO085; NIH RO1 NS050285; KP1602010; TRN: US201111%%242
- Journal Information:
- Experimental Neurology, Vol. 222, Issue 1; ISSN 0014-4886
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
60 APPLIED LIFE SCIENCES
ANIMALS
AUTORADIOGRAPHY
BRAIN
DISEASES
ELECTRODES
IN VITRO
MOTORS
ORIGIN
PATIENTS
PERFORMANCE
STAINLESS STEELS
STIMULATION
SURGERY
SYMPTOMS
Deep brain stimulation
brain injury
peripheral benzodiazepine receptor
translocator protein
autoradiography
novel object recognition
eletrode implantation
memory
rats