[Abstract Title]. - Society for Neuroscience

University of Cincinnati
Title: Development of a clinically relevant platform for the evaluation of the neuroprotective
effects of HF STN-DBS in parkinsonian rats
Authors: *A. SPIELES-ENGEMANN, M. M. BEHBEHANI, B. T. TERPSTRA, T. J.
COLLIER, K. STEECE-COLLIER, L. MADHAVAN, K. PAUMIER, S. WOHLGENANT, S.
GOMBASH, C. E. SORTWELL;
Univ. Cincinnati, Cincinnati, OH
Abstract: High-frequency deep brain stimulation of the subthalamic nucleus (HF STN-DBS) is
the most frequently practiced surgical therapy for treatment of Parkinson‟s disease (PD).
However, its clinical use has proceeded without a complete understanding of its mechanism of
action. Therefore, we set out to develop a rodent model that closely approximates its clinical
application in PD. To target the STN accurately and consistently, we utilized extracellular
microelectrode recordings to guide placement of the stimulator. Targeting was confirmed via dye
injections in the electrode trajectory and with Kluver-Barrera staining. To determine the volume
of tissue activated, we conducted dual stimulation-recording experiments with a stimulating
electrode placed in the STN and a recording electrode placed at varying distances away.
Recordings were made at each site before and after STN stimulation (130 Hz, 60 κs pulse width,
80-100 κA). Our studies indicate that STN-DBS at routine clinical parameters causes current
spread approximately 250 κm from the stimulator tip. Subsequently, stimulators were placed in
the anterior portion of the STN to minimize current spread to the SN. To establish a clinicallyrelevant
model of nigrostriatal dopamine denervation, a number of different lesion protocols
were tested using differing volumes of 6-hydroxydopamine (1-3 κl) injected into varying
locations in the striatum. Lesions were assessed via stereological counts of tyrosine hydroxylase
immunoreactive neurons in the substantia nigra (SN). The functional effects of lesioning were
assessed via the cylinder task. Our studies have identified a protocol that is similar to the clinical
presentation of Parkinson‟s disease in that it causes a progressive lesion (2 wk = 50% SN lesion,
4 wk = 70%, 6 wk = 75%) that generated significant deficits in forelimb akinesia and rotational
asymmetry. Finally, we lesioned animals with a progressive lesion protocol, implanted STN
stimulators utilizing extracellular microelectrode recordings, and stimulated animals for 2 weeks.
Placement of stimulators was confirmed histologically and functional effects of stimulation were
assessed via the cylinder task. Results of the long-term stimulation experiments revealed
functional improvement in forelimb akinesia and accurate long-term targeting of the STN. In
conclusion, these studies show that long-term stimulation of STN without substantial current
spread into the SN improves akinesia and indicates that the procedures we have developed can
be used for a reproducible, clinically-relevant long-term model of HF STN-DBS that has a wide
variety of applications.
Disclosures: A. Spieles-Engemann, None; M.M. Behbehani, None; B.T. Terpstra, None; T.J.
Collier, None; K. Steece-Collier, None; L. Madhavan, None; K. Paumier, None; S.
Wohlgenant, None; S. Gombash, None; C.E. Sortwell, None.