title: Long-term stimulation of the subthalamic nucleus in hemiparkinsonian rats: neuroprotection of dopaminergic neurons.
abstract: OBJECTIVE
  The goal of this study was to evaluate the neuroprotective effects conferred by long-term electrical stimulation of the subthalamic nucleus (STN) against degeneration of dopaminergic neurons by assessing motor functional and immunohistological findings in hemiparkinsonian rats.
  
  
  METHODS
  In 13 of 25 rats, a concentric microelectrode was stereotactically implanted into the right STN under the guidance of extracellular microelectrode recording. After this had been done the animals were given an injection of 6-hydroxydopamine (6-OHDA) into the right striatum. Seven of the rats received continuous stimulation (frequency 130 Hz, intensity 80-100 microA) for 2 weeks (Group A); the other six did not receive any stimulation during this period (Group B). Twelve rats did not receive electrode implantation and underwent 6-OHDA injection only; these animals served as a control group (Group C). After 2 weeks, motor function in the rats was evaluated by conducting an amphetamine-induced rotation test. Finally, tyrosine hydroxylase-immunoreactive neurons in the pars compacta of the substantia nigra (SNc) were counted to evaluate the extent of degeneration of dopaminergic neurons. Ipsilateral rotation was significantly decreased in Group A, regardless of the effects of stimulation delivered during the test (p < 0.05). Rats in Group B demonstrated typical circling as did those in Group C, except that on stimulation Group B rats immediately stopped circling or changed direction. Tyrosine hydroxylase-immunoreactive neurons in the SNc were significantly preserved in the animals in Group A, whereas neurons in animals in Groups B and C were moderately depleted (p < 0.01).
  
  
  CONCLUSIONS
  Acutely, STN stimulation improved rotation symmetry in rats with moderate SNc degeneration. When STN stimulation had been applied for the preceding 2 weeks, motor function was better and SNc neural degeneration was significantly milder. Subthalamic nucleus stimulation thus appears to protect dopaminergic neurons in this hemiparkinsonian model, in addition to improving motor function in these animals.
authors.affiliation: Department of Neurosurgery and Pathology of Biological Response, Nagoya University School of Medicine, Japan. maesawa@med.nagoya-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maesawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kaneoke
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Kajita
authors.forename: Naotaka
authors.initials: N
authors.lastname: Usui
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Misawa
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakayama
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy; D006801:Humans; D009048:Motor Skills; D009474:Neurons / Q000473:pathology; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy* / Q000662:veterinary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000502:physiology*
chemical_list: D018663:Adrenergic Agents; D011954:Receptors, Dopamine; D016627:Oxidopamine