title: Effects of intrathecal baclofen therapy on motor and cognitive functions in a rat model of cerebral palsy.
abstract: OBJECTIVE
  Cerebral palsy (CP) arises in the early stages of brain development and manifests as spastic paresis that is often associated with cognitive dysfunction. Available CP treatments are aimed at the management of spasticity and include botulinum toxin administration, selective dorsal rhizotomy, and intrathecal baclofen (ITB). In this study, the authors investigated whether the management of spasticity with ITB therapy affected motor function and whether the release of spasticity was associated with an improvement in intellectual function.
  
  
  METHODS
  Newborn Sprague-Dawley rats were divided into the following groups: control, CP model, and CP model with ITB therapy. For the CP model, postnatal Day 7 (P7) rats were exposed to hypoxic conditions (8% O(2)) for 150 minutes after ligation of the right common carotid artery. In the groups receiving ITB therapy, a spinal catheter was connected to an osmotic pump filled with baclofen and placed in the spinal subarachnoid space on P21 in the early group and on P35 in the late group. A daily dose of 12 μg of baclofen was continuously administered until P49, resulting in 28 days of therapy in the early group and 14 days in the late group. Changes in spasticity in the CP and CP with ITB treatment groups were confirmed by assessing the motor evoked potential in the plantar muscle.
  
  
  RESULTS
  In the CP group, the time required to complete a beam-walking test on P49 was significantly longer than that in the control and ITB treatment groups (4.15 ± 0.60 vs 2.10 ± 0.18 and 2.22 ± 0.22 seconds, respectively). Results of the beam-walking test are expressed as the mean ± SD. Radial arm maze performance on P49 indicated that spatial reference memory had significantly deteriorated in the CP group compared with controls (2.33 ± 0.87 vs 0.86 ± 0.90 points); moreover, working memory was also negatively affected by CP (0.78 ± 1.09 vs 0.14 ± 0.38 points). Results of the memory tests are expressed as the mean ± SE. These memory functions did not recover after ITB treatment.
  
  
  CONCLUSIONS
  Management of spasticity with ITB therapy improved the walking ability in the rat CP model. Intrathecal baclofen therapy-which reduces harmful sensory and motor stimulations caused by spasticity to more optimal levels-contributed to motor function recovery; however, it had no effect on intellectual recovery as assessed by memory performance in the rat CP model.
authors.affiliation: Department of Neurosurgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. snomura@yamaguchi-u.ac.jp
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Nomura
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kida
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Maruta
authors.forename: Hirochika
authors.initials: H
authors.lastname: Imoto
authors.forename: Masami
authors.initials: M
authors.lastname: Fujii
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001418:Baclofen / Q000008:administration & dosage / Q000627:therapeutic use*; D002547:Cerebral Palsy / Q000150:complications*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D004558:Electric Stimulation; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000473:pathology; D007278:Injections, Spinal; D018782:Maze Learning; D008570:Memory, Short-Term / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology; D019635:Neurosurgical Procedures; D004856:Postural Balance / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013979:Tibial Nerve / Q000502:physiology
chemical_list: D018755:GABA Agonists; D001418:Baclofen