title: Beneficial effects of minocycline and botulinum toxin-induced constraint physical therapy following experimental traumatic brain injury.
abstract: BACKGROUND
  Effective recovery from functional impairments caused by traumatic brain injury (TBI) requires appropriate rehabilitation therapy. Multiple pathways are involved in secondary injury and recovery suggesting a role for multimodal approaches.
  
  
  OBJECTIVE
  Here, we examined the efficacy of the anti-inflammatory agent minocycline and botulinum toxin (botox)-induced limb constraint with structured physical therapy, delivered alone or in combination, after a severe TBI produced by a controlled cortical impact in rats.
  
  
  METHODS
  Minocycline was administered at 25 mg/kg daily for 2 weeks beginning 1 day after TBI or sham surgery. For constraint/physical therapy, botox-type A was injected into the nonaffected forearm muscle 1 day after injury and 2 weeks of physical therapy commenced at 5 days after injury. Functional evaluations were conducted 8 weeks after injury.
  
  
  RESULTS
  Minocycline, either as a monotherapy or as combination treatment with botox/physical therapy significantly reduced impairments of spatial learning and memory in the water maze test, whereas botox/physical therapy reduced forelimb motor asymmetry and improved manual dexterity in the cylinder and vermicelli handling tests, A synergistic effect between the 2 treatments was observed when rats performed tasks requiring dexterity. Inflammation was attenuated in the peri-contusion cortex and hippocampus in all TBI groups receiving mono or combination therapies, though there was no significant difference in lesion size among groups.
  
  
  CONCLUSIONS
  These data provide a rationale for incorporating anti-inflammatory treatment during rehabilitation therapy.
authors.affiliation: 1San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Tina I
authors.initials: TI
authors.lastname: Lam
authors.forename: Deborah
authors.initials: D
authors.lastname: Bingham
authors.forename: Ting Ju
authors.initials: TJ
authors.lastname: Chang
authors.forename: Chih Cheng
authors.initials: CC
authors.lastname: Lee
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.forename: Dongmin
authors.initials: D
authors.lastname: Wang
authors.forename: Stephen
authors.initials: S
authors.lastname: Massa
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Swanson
authors.forename: Jialing
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000502:physiology; D008911:Minocycline / Q000627:therapeutic use*; D026741:Physical Therapy Modalities; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019274:Botulinum Toxins, Type A; D008911:Minocycline
keywords: botox; constraint-induced movement therapy (CIMT); controlled cortical impact; glial fibrillary acidic protein (GFAP); microglia; rehabilitation