title: Baclofen or nNOS inhibitor affect molecular and behavioral alterations evoked by traumatic spinal cord injury in rat spinal cord.
abstract: BACKGROUND
  The loss of descending control after spinal cord injury (SCI) and incessant stimulation of Ia monosynaptic pathway, carrying proprioceptive impulses from the muscles and tendons into the spinal cord, evoke exaggerated α-motoneuron activity leading to increased reflex response. Previous results from our laboratory have shown that Ia monosynaptic pathway is nitrergic.
  
  
  OBJECTIVE
  The aim of this study was to find out whether nitric oxide produced by neuronal nitric oxide synthase (nNOS) plays a role in setting the excitability of α-motoneurons after thoracic spinal cord transection.
  
  
  METHODS
  We tested the hypothesis that the inhibition of nNOS in α-motoneurons after SCI could have a neuroprotective effect on reflex response.
  
  
  METHODS
  Rats underwent spinal cord transection at Th10 level followed by 7, 10, and 14 days of survival. The animals were treated with Baclofen (a gamma aminobutyric acid B receptor agonist, 3 μg/two times per day/intrathecally) applied for 3 days from the seventh day after transection; N-nitro-l-arginine (NNLA) (nNOS blocator) applied for the first 3 days after injury (20 mg/kg per day, intramuscularly); NNLA and Baclofen; or NNLA (60 mg/kg/day, single dose) applied on the 10th day after transection. We detected the changes in the level of nNOS protein, nNOS messenger RNA, and nNOS immunoreactivity. To investigate the reflex response to heat-induced stimulus, tail-flick test was monitored in treated animals up to 16 days after SCI.
  
  
  RESULTS
  Our data indicate that Baclofen therapy is more effective than the combined treatment with NNLA and Baclofen therapy. The single dose of NNLA (60 mg/kg) applied on the 10th day after SCI or Baclofen therapy reduced nNOS expression in α-motoneurons and suppressed symptoms of increased reflex activity.
  
  
  CONCLUSIONS
  The results clearly show that increased nNOS expression in α-motoneurons after SCI may be pharmacologically modifiable with Baclofen or bolus dose of nNOS blocker.
authors.affiliation: Department of Neurodegeneration, Plasticity and Repair, Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, Košice 040 01, Slovakia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kisucká
authors.affiliation: Department of Neurodegeneration, Plasticity and Repair, Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, Košice 040 01, Slovakia.
authors.forename: Ľudmila
authors.initials: Ľ
authors.lastname: Hricová
authors.affiliation: Department of Neurodegeneration, Plasticity and Repair, Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, Košice 040 01, Slovakia.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pavel
authors.affiliation: Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland.
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Strosznajder
authors.affiliation: Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Chalimoniuk
authors.affiliation: Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland.
authors.forename: Jozef
authors.initials: J
authors.lastname: Langfort
authors.affiliation: Department of Neurodegeneration, Plasticity and Repair, Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, Košice 040 01, Slovakia.
authors.forename: Ján
authors.initials: J
authors.lastname: Gálik
authors.affiliation: Department of Neurodegeneration, Plasticity and Repair, Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, Košice 040 01, Slovakia; Anesthesiology Research Laboratory, University of California-San Diego, La Jolla, CA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Maršala
authors.affiliation: First Department of Surgery, University Hospital and Safarik University, SNP Street 1, Košice, Slovakia.
authors.forename: Jozef
authors.initials: J
authors.lastname: Radoňak
authors.affiliation: Department of Neurodegeneration, Plasticity and Repair, Institute of Neurobiology, Slovak Academy of Sciences, Šoltésovej 4, Košice 040 01, Slovakia. Electronic address: lukacova@saske.sk.
authors.forename: Nadežda
authors.initials: N
authors.lastname: Lukáčová
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D006358:Hot Temperature; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058748:Pain Perception / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D058786:GABA-B Receptor Agonists; D052248:Nitric Oxide Synthase Type I; D001418:Baclofen
keywords: Baclofen; NNLA; Neuronal nitric oxide synthase; Rat; Reflex response; Spinal cord injury; Tail-flick text; α-Motoneurons