PMID- 22708918
OWN - NLM
STAT- MEDLINE
DCOM- 20121227
LR  - 20211021
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 29
IP  - 12
DP  - 2012 Aug 10
TI  - Acute molecular perturbation of inducible nitric oxide synthase with an antisense 
      approach enhances neuronal preservation and functional recovery after contusive 
      spinal cord injury.
PG  - 2244-9
LID - 10.1089/neu.2012.2371 [doi]
AB  - Inducible nitric oxide synthase (iNOS) is a key mediator of inflammation and 
      oxidative stress produced during pathological conditions, including 
      neurodegenerative diseases and central nervous system (CNS) injury. iNOS is 
      responsible for the formation of high levels of nitric oxide (NO). The production 
      of highly reactive and cytotoxic NO species, such as peroxynitrite, plays an 
      important role in secondary tissue damage. We have previously demonstrated that 
      acute administration of iNOS antisense oligonucleotides (ASOs) 3 h after moderate 
      contusive spinal cord injury (SCI) potently inhibits iNOS-mediated increases in 
      NO levels, leading to reduced blood-spinal cord barrier permeability, decreased 
      neutrophil accumulation, and less neuronal cell death. In the current study we 
      investigated if iNOS ASOs could also provide long-term (10-week) histological and 
      behavioral improvements after moderate thoracic T8 contusive SCI. Adult rats were 
      randomly assigned to three groups (n=10/group): SCI alone, SCI and mixed base 
      control oligonucleotides (MBOs), or SCI and iNOS ASOs (200 nM). Oligonucleotides 
      were administered by spinal superfusion 3 h after injury. Behavioral analysis 
      (Basso-Beattie-Bresnahan [BBB] score and subscore) was employed weekly for 10 
      weeks post-SCI. Although animals treated with iNOS ASOs demonstrated no 
      significant differences in BBB scores compared to controls, subscore analysis 
      revealed a significant improvement in foot positioning, trunk stability, and tail 
      clearance. Histologically, while no gross improvement in preserved white and gray 
      matter was observed, greater numbers of surviving neurons were present adjacent 
      to the lesion site in iNOS ASO-treated animals than controls. These results 
      support the effectiveness of targeting iNOS acutely as a therapeutic approach 
      after SCI.
FAU - Maggio, Dominic M
AU  - Maggio DM
AD  - The Miami Project to Cure Paralysis, The Neuroscience Program, The 
      Interdisciplinary Stem Cell Institute, University of Miami, Miller School of 
      Medicine, Miami, Florida, USA.
FAU - Chatzipanteli, Katina
AU  - Chatzipanteli K
FAU - Masters, Neil
AU  - Masters N
FAU - Patel, Samik P
AU  - Patel SP
FAU - Dietrich, W Dalton
AU  - Dietrich WD
FAU - Pearse, Damien D
AU  - Pearse DD
LA  - eng
GR  - P01 NS38665/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Amidines)
RN  - 0 (Benzylamines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Guanidines)
RN  - 0 (N-(3-(aminomethyl)benzyl)acetamidine)
RN  - 0 (Oligonucleotides, Antisense)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - SCQ4EZQ113 (pimagedine)
SB  - IM
MH  - Amidines/pharmacology/therapeutic use
MH  - Animals
MH  - Benzylamines/pharmacology/therapeutic use
MH  - Blood-Brain Barrier
MH  - Contusions/enzymology/therapy
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Guanidines/pharmacology/therapeutic use
MH  - Locomotion/physiology
MH  - Neurons/*enzymology
MH  - Nitric Oxide Synthase Type II/*antagonists & inhibitors/*genetics
MH  - Oligonucleotides, Antisense/*pharmacology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Recovery of Function/*genetics
MH  - Spinal Cord Injuries/*enzymology/*therapy
PMC - PMC3419843
EDAT- 2012/06/20 06:00
MHDA- 2012/12/28 06:00
PMCR- 2013/08/10
CRDT- 2012/06/20 06:00
PHST- 2012/06/20 06:00 [entrez]
PHST- 2012/06/20 06:00 [pubmed]
PHST- 2012/12/28 06:00 [medline]
PHST- 2013/08/10 00:00 [pmc-release]
AID - 10.1089/neu.2012.2371 [pii]
AID - 10.1089/neu.2012.2371 [doi]
PST - ppublish
SO  - J Neurotrauma. 2012 Aug 10;29(12):2244-9. doi: 10.1089/neu.2012.2371.