PMID- 24508749
OWN - NLM
STAT- MEDLINE
DCOM- 20141209
LR  - 20220321
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 265
DP  - 2014 Apr 18
TI  - Riluzole improves outcome following ischemia-reperfusion injury to the spinal 
      cord by preventing delayed paraplegia.
PG  - 302-12
LID - S0306-4522(14)00080-3 [pii]
LID - 10.1016/j.neuroscience.2014.01.059 [doi]
AB  - The spinal cord is vulnerable to ischemic injury due to trauma, vascular 
      malformations and correction of thoracic aortic lesions. Riluzole, a sodium 
      channel blocker and anti-glutamate drug has been shown to be neuroprotective in a 
      model of ischemic spinal cord injury, although the effects in clinically relevant 
      ischemia/reperfusion models are unknown. Here, we examine the effect of riluzole 
      following ischemia-reperfusion injury to the spinal cord. Female rats underwent 
      high thoracic aortic balloon occlusion to produce an ischemia/reperfusion injury. 
      Tolerance to ischemia was evaluated by varying the duration of occlusion. 
      Riluzole (8mg/kg) was injected intraperitoneally 4h after injury. Locomotor 
      function (Basso, Beattie and Bresnahan (BBB) scale) was assessed at 4h, 1day, and 
      5days post-ischemia. Spinal cords were extracted and evaluated for neuronal loss 
      using immunohistology (choline acetyltransferase (ChAT) and neuronal nuclei 
      (NeuN)), inflammation (CD11b), astrogliosis (glial fibrillary acidic protein - 
      GFAP) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling 
      (TUNEL). Ischemic injury lasting between 5.5 and 6.75min resulted in delayed 
      paraplegia, whereas longer ischemia induced immediate paraplegia. When riluzole 
      was administered to rats that underwent 6min of occlusion, delayed paraplegia was 
      prevented. The BBB score of riluzole-treated rats was 11.14+/-4.85 compared with 
      1.86+/-1.07 in control animals. Riluzole also reduced neuronal loss, infiltration 
      of microglia/macrophages and astrogliosis in the ventral horn and intermediate 
      zone of the gray matter. In addition, riluzole reduced apoptosis of neurons in 
      the dorsal horn of the gray matter. Riluzole has a neuroprotective effect in a 
      rat model of spinal cord injury/reperfusion when administered up to 4h 
      post-injury, a clinically relevant therapeutic time window.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Wu, Y
AU  - Wu Y
AD  - Toronto Western Research Institute and Krembil Neuroscience Centre, University 
      Health Network, University of Toronto, Canada.
FAU - Satkunendrarajah, K
AU  - Satkunendrarajah K
AD  - Toronto Western Research Institute and Krembil Neuroscience Centre, University 
      Health Network, University of Toronto, Canada.
FAU - Fehlings, M G
AU  - Fehlings MG
AD  - Toronto Western Research Institute and Krembil Neuroscience Centre, University 
      Health Network, University of Toronto, Canada; Division of Neurosurgery, 
      University Health Network, University of Toronto, Canada. Electronic address: 
      michael.fehlings@uhn.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140206
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Neuroprotective Agents)
RN  - 7LJ087RS6F (Riluzole)
SB  - IM
MH  - Animals
MH  - Female
MH  - Neuroprotective Agents/*therapeutic use
MH  - Paraplegia/etiology/*prevention & control
MH  - Rats
MH  - Reperfusion Injury/*drug therapy
MH  - Riluzole/*therapeutic use
MH  - Spinal Cord Injuries/complications/*drug therapy/pathology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - drug treatment
OT  - ischemia
OT  - ischemia-reperfusion injury
OT  - riluzole
OT  - spinal cord injury
EDAT- 2014/02/11 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/02/11 06:00
PHST- 2013/10/23 00:00 [received]
PHST- 2014/01/17 00:00 [revised]
PHST- 2014/01/28 00:00 [accepted]
PHST- 2014/02/11 06:00 [entrez]
PHST- 2014/02/11 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0306-4522(14)00080-3 [pii]
AID - 10.1016/j.neuroscience.2014.01.059 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Apr 18;265:302-12. doi: 10.1016/j.neuroscience.2014.01.059. 
      Epub 2014 Feb 6.