PMID- 19895872
OWN - NLM
STAT- MEDLINE
DCOM- 20100308
LR  - 20141120
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 165
IP  - 3
DP  - 2010 Feb 3
TI  - Neuroprotection of locomotor networks after experimental injury to the neonatal 
      rat spinal cord in vitro.
PG  - 996-1010
LID - 10.1016/j.neuroscience.2009.10.066 [doi]
AB  - Treatment to block the pathophysiological processes triggered by acute spinal 
      injury remains unsatisfactory as the underlying mechanisms are incompletely 
      understood. Using as a model the in vitro spinal cord of the neonatal rat, we 
      investigated the feasibility of neuroprotection of lumbar locomotor networks by 
      the glutamate antagonists 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) and 
      aminophosphonovalerate (APV) against acute lesions induced by either a toxic 
      solution (pathological medium (PM) to mimic the spinal injury 
      hypoxic-dysmetabolic perturbation) or excitotoxicity with kainate. The study 
      outcome was presence of fictive locomotion 24 h after the insult and its 
      correlation with network histology. Inhibition of fictive locomotion by PM was 
      contrasted by simultaneous and even delayed (1 h later) co-application of CNQX 
      and APV with increased survival of ventral horn premotoneurons and lateral column 
      white matter. Neither CNQX nor APV alone provided neuroprotection. 
      Kainate-mediated excitotoxicity always led to loss of fictive locomotion and 
      extensive neuronal damage. CNQX and APV co-applied with kainate protected 
      one-third of preparations with improved motoneuron and dorsal horn neuronal 
      counts, although they failed with delayed application. Our data suggest that 
      locomotor network neuroprotection was possible when introduced very early during 
      the pathological process of spinal injury, but also showed how the borderline 
      between presence or loss of locomotor activity was a very narrow one that 
      depended on the survival of a certain number of neurons or white matter elements. 
      The present report provides a model not only for preclinical testing of novel 
      neuroprotective agents, but also for estimating the minimal network membership 
      compatible with functional locomotor output.
CI  - Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Margaryan, G
AU  - Margaryan G
AD  - Neurobiology Sector, International School for Advanced Studies, 34151 Trieste, 
      Italy.
FAU - Mattioli, C
AU  - Mattioli C
FAU - Mladinic, M
AU  - Mladinic M
FAU - Nistri, A
AU  - Nistri A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091104
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Neuroprotective Agents)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/administration & dosage/*pharmacology
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/administration & dosage/*pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Survival/drug effects
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Efferent Pathways/drug effects/physiopathology
MH  - Excitatory Amino Acid Antagonists/administration & dosage/pharmacology
MH  - In Vitro Techniques
MH  - Kainic Acid
MH  - Locomotion/*drug effects/physiology
MH  - Motor Neurons/drug effects/physiology
MH  - Nerve Fibers, Myelinated/drug effects/physiology
MH  - Neurons/drug effects/physiology
MH  - Neuroprotective Agents/administration & dosage/*pharmacology
MH  - Posterior Horn Cells/drug effects/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Spinal Cord Injuries/chemically induced/*drug therapy/physiopathology
MH  - Time Factors
EDAT- 2009/11/10 06:00
MHDA- 2010/03/10 06:00
CRDT- 2009/11/10 06:00
PHST- 2009/08/03 00:00 [received]
PHST- 2009/10/07 00:00 [revised]
PHST- 2009/10/29 00:00 [accepted]
PHST- 2009/11/10 06:00 [entrez]
PHST- 2009/11/10 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
AID - S0306-4522(09)01793-X [pii]
AID - 10.1016/j.neuroscience.2009.10.066 [doi]
PST - ppublish
SO  - Neuroscience. 2010 Feb 3;165(3):996-1010. doi: 
      10.1016/j.neuroscience.2009.10.066. Epub 2009 Nov 4.