A remotely controlled model of spinal cord compression injury in mice: toward real-time analysis.
OBJECTIVE
To date, there has been no efficient therapeutic approach to spinal cord injuries (SCIs). This may be attributable, at least in part, to difficulties in forming predictive and accurate experimental animal models. The authors' previous studies have identified 2 relevant conditions of such a model. The first condition is the ability to compare data derived from rat models of SCI by developing mouse models of SCI that permit access to a large range of transgenic models. The second condition is that the exploration of the consequences of each mechanism of spinal trauma requires modeling the different etiologic aspects of the injury.


METHODS
To fulfill these 2 conditions a new model of mouse spinal cord compression injury was devised using a thread-driven olive-shaped compressive device. The authors characterized early motor, sensory, and histological outcomes using 3 olive diameters and different compression durations.


RESULTS
A gradual and reproducible functional severity that correlated with lesion extension was demonstrated in 76 mice. To further substantiate the characterization of this model, a noncompetitive N-methyl-d-aspartate antagonist was administered in 30 mice, which demonstrated the involvement of excitotoxicity in this model.


CONCLUSIONS
The study demonstrated that spinal olive-compression injury in the mouse is a reproducible, well-characterized, and predictable model for analyzing early events after SCI. The nonmagnetic and remotely controlled design of this model will allow completion of the lesion while the animal is in the MR imaging apparatus, thus permitting further real-time MR imaging studies that will provide insights into the characterization of early events in the spatial and temporal evolution of SCI. Moreover, this model lays the foundation for future in vivo studies of functional and histological outcomes following SCI in genetically engineered animals.
Kouyoumdjian
Pascal
P
Pathophysiology and Therapy of Sensory and Motor Deficits, Institute for Neurosciences of Montpellier, INSERM U583, Saint Eloi Hospital, Montpellier, France.
Lonjon
Nicolas
N
Prieto
Monica
M
Haton
Henri
H
Privat
Alain
A
Asencio
Gérard
G
Perrin
Florence E
FE
Gaviria
Manuel
M
D000818:Animals; D001522:Behavior, Animal; D053138:Cyclohexenes / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D018696:Neuroprotective Agents / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D020127:Recovery of Function; D013117:Spinal Cord Compression / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors
D053138:Cyclohexenes; D018696:Neuroprotective Agents; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C070707:gacyclidine