Characterization of a cervical spinal cord hemicontusion injury in mice using the infinite horizon impactor.
The majority of clinical spinal cord injuries (SCIs) are contusive and occur at the cervical level of the spinal cord. Most scientists and clinicians agree that the preclinical evaluation of novel candidate treatments should include testing in a cervical SCI contusion model. Because mice are increasingly used because of the availability of genetically engineered lines, we characterized a novel cervical hemicontusion injury in mice using the Infinite Horizon Spinal Cord Impactor (Precisions Systems & Instrumentation, Lexington, KY). In the current study, C57BL/6 mice received a hemicontusion injury of 75 kilodynes with or without dwell time in an attempt to elicit a sustained moderate-to-severe motor deficit. Hemicontusion injuries without dwell time resulted in sustained deficits of the affected forepaw, as revealed by a 3-fold decrease in usage during rearing, a ∼50% reduction in grooming scores, and retrieval of significantly fewer pellets on the Montoya staircase test. Only minor transient deficits were observed in grasping force. CatWalk analysis revealed reduced paw-print size and swing speed of the affected forelimb. Added dwell time of 15 or 30 sec significantly worsened behavioral outcome, and mice demonstrated minimal ability of grasping, paw usage, and overground locomotion. Besides worsening of behavioral deficits, added dwell time also reduced residual white and gray matter at the epicenter and rostral-caudal to the injury, including on the contralateral side of the spinal cord. Taken together, we developed and characterized a new hemicontusion SCI model in mice that produces sufficient and sustained impairments in gross and skilled forelimb function and produced primarily unilateral functional deficits.
International Collaboration on Repair Discoveries-ICORD, Blusson Spinal Cord Center, Vancouver, British Columbia, Canada.
Femke
F
Streijger
Tim M J
TM
Beernink
Jae H T
JH
Lee
Tim
T
Bhatnagar
Soeyun
S
Park
Brian K
BK
Kwon
Wolfram
W
Tetzlaff
D000818:Animals; D002574:Cervical Vertebrae; D018737:Hand Strength / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019838:Neck Injuries / Q000503:physiopathology*; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*