Characterization of a Cervical Spinal Cord Hemicontusion Injury in Mice Using the Infinite Horizon Impactor Femke Streijger 1 Tim M.J. Beernink 1 Jae H.T Lee 1 Tim Bhatnagar 1,2 Soeyun Park, 1,3 Brian K. Kwon, 1,3,4 and Wolfram Tetzlaff 1,3 Abstract 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. Key words: cervical hemicontusion; compression; dwell time; forelimb function; spinal cord injury Introduction W ith an average of 10,000 people a year in North America and an annual total cost of approximately USD$4 billion, spinal cord injury (SCI) is considered to be the most ex- pensive chronic medical condition with few established treatments available. 1 Close to two thirds of all reported human SCIs are partial lesions, with the majority occurring in the cervical spinal cord. 1 Limited functioning of both upper limbs severely affects the ability to carry out activities of daily living, ranging from self-care to basic work activities, critical for independent living. Given that regaining arm and hand function is a top priority for the majority of tetraplegic individuals, 2 there is a compelling rationale for evalu- ating therapies in cervical injury models, where recovery of fore- limb function can be used as an outcome measure. During the past decade, there has been intensive research into molecular and cellular factors determining neurological recovery after SCI in the hope of finding an effective therapeutic strategy. 3–6 Genetically engineered mouse models that permit (conditional) expression or inactivation of genes have served as valuable in vivo tools to test molecular pathomechanisms and provide proof of principle for promising therapeutics. 7–10 Though many SCI studies in mice have been performed at the thoracic level, few have in- volved cervical lesions of the spinal cord. 11–15 It is noteworthy that findings in thoracic injury models may not be directly applicable to injuries at the cervical level. Thoracic SCIs produce behavioral deficits by damaging long axons of ascending and descending tracts in the white matter. Little functional abnormalities observed can be attributed to loss of gray matter, such as interneurons and/or motor neurons at the level of injury. A number of models of traumatic or atraumatic cervical SCI have been previously reported on, in which the spinal cord is in- jured by contusion, dislocation, distraction, compression, crush, sharp transection, excitatory neurotoxins, or irradiation injuries. 16–28 1 International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Center, Vancouver, British Columbia, Canada. 2 Department of Mechanical Engineering, Faculty of Applied Science, University of British Columbia, Vancouver, British Columbia, Canada. 3 Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada. 4 Combined Neurosurgical and Orthopedic Spine Program (CNOSP), Department of Orthopedics, University of British Columbia, Vancouver, British Columbia, Canada. JOURNAL OF NEUROTRAUMA 30:869–883 (May 15, 2013) ª Mary Ann Liebert, Inc. DOI: 10.1089/neu.2012.2405 869