Dataset Information

Bilateral contusion-compression model of incomplete traumatic cervical spinal cord injury.

ABSTRACT: Despite the increasing incidence and prevalence of cervical spinal cord injury (cSCI), we lack clinically relevant animal models that can be used to study the pathomechanisms of this injury and test new therapies. Here, we characterize a moderate cervical contusion-compression model in rats that is similar to incomplete traumatic cSCI in humans. We characterized the effects of 18-g clip-compression injury at cervical level C6 over an 8-week recovery period. Using Luxol fast blue/hematoxylin-eosin staining in combination with quantitative stereology, we determined that 18-g injury results in loss of gray matter (GM), white matter (WM), as well as in cavity formation. Magnetization transfer and T2-weighted magnetic resonance imaging were used to analyze lesion dynamics in vivo. This analysis demonstrated that both techniques are able to differentiate between the injury epicenter, subpial rim, and WM distal to the injury. Neurobehavioral assessment of locomotor function using Basso, Beattie, and Bresnahan (BBB) scoring and CatWalk revealed limited recovery from clip-compression injury at C6. Testing of forelimb function using grip strength demonstrated significant forelimb dysfunction, similar to the loss of upper-limb motor function observed in human cSCI. Sensory-evoked potentials recorded from the forelimb and Hoffman reflex recorded from the hindlimb confirmed the fore- and hindlimb deficits observed in our neurobehavioral analysis. Here, we have characterized a clip-compression model of incomplete cSCI that closely models this condition in humans. This work directly addresses the current lack of clinically relevant models of cSCI and will thus contribute to improved success in the translation of putative therapies into the clinic.

SUBMITTER: Forgione N

PROVIDER: S-EPMC4186801 | biostudies-other | 2014 Nov

REPOSITORIES: biostudies-other

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Bilateral contusion-compression model of incomplete traumatic cervical spinal cord injury.

Forgione Nicole N Karadimas Spyridon K SK Foltz Warren D WD Satkunendrarajah Kajana K Lip Alyssa A Fehlings Michael G MG

Journal of neurotrauma 20140912 21

Despite the increasing incidence and prevalence of cervical spinal cord injury (cSCI), we lack clinically relevant animal models that can be used to study the pathomechanisms of this injury and test new therapies. Here, we characterize a moderate cervical contusion-compression model in rats that is similar to incomplete traumatic cSCI in humans. We characterized the effects of 18-g clip-compression injury at cervical level C6 over an 8-week recovery period. Using Luxol fast blue/hematoxylin-eosi ...[more]

PMID: 24949719

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Project description:BackgroundGiven the indispensable role of animal models in preclinical studies of spinal cord injury (SCI) and the current state of available impactors, we designed a modified impactor for establishing contusion SCI in rats. The major improvement is the replacement of the impactor rod with a weight and an impactor tip.MethodsPreoperatively, radiographs of 8-week-old female Wistar rats were taken to establish a protocol for locating the target spinal segment. A total of 72 rats were randomly divided into 4 groups: the sham, 12.5-, 25- and 50-mm groups. Within 35 days postinjury (dpi), the Basso, Beattie, and Bresnahan locomotor rating scale (BBB) was used to evaluate the hindlimb motor function of the rats. At 7 dpi, the rats were sacrificed, and the spinal cord tissue was fixed. Hematoxylin-eosin (HE) staining was used to assess histological changes. Subsequently, immunofluorescence staining was performed to visualize the expression and distribution of GFAP, CD68, MBP, and NeuN. Additionally, rats were sacrificed, and their tissues were extracted for relevant protein assays. At 3 and 7 dpi, electrophysiological function was evaluated by measuring motor evoked potentials (MEPs) and sensory evoked potentials (SEPs).ResultsThe behavioral results revealed that higher strike heights were associated with lower BBB scores. Over time, the BBB scores of the SCI rats exhibited an improving trend. Quantitative analysis of the lesions indicated that as the impact height increased, the area of histological destruction, GFAP-negative area, CD68-positive cell count, and MBP-positive destruction area increased, and the number of NeuN-positive cells decreased. Western blot analysis further verified relevant protein changes. Electrophysiology confirmed that the MEP and SEP amplitudes decreased as the strike height increased.ConclusionsThus, these results confirm that this modified impactor can be used to establish a graded SCI model in rats. The model is clinically relevant, reproducible, stable, accessible, and affordable, providing a practical tool with which to elucidate the pathophysiological mechanisms and potential therapies for contusive SCI.

Dataset Information

Bilateral contusion-compression model of incomplete traumatic cervical spinal cord injury.

Publications

Bilateral contusion-compression model of incomplete traumatic cervical spinal cord injury.

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