Cervical contusive trauma accounts for the majority, of human spinal cord injury (SCI), yet experimental use of cervical contusion injury models has been limited. Considering that (1) the different ways of injuring the spinal cord (compression, contusion, and transection) induce very different processes of tissue damage and (2) the architecture of the spinal cord is not uniform, it is important to use a model that is more clinically applicable to human SCI. Therefore, in the current study we have developed a rat model of contusive, cervical SCI using the Electromagnetic Spinal Cord Injury Device (ESCID) developed at Ohio State University (OSU) to induce injury by spinal cord displacement. We used the device to perform mild, moderate and severe injuries (0.80, 0.95, and 1.1 mm displacements, respectively) with a single, brief displacement of <20 msec upon the exposed dorsal surface of the C5 cervical spinal cord of female (180-200 g) Fischer rats. Characterization of the model involved the analysis of the temporal histopathological progression of the injury over 9 weeks using histochemical stains to analyze white and gray mater integrity and immunohistochemistry to examine cellular changes and physiological responses within the injured spinal cord. Accompanying the histological analysis was a comprehensive determination of the behavioral functionality of the animals using a battery of motor tests. Characterization of this novel model is presented to enable and encourage its future use in the design and experimental testing of therapeutic strategies that may be used for human SCI.

Schwann cell (SC) implantation alone has been shown to promote the growth of propriospinal and sensory axons, but not long-tract descending axons, after thoracic spinal cord injury (SCI). In the current study, we examined if an axotomy close to the cell body of origin (so as to enhance the intrinsic growth response) could permit supraspinal axons to grow onto SC grafts. Adult female Fischer rats received a severe (C5) cervical contusion (1.1 mm displacement, 3 KDyn). At 1 week postinjury, 2 million SCs ex vivo transduced with lentiviral vector encoding enhanced green fluorescent protein (EGFP) were implanted within media into the injury epicenter; injury-only animals served as controls. Animals were tested weekly using the BBB score for 7 weeks postimplantation and received at end point tests for upper body strength: self-supported forelimb hanging, forearm grip force, and the incline plane. Following behavioral assessment, animals were anterogradely traced bilaterally from the reticular formation using BDA-Texas Red. Stereological quantification revealed a twofold increase in the numbers of preserved NeuN+ neurons rostral and caudal to the injury/graft site in SC implanted animals, corroborating previous reports of their neuroprotective efficacy. Examination of labeled reticulospinal axon growth revealed that while rarely an axon was present within the lesion site of injury-only controls, numerous reticulospinal axons had penetrated the SC implant/lesion milieu. This has not been observed following implantation of SCs alone into the injured thoracic spinal cord. Significant behavioral improvements over injury-only controls in upper limb strength, including an enhanced grip strength (a 296% increase) and an increased self-supported forelimb hanging, accompanied SC-mediated neuroprotection and reticulospinal axon growth. The current study further supports the neuroprotective efficacy of SC implants after SCI and demonstrates that SCs alone are capable of supporting modest supraspinal axon growth when the site of axon injury is closer to the cell body of the axotomized neuron.Key words: Axon regeneration; Axotomy; Cell body response; Intrinsic; Neuron; Neuroprotection; Supraspinal INTRODUCTIONapies aimed at the promotion of axon growth (59,86,134,142), remyelination (17,22,64,71,73) or neuroreplacement (37,126,137,150). Among the most successful The spinal cord is a critical communication pathway for facilitating the bilateral transmission of sensory and strategies for SCI repair are those that involve exogenous cell implantation (105,106), often when combined motor modalities between the brain and the periphery. Injury to this structure often results in permanent paralywith additional pharmacological or molecular therapies (105,106). sis and lifelong disability (92). Treatments to target spinal cord injury (SCI) in experimental models have fo-The implantation of peripheral nerve grafts into the spinal cord was first used to demonstrate that, contrary cused on (i) protecting the spinal cord from secondary injury t...

A 43-year-old woman was su¤ering from an upper respiratory infection during the previous 7 days, followed by 3 days of severe headache. She was deeply drowsy 8 hours prior to admission. She had paranasal sinusitis (PNS) and had been for several years. Neurological examination revealed hyperreflexia. Analysis of the cerebrospinal fluid showed increased pressure, slightly turbid, 250 WBCs/cm 3 , 350 RBCs with a normal sugar level and protein of 540 mg/dl, oligoclonal band positive, and myelin sheath protein positive. The brain computed tomogram (CT) upon admission revealed a high-density thrombus in the vein of Galen and the straight sinus, and a marked bilateral hypodensity of the thalamus and the basal ganglia Fig. 1A). T2-weighted MRI revealed a high signal in the thalami, the basal ganglia, and the periventricular white matter Fig. 1B). The venous phase of carotid angiography demonstrated a lack of opacification of the deep cerebral veins, the inferior sagittal sinus, the vein of Galen, and the straight sinus Fig. 1C). Intravenous 1,500,000 IU of a bolus urokinase (UK) dosage was infused through the vein, and over the next 2 hours, 1,500,000 IU of UK was infused continuously. After UK infusion was finished, heparin was infused at 750 U per hour for the next two days. She was then given aspirin and coumadin. The patient awoke 2 days after treatment. A Follow-up CT, obtained 4 days later, demonstrated the resolution of the thalamic infarctions and straight sinus thrombus with a high density Fig. 1D). Cerebral angiography, obtained 3 weeks after the onset of the illness, disclosed recanalization of the deep cerebral vein Fig. 1E). The patient recovered dramatically.