Cervical Hemicontusion Research Articles

Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats

The majority of spinal cord injuries (SCIs) in the clinic occur at the lower cervical levels, resulting in both white and gray matter disruption. In contrast, most experimental models of SCI in rodents induce damage in the thoracic cord, resulting primarily in white matter disruption. To address this disparity, experimental cervical SCI models have been developed. Thus, we used a recently characterized model of cervical hemicontusion SCI in adult male rats to assess the potential therapeutic effect of post-SCI administration of 17β-estradiol. Rats received a hemicontusion at the level of the fifth cervical vertebra (C5) followed by administration of 17β-estradiol via a slow release pellet (0.5 or 5.0 mg/pellet) beginning at 30 minutes post-SCI. Behavioral evaluation of skilled and unskilled forelimb function and locomotor function were conducted for 7 weeks after SCI. Upon conclusion of the behavioral assessments, spinal cords were collected and histochemistry and stereology were conducted to evaluate the effect of treatment on the lesion characteristics. We found that post-SCI administration of 17β-estradiol decreased neuronal loss in the ventral horn, decreased reactive astrogliosis, decreased the immune response, and increased white mater sparing at the lesion epicenter. Additionally, post-SCI administration of 17β-estradiol improved skilled forelimb function and locomotor function. Taken together, these data suggest that post-SCI administration of 17β-estradiol protected both the gray and white matter in cervical SCI. Moreover, this treatment improved function on skilled motor tasks that involve both gray and white matter components, suggesting that this is likely a highly clinically relevant protective strategy.

Magnesium in a Polyethylene Glycol Formulation Provides Neuroprotection After Unilateral Cervical Spinal Cord Injury

Experimental animal study. To investigate the neuroprotective efficacy of this magnesium in polyethylene glycol (PEG) formulation in a contusive model of cervical spinal cord injury (SCI). Intravenously administered magnesium has been extensively investigated as a neuroprotective agent in animal models of SCI, stroke, and traumatic brain injuries, and has been evaluated in large scale clinical trials for the latter 2 indications. We have developed a novel formulation of magnesium chloride (MgCl₂) within PEG, and have previously demonstrated the neuroprotective benefit of this formulation in animal models of thoracic SCI. Twenty-two Sprague Dawley rats underwent a unilateral cervical hemicontusion at C4-C5 and were randomized 2 hours later to either the MgCl₂ in PEG formulation, or normal saline. Each treatment was administered in 5 intravenous infusions spaced 6 hours apart. Behavioral recovery was assessed over 6 weeks, after which the cord was analyzed to measure the extent of gray matter and white matter sparing through the injury site. In the horizontal ladder test, the percentage of forelimb errors made by the animals treated with MgCl₂ in PEG formulation was significantly lower than the saline-treated controls. Histologic analysis also revealed a significantly higher cumulative white matter sparing through the injury site in the MgCl₂ in PEG group. MgCl₂ in a PEG formulation reduced secondary damage and improved behavioral recovery when administered 2 hours after a unilateral cervical hemicontusion injury. These findings are consistent with the neurologic benefit observed when administering this magnesium formulation in contusive and compressive models of thoracic SCI. Demonstrating the robustness of this neuroprotective effect in multiple injury models (and in the cervical injury model in particular) is important when considering the applicability of such a therapy for human SCIs.

Characterization of a Graded Cervical Hemicontusion Spinal Cord Injury Model in Adult Male Rats

Most experimental models of spinal cord injury (SCI) in rodents induce damage in the thoracic cord and subsequently examine hindlimb function as an indicator of recovery. In these models, functional recovery is most attributable to white-matter preservation and is less influenced by grey-matter sparing. In contrast, most clinical cases of SCI occur at the lower cervical levels, a region in which both grey-matter and white-matter sparing contribute to functional motor recovery. Thus experimental cervical SCI models are beginning to be developed and used to assess protective and pharmacological interventions following SCI. The objective of this study was to characterize a model of graded cervical hemicontusion SCI with regard to several histological and behavioral outcome measures, including novel forelimb behavioral tasks. Using a commercially available rodent spinal cord impactor, adult male rats received hemicontusion SCI at vertebral level C5 at 100, 200, or 300 kdyn force, to produce mild, moderate, or severe injury severities. Tests of skilled and unskilled forelimb and locomotor function were employed to assess functional recovery, and spinal cord tissue was collected to assess lesion severity. Deficits in skilled and unskilled forelimb function and locomotion relating to injury severity were observed, as well as decreases in neuronal numbers, white-matter area, and white-matter gliosis. Significant correlations were observed between behavioral and histological data. Taken together, these data suggest that the forelimb functional and locomotor assessments employed here are sensitive enough to measure functional changes, and that this hemicontusion model can be used to evaluate potential protective and regenerative therapeutic strategies.

17β‐Estradiol protects Schwann cells against H2O2‐induced cytotoxicity and increases transplanted Schwann cell survival in a cervical hemicontusion spinal cord injury model

Schwann cell (SC) transplantation is a promising repair strategy after spinal cord injury (SCI); however, a large number of SCs do not survive following transplantation. Previous studies have shown that 17β-estradiol (E2) protects several cell types against cytotoxicity. Thus, this study evaluated the protective potential of E2 on SCs in vitro and investigated the effect of E2 on transplanted SC survival in a rat model of SCI. Primary SC cultures were found to robustly express estrogen receptors (ER) and incubation with E2 protected SCs against hydrogen peroxide-induced cell death. This protection was not inhibited by the ER antagonist ICI 182,780, suggesting that genomic signaling is not necessary for protection. In a subsequent experiment, cervical hemicontusion SCI was induced in male rats followed by sustained administration of E2 or placebo. Eight days after SCI, SCs were transplanted into the injury epicenter. E2 treatment significantly increased the number of surviving labeled transplanted SCs evaluated 7 days after transplantation. These data demonstrate that E2 protects SCs against oxidative stress and improves transplanted SC survival, which suggests that E2 administration may be an intervention of choice for enhancing survival of transplanted SCs after SCI.

Comment: modeling for drug development in spinal cord injury.

Journal of NeurotraumaVol. 9, No. 2 Comment: Modeling for Drug Development in Spinal Cord InjuryDENNIS W. CHOIDENNIS W. CHOISearch for more papers by this authorPublished Online:26 Mar 2009https://doi.org/10.1089/neu.1992.9.135AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byMolecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair17 May 2012 | Cell and Tissue Research, Vol. 349, No. 1Characterization of a Graded Cervical Hemicontusion Spinal Cord Injury Model in Adult Male Rats Kelly A. Dunham, Akkradate Siriphorn, Supin Chompoopong, and Candace L. Floyd18 November 2010 | Journal of Neurotrauma, Vol. 27, No. 11Effects of Methylprednisolone on the Neural Conduction of the Motor Evoked Potentials in Spinal Cord Injured RatsJournal of Korean Medical Science, Vol. 20, No. 1Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury23 February 2004 | Proceedings of the National Academy of Sciences, Vol. 101, No. 9Morphological Characterization of Photochemical Graded Spinal Cord Injury in the Rat Enrique Verdú, Guillermo García-Alías, Joaquim Forés, José M. Vela, Jordi Cuadras, Ruben López-Vales, and Xavier Navarro8 July 2004 | Journal of Neurotrauma, Vol. 20, No. 5Animal Models Used in Spinal Cord Regeneration ResearchSpine, Vol. 27, No. 14Graded Contusion Model of the Mouse Spinal Cord Using a Pneumatic Impact DeviceNeurosurgery, Vol. 50, No. 5Effects of dexamethasone on apoptosis-related cell death after spinal cord injuryJournal of Neurosurgery: Spine, Vol. 96, No. 1Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injuryJournal of Neurosurgery: Spine, Vol. 94, No. 2Perfusion-Limited Recovery of Evoked Potential Function After Spinal Cord InjurySpine, Vol. 25, No. 10Traumatic Spinal Cord Injury Produced by Controlled Contusion in MouseJournal of Neurotrauma, Vol. 17, No. 4Effect of Treatment With 21-Aminosteroid U-74389G and Glucocorticoid Steroid Methylprednisolone on Somatosensory Evoked Potentials in Rat Spinal Cord During Mild CompressionJournal of Neurotrauma, Vol. 16, No. 2In Vivo Bcl-2 Oncogene Neuronal Expression in the Rat Spinal CordSpine, Vol. 23, No. 5Early Time-Dependent Decompression for Spinal Cord Injury: Vascular Mechanisms of RecoveryJournal of Neurotrauma, Vol. 14, No. 12Viscoelastic Relaxation and Regional Blood Flow Response to Spinal Cord Compression and DecompressionSpine, Vol. 22, No. 12 Volume 9Issue 2Jan 1992 To cite this article:DENNIS W. CHOI.Comment: Modeling for Drug Development in Spinal Cord Injury.Journal of Neurotrauma.Jan 1992.135-137.http://doi.org/10.1089/neu.1992.9.135Published in Volume: 9 Issue 2: March 26, 2009PDF download