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ABSTRACT: 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.
Spine 10/2010; 35(23):2041-8. · 2.08 Impact Factor
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ABSTRACT: A number of drugs commonly used for a variety of clinical indications have been found recently to have substantial neuroprotective properties, raising the potential for rapid translation into human clinical trials of spinal cord injury (SCI). In this study we compared the neuroprotective efficacy of erythropoietin and a derivative of it, darbepoetin, in an acute model of thoracic SCI. Sprague-Dawley rats were randomized to receive erythropoietin (5000 IU/kg), darbepoetin (10 mug/kg), or saline, as a single intravenous injection 1 h after a thoracic contusion SCI. The animals were evaluated for behavioral recovery over 6 weeks, which included BBB locomotor testing, horizontal ladder testing, video-analysis of gait, and hindlimb monofilament sensory testing. At 6 week post-injury, the spinal cords were evaluated histologically to measure white and grey matter sparing at and around the epicenter of injury. We found that neither erythropoietin nor darbepoetin led to improved behavioral recovery over saline controls, with no significant differences observed in BBB scores, BBB subscores, footfall errors on horizontal ladder testing, width of hindlimb base of support, or threshold for paw withdrawal on sensory testing. Furthermore, no differences were observed in grey or white matter sparing between the three experimental groups. Using doses of erythropoietin and darbepoetin that other investigators have reported to be beneficial in SCI and stroke models, we were unable to demonstrate a neuroprotective effect when administered 1 h after injury. Further preclinical investigation is necessary to refine the treatment strategy of using erythropoietin or darbepoetin in acute spinal cord injury.
Experimental Neurology 06/2008; 211(1):34-40. · 4.70 Impact Factor
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ABSTRACT: Interest in systemic and local hypothermia extends back over many decades, and both have been investigated as potential neuroprotective interventions in a number of clinical settings, including traumatic brain injury, stroke, cardiac arrest, and both intracranial and thoracoabdominal aortic aneurysm surgery. The recent use of systemic hypothermia in an injured National Football League football player has focused a great deal of attention on the potential use of hypothermia in acute spinal cord injury.
To provide spinal clinicians with an overview of the biological rationale for using hypothermia, the past studies and current clinical applications of hypothermia, and the basic science studies and clinical reports of the use of hypothermia in acute traumatic spinal cord injury.
A review of the English literature on hypothermia was performed, starting with the original clinical description of the use of systemic hypothermia in 1940. Pertinent basic science and clinical articles were identified using PubMed and the bibliographies of the articles.
Each article was reviewed to provide a concise description of hypothermia's biological rationale, current clinical applications, complications, and experience as a neuroprotective intervention in spinal cord injury.
Hypothermia has a multitude of physiologic effects. From a neuroprotective standpoint, hypothermia slows basic enzymatic activity, reduces the cell's energy requirements, and thus maintains Adenosine Triphosphate (ATP) concentrations. As such, systemic hypothermia has been shown to be neuroprotective in patients after cardiac arrest, although its benefit in other clinical settings such as traumatic brain injury, stroke, and intracranial aneurysm surgery has not been demonstrated. Animal studies of local and systemic hypothermia in traumatic spinal cord injury models have produced mixed results. Local hypothermia was actively studied in the 1970s in human acute traumatic spinal cord injury, but no case series of this intervention has been published since 1984. No peer-reviewed clinical literature could be found, which describes the application of systemic hypothermia in acute traumatic spinal cord injury.
Animal studies of acute traumatic spinal cord injury have not revealed a consistent neuroprotective benefit to either systemic or local hypothermia. Human studies of local hypothermia after acute traumatic spinal cord injury have not been published for over two decades. No peer-reviewed studies describing the use of systemic hypothermia in this setting could be found. Although a cogent biological rationale may exist for the use of local or systemic hypothermia in acute traumatic spinal cord injury, there is little scientific literature currently available to substantiate the clinical use of either in human patients.
The Spine Journal 04/2008; 8(6):859-74. · 3.29 Impact Factor
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ABSTRACT: A retrospective study was conducted.
To determine the exact distal fusion level in the treatment of single thoracic idiopathic scoliosis (King Types 3 and 4) with segmental pedicle screw fixation.
Pedicle screw fixation effectively shortens the distal fusion extent by improved three-dimensional deformity correction. However, the selection of distal fusion extent remains controversial in single thoracic idiopathic scoliosis.
This study analyzed 42 patients with single thoracic adolescent idiopathic scoliosis (32 King 3 patients and 10 King 4 patients) who underwent segmental pedicle screw fixation and had a minimum follow-up period of 2 years (range, 2-6 years). The patients were grouped according to the distal fusion level with reference to the standing neutral rotated vertebra (NV) for comparison of deformity correction and spinal balance using standing radiographs. Failure to restore an adequate trunk balance and progression or extension of the primary curve (adding on) was considered unsatisfactory.
Preoperative 50 degrees +/- 11 degrees of thoracic deformity was corrected to 13 degrees +/- 5 degrees, for a curve correction of 74%. Preoperative 23 degrees +/- 7 degrees of lumbar deformity was corrected to 2 degrees +/- 8 degrees, for a curve correction of 93%. Curve correction was not significantly affected by King type or distal fusion level (P > 0.05). Postoperative unsatisfactory results were obtained in 14 patients. When the preoperative NV was the same or one level distal to end vertebra (EV), fusion down to NV was satisfactory (14/14). When the preoperative NV was more than two levels distal to EV, fusion down to one level shorter than NV (NV-1) also was satisfactory (9/9). However, when fusion down to NV-2 or shorter was performed, the chances of adding on were higher (14/19; P < 0.01). Preoperative 17 degrees +/- 8 degrees of thoracic kyphosis was improved to 24 degrees +/- 7 degrees.
In single thoracic idiopathic scoliosis, NV is an important factor for the determination of fusion level. When preoperative NV and EV show no more than two-level gap differences, the curve should be fused down to NV. When the gap is more than two levels, fusion down to NV-1 is satisfactory, saving one or two motion segments, as compared with fusion extending to the stable vertebra.
Spine 03/2003; 28(5):484-91. · 2.08 Impact Factor
