Spinal cord injury – scientific challenges for the unknown future

Anderberg, Leif; Aldskogius, Håkan; Holtz, Anders

doi:10.3109/2000-1967-200

Cited by 36 publications

(24 citation statements)

References 66 publications

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“…Most SCI patients have injuries at the cervical level and the injuries are typically contusive [43, 50, 51]. We used a clinically relevant unilateral cervical contusion injury model in which spinal cords of adult rats were impacted at C5 level.…”

Section: Resultsmentioning

confidence: 99%

Local delivery of minocycline from metal ion-assisted self-assembled complexes promotes neuroprotection and functional recovery after spinal cord injury

et al. 2017

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Many mechanisms contribute to the secondary injury cascades following traumatic spinal cord injury (SCI). However, most current treatment strategies only target one or a few elements in the injury cascades, and have been largely unsuccessful in clinical trials. Minocycline hydrochloride (MH) is a clinically available antibiotic and anti-inflammatory drug that has been shown to target a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations. The inability to translate the high doses of MH used in experimental animals to tolerable doses in human patients limits its clinical efficacy. In addition, the duration of MH treatment is limited because long-term systemic administration of high doses of MH has been shown to cause liver toxicity and even death. We have developed a drug delivery system in the form of hydrogel loaded with polysaccharide-MH complexes self-assembled by metal ions for controlled release of MH. This drug delivery system can be injected into the intrathecal space for local delivery of MH with sufficient dose and duration, without causing any additional tissue damage. We show that local delivery of MH at a dose that is lower than the standard human dose (3 mg/kg) was more effective in reducing secondary injury and promoting locomotor functional recovery than systemic injection of MH with the highest dose and duration reported in experimental animal SCI (90–135 mg/kg).

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Section: Resultsmentioning

confidence: 99%

Local delivery of minocycline from metal ion-assisted self-assembled complexes promotes neuroprotection and functional recovery after spinal cord injury

et al. 2017

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“…These species have been used for combined electrophysiological and pharmacological studies of ion channel function and distribution in CNS myelinated axons (Kocsis, 1985;Eng et al, 1988;Fehlings and Nashmi, 1996;Nashmi et al, 2000;Sinha et al, 2006) and in studies of experimentally induced demyelination (Lo et al, 2003), traumatic (Fehlings and Nashmi, 1997;Nashmi et al, 2000;Nashmi and Fehlings, 2001a,b) or hypoxic/ischemic injury (Utzschneider et al, 1991;Imaizumi et al, 1998;Ouardouz et al, 2006) of axons, as well as to study the axonal properties in genetically modified animals with myelin abnormalities (Coetzee et al, 1996;Eftekharpour et al, 2005;Sinha et al, 2006) and to assess repair/remyelination of axonal tracts (McDonald and Howard, 2002;Anderberg et al, 2007;Eftekharpour et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Modular double sucrose gap apparatus for improved recording of compound action potentials from rat and mouse spinal cord white matter preparations

Velumian

Wan²,

Samoilova

et al. 2010

Journal of Neuroscience Methods

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“…8,10,13,17,27,30,31,35,40,49,51,65,68 Unlike with motor-complete SCI, hematomyelia is absent in those with motor-incomplete SCI. These patients have axonal swelling and disruption in conjunction with minimal coagulative necrosis of the spinal cord parenchyma.…”

mentioning

confidence: 99%

Predictors of intramedullary lesion expansion rate on MR images of patients with subaxial spinal cord injury

E¹,

Aarabi

Hersh³

et al. 2015

SPI

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OBJECT Studies of preclinical spinal cord injury (SCI) in rodents indicate that expansion of intramedullary lesions (IMLs) seen on MR images may be amenable to neuroprotection. In patients with subaxial SCI and motor-complete American Spinal Injury Association (ASIA) Impairment Scale (AIS) Grade A or B, IML expansion has been shown to be approximately 900 μm/hour. In this study, the authors investigated IML expansion in a cohort of patients with subaxial SCI and AIS Grade A, B, C, or D. METHODS Seventy-eight patients who had at least 2 MRI scans within 6 days of SCI were enrolled. Data were analyzed by regression analysis. RESULTS In this cohort, the mean age was 45.3 years (SD 18.3 years), 73 patients were injured in a motor vehicle crash, from a fall, or in sport activities, and 77% of them were men. The mean Injury Severity Score (ISS) was 26.7 (SD 16.7), and the AIS grade was A in 23 patients, B in 7, C in 7, and D in 41. The mechanism of injury was distraction in 26 patients, compression in 22, disc/osteophyte complex in 29, and Chance fracture in 1. The mean time between injury onset and the first MRI scan (Interval 1) was 10 hours (SD 8.7 hours), and the mean time to the second MRI scan (Interval 2) was 60 hours (SD 29.6 hours). The mean IML lengths of the first and second MR images were 38.8 mm (SD 20.4 mm) and 51 mm (SD 36.5 mm), respectively. The mean time from the first to the second MRI scan (Interval 3) was 49.9 hours (SD 28.4 hours), and the difference in IML lengths was 12.6 mm (SD 20.7 mm), reflecting an expansion rate of 366 μm/ hour (SD 710 μm/hour). IML expansion in patients with AIS Grades A and B was 918 μm/hour (SD 828 μm/hour), and for those with AIS Grades C and D, it was 21 μm/hour (SD 304 μm/hour). Univariate analysis indicated that AIS Grade A or B versus Grades C or D (p < 0.0001), traction (p= 0.0005), injury morphology (p < 0.005), the surgical approach (p= 0.009), vertebral artery injury (p= 0.02), age (p < 0.05), ISS (p < 0.05), ASIA motor score (p < 0.05), and time to decompression (p < 0.05) were all predictors of lesion expansion. In multiple regression analysis, however, the sole determinant of IML expansion was AIS grade (p < 0.005). CONCLUSIONS After traumatic subaxial cervical spine or spinal cord injury, patients with motor-complete injury (AIS Grade A or B) had a significantly higher rate of IML expansion than those with motor-incomplete injury (AIS Grade C or D).

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Spinal cord injury – scientific challenges for the unknown future

Abstract: The history of spinal cord injuries starts with the ancient

Cited by 36 publications

References 66 publications

Local delivery of minocycline from metal ion-assisted self-assembled complexes promotes neuroprotection and functional recovery after spinal cord injury

Local delivery of minocycline from metal ion-assisted self-assembled complexes promotes neuroprotection and functional recovery after spinal cord injury

Modular double sucrose gap apparatus for improved recording of compound action potentials from rat and mouse spinal cord white matter preparations

Predictors of intramedullary lesion expansion rate on MR images of patients with subaxial spinal cord injury

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