Spinal cord injury, methylprednisolone

Koc RK, Akdemir H, Kurtsoy A, Pasaoglu H, Kavuncu I, Pasaoglu A, Karakucuk I. (1995). Lipid peroxidation in experimental spinal cord injury. Comparison of treatment with Ginkgo biloba, TRH, and methylprednisolone. Res Exp Med. 195(2) 117-123. 

Spinal cord injury IV Bolus 30 mg/kg over 15 min. Maintenance dose 5.4 mg/kg/hr over 23 hr, to be given within 45 min of bolus dose. IM (methylprednisolone acetate) 10-80 mg/day. Intra-artlcular, Intraleslonal 4-40 mg, up to 80 mg ql-5wk. 

There is also evidence that the neuroprotective properties of lipid-peroxidation-inhibiting doses of methylprednisolone, extensively studied in spinal-cord injury, are applicable to brain injury. The steroid has been shown to enhance the early recovery of mice subjected to a moderately severe concussive head injury when administered at 5 minutes post-injury [59], The dose-response curve for this effect is remarkably similar to that discussed above for spinal-cord injury. A 30mg/kg i.v. dose was observed to be optimal, while lower (15 mg/kg) and higher (60 and 120 mg/kg) doses were ineffective. 

High-dose methylprednisolone in spinal-cord injury... 

The results of the second National Acute Spinal Cord Injury Study (NASCIS II) constitutes a major milestone in the search for therapeutic interventions that will interfere significantly with secondary post-traumatic spinal-cord degeneration and thereby ameliorate the devastating neurological consequences of spinal-cord injury [64,65]. In that study, methylprednisolone was demonstrated to improve the 6- and 12-month recovery of spinal-cord injury patients, compared to placebo-treated patients, when administered in an intensive 24-hour intravenous antioxidant dosing regimen beginning within 8 hours after injury. NASCIS II is... 

Braughler, J.M., Hall, E.D., Means, E.D., Waters, T. and Anderson, D.K. (1987) Evaluation of an intensive methylprednisolone sodium succinate dosing regimen in experimental spinal cord injury, J. Neurosurg. 67, 102-105. 

Constantini S, Young W (1994) The effects of methylprednisolone and the ganghoside GMl on acute spinal cord injury in rats. J Neu-rosurg 80 97-111. 

Bracken MB, Shepard MJ, Hellenbrand KG, et al. Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study. J Neurosurg 1985 63(5) 704-713. 

In addition, glucocorticoids are used in spinal conditions. For example, methylprednisolone (32 mg/day) is used to reduce mortality in severe alcoholism and hepatitis and methylprednisolone (IV within 8 hours of injury) is used to improve neurogenic function in acute spinal cord injury (see also Table 14). 

Multicenter trials have shown significant decreases in neurological defects in patients with acute spinal cord injury treated within 8 hours of injury with large doses of methylprednisolone (30 mg/kg initially followed by an infusion of 5.4 mg/kg/h for 23 hours). 

Xiong Y, Rabchevsky AG, Hall ED (2007) Role of peroxynitrite in secondary oxidative damage after spinal cord injury. J Neurochem 100 639-649 Xu J, Fan GS, Chen SW, Wu YJ, Xu XM, Hsu CY (1998) Methylprednisolone inhibition of TNF-a expression and NF-cB activation after spintil cord injury in rats. Mol Biain Res 59 ... 

Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenbeig HM, Hamm E, Leo-Summers L, Maroon J (1990) A randomized, controUed trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the second national acute spinal cord injury study. N Engl J Med 322 1405-1411 Buki A, Parkas O, Doczi T, Povlishock JT (2003) Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumaticaUy induced axontil injury. J Neurotrauma 20 261-268 Bunge MB (2008) Novel combination strategies to repair the injured mammaUan spinal cord. J Spinal Cord Med 31 262-269... 

Chvatal SA, Kim YT, Bratt-Leal AM, Lee H, BeUamkonda RV (2008) Spatial distribution and acute anti-inflammatory effects of methylprednisolone after sustained local deUvety to the contused spinal cord. Biomaterials 29 1967-1975 Dasari VR, Spomar DG, Gondi CS, Sloffer CA, Saving KL, Gujrati M, Rao JS, Dinh DH (2007) Axonal remyelination by cord blood stem cells after spinal cord injury. J Neurotrauma 24 391 10... 

Kim YT, Caldwell JM, BeUamkonda RV (2009) Nanoparticle-mediated local dehvery of Methylprednisolone after spinal cord injury. Biomaterials 30 2582-2590... 

Wells JE, Rice TK, Nuttall RK, Edwards DR, ZekM H, Rivest S, Yong VW (2002) An adverse role for matrix metalloproteinase 12 after spinal cord injury in mice. J Neurosci 23 10107-10115 Xu J, Fan G, Chen S, Wu Y, Xu XM, Hsu CY (1998) Methylprednisolone inhibition of TNF-alpha expression and NF-kB activation after spinal cord injury in tats. Brain Res Mol Brain Res 59 135-142... 

In a related study on animals, it was reported that methylprednisolone sodium succinate as a treatment for acute spinal cord injury is a commonly used but controversial practice (19). Again in other studies on animals, it has been reported that it can be used as a neuroprotective agent as it decreases lipid peroxidation (20) that may contribute to free radical formation after acute spinal cord injury (21). In a study performed by O Kell ve Ambros (22) on animals, the authors were concerned that secondary to vasoconstriction, acute inflammation and ischemia could occur, and therefore, to minimize these potentially detrimental effects, methylprednisolone sodium succinate was administered. In our case, where dopamine was administered inadvertently through epidural catheter, no pathological findings were observed as a result of the examination performed as soon as the error was discovered and in the following 6-month clinical follow-up p>eriod. 

Subsequently, it was found that the substitution of a complex amine on the non-glucocorticoid steroid nucleus in place of the 21-hydroxyl functionality results in a dramatic enhancement of the lipid antioxidant activity. Many of these 21-aminosteroid compounds effectively inhibit iron-catalyzed lipid peroxidation in rat-brain tissue homogenates under assay conditions where the glucocorticoid steroid methylprednisolone and the non-glucocorticoid analog U-72099E are completely ineffective [20,21]. Of these, U-74006F (tirilazad mesylate Fig. 2) has shown excellent activity in experimental models of spinal-cord and brain injury. 

Hall, E.D. and Braughler, J.M. (1982) Effects of intravenous methylprednisolone on spinal cord lipid peroxidation and Na+ + K+-ATPase activity dose-response analysis during 1st hour after contusion injury in the cat. J. Neurosurg. 57, 247-253. 

Demopoulos, H.B., Flamm, E.S., Seligman, M.L., Pietronigro, D.D., Tomasula, J. and DeCrescito, V (1983) Further studies on free radical pathology in the major central nervous system disorders effects of very high doses of methylprednisolone on the functional outcome, morphology and chemistry of experimental spinal cord impact injury, Can. J. Physiol. 60, 1415— 1424. 

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