Abstract
Study design:
Experimental animal study.
Objectives:
Quantitative analysis of secondary changes in lesion size after experimental spinal cord injury (SCI) in the rat, with special emphasis to the formation of dorsal column lesions.
Setting:
Slovakia.
Methods:
After SCI in the rat, animals survived for different periods ranging from 5 min to 7 days. Their whole spinal cords were cut transversally into 1 mm thick slabs. On each slab, the lesion profile was outlined. The overall shape of the lesion was reconstructed from a series of consecutive profiles and its length was measured.
Results:
Immediately after injury, a spindle-shaped hemorrhagic contusive lesion was observed, with the length of ~15 mm. After a quiescent phase lasting for at least 1 h, there was a dramatic secondary enlargement of the lesion and its length increased up to 40 mm between 1 and 48 h. The fully developed lesion consisted of the spindle-shaped epicenter and long cranial and caudal protrusions located in the midline between dorsal columns.
Conclusion:
We propose that secondary enlargement of the lesion can be explained by posttraumatic swelling. The expanding tissues are pushed out in longitudinal axis along the mechanically weakest parts of the spinal cord. Additional data that support this hypothesis are presented. Our findings indicate that malignant posttraumatic edema might have an important role in pathomechanisms of secondary injury after SCI.
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References
Vanicky I, Urdzikova L, Saganova K, Cizkova D, Galik J . A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat. J Neurotrauma 2001; 18: 1399–1407.
Vanicky I, Ondrejcak T, Ondrejcakova M, Sulla I, Galik J . Long-term changes in spinal cord evoked potentials after compression spinal cord injury in the rat. Cell Mol Neurobiol 2006; 26: 1521–1539.
Vanický I, Urdzíková L, Saganová K, Maršala M . Intrathecal methylprednisolone does not improve outcome after severe spinal cord injury in the rat. Neurosci Res Commun 2002; 31: 183–191.
Saganova K, Orendacova J, Cizkova D, Vanicky I . Limited minocycline neuroprotection after balloon-compression spinal cord injury in the rat. Neurosci Lett 2008; 433: 246–249.
Saganova K, Orendacova J, Sulla I Jr, Filipcik P, Cizkova D, Vanicky I . Effects of long-term FK506 administration on functional and histopathological outcome after spinal cord injury in adult rat. Cell Mol Neurobiol 2009; 29: 1045–1051.
Balentine JD . Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest 1978; 39: 236–253.
Guth L, Zhang Z, Steward O . The unique histopathological responses of the injured spinal cord. Implications for neuroprotective therapy. Ann NY Acad Sci 1999; 890: 366–384.
James ND, Bartus K, Grist J, Bennett DL, McMahon SB, Bradbury EJ . Conduction failure following spinal cord injury: functional and anatomical changes from acute to chronic stages. J Neurosci 2011; 31: 18543–18555.
Zhang Z, Krebs CJ, Guth L . Experimental analysis of progressive necrosis after spinal cord trauma in the rat: etiological role of the inflammatory response. Exp Neurol 1997; 143: 141–152.
Fitch MT, Doller C, Combs CK, Landreth GE, Silver J . Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci 1999; 19: 8182–8198.
Nelson E, Gertz SD, Rennels ML, Ducker TB, Blaumanis OR . Spinal cord injury. The role of vascular damage in the pathogenesis of central hemorrhagic necrosis. Arch Neurol 1977; 34: 332–333.
Tator CH, Fehlings MG . Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991; 75: 15–26.
Tator CH, Koyanagi I . Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg 1997; 86: 483–492.
Nemecek S . Morphological evidence of microcirculatory disturbances in experimental spinal cord trauma. Adv Neurol 1978; 20: 395–405.
Herzog A, Brosamle C . 'Semifree-floating' treatment: a simple and fast method to process consecutive sections for immunohistochemistry and neuronal tracing. J Neurosci Methods 1997; 72: 57–63.
Bresnahan JC . An electron-microscopic analysis of axonal alterations following blunt contusion of the spinal cord of the rhesus monkey (Macaca mulatta. J Neurol Sci 1978; 37: 59–82.
Casella GT, Bunge MB, Wood PM . Endothelial cell loss is not a major cause of neuronal and glial cell death following contusion injury of the spinal cord. Exp Neurol 2006; 202: 8–20.
Griffiths IR, McCulloch MC . Nerve fibres in spinal cord impact injuries. Part 1. Changes in the myelin sheath during the initial 5 weeks. J Neurol Sci 1983; 58: 335–349.
Tator CH, Rowed DW . Current concepts in the immediate management of acute spinal cord injuries. Can Med Assoc J 1979; 121: 1453–1464.
Liu XZ, Xu XM, Hu R, Du C, Zhang SX, McDonald JW et al. Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci 1997; 17: 5395–5406.
Zhang Z, Guth L . Experimental spinal cord injury: Wallerian degeneration in the dorsal column is followed by revascularization, glial proliferation, and nerve regeneration. Exp Neurol 1997; 147: 159–171.
Narayana P, Abbe R, Liu SJ, Johnston D . Does loss of gray- and white-matter contrast in injured spinal cord signify secondary injury? In vivo longitudinal MRI studies. Magn Reson Med 1999; 41: 315–320.
Weber T, Vroemen M, Behr V, Neuberger T, Jakob P, Haase A et al. In vivo high-resolution MR imaging of neuropathologic changes in the injured rat spinal cord. Am J Neuroradiol 2006; 27: 598–604.
Demediuk P, Lemke M, Faden AI . Spinal cord edema and changes in tissue content of Na+, K+, and Mg2+ after impact trauma in rats. Adv Neurol 1990; 52: 225–232.
Lemke M, Demediuk P, McIntosh TK, Vink R, Faden AI . Alterations in tissue Mg++, Na+ and spinal cord edema following impact trauma in rats. Biochem Biophys Res Commun 1987; 147: 1170–1175.
Lemke M, Faden AI . Edema development and ion changes in rat spinal cord after impact trauma: injury dose-response studies. J Neurotrauma 1990; 7: 41–54.
Sudo H, Taneichi H, Kaneda K . Secondary medulla oblongata involvement following middle cervical spinal cord injury associated with latent traumatic instability in a patient with ossification of the posterior longitudinal ligament. Spinal Cord 2006; 44: 126–129.
Ito T, Oyanagi K, Wakabayashi K, Ikuta F . Traumatic spinal cord injury: a neuropathological study on the longitudinal spreading of the lesions. Acta Neuropathol (Berl) 1997; 93: 13–18.
Hashizume Y, Iljima S, Kishimoto H, Hirano A . Pencil-shaped softening of the spinal cord. Pathologic study in 12 autopsy cases. Acta Neuropathol 1983; 61: 219–224.
Hinokuma K, Ohama E, Oyanagi K, Kakita A, Kawai K, Ikuta F . Syringomyelia. A neuropathological study of 18 autopsy cases. Acta Pathol Jpn 1992; 42: 25–34.
Oyanagi K, Yamazaki K, Hinokuma K, Ito F, Ikuta S . An autopsy case of intramedullary venous malformation of the spinal cord with spreading hematomyelia. Clin Neuropathol 1990; 9: 148–151.
Allen AR . Surgery of experimental lesions of spinal cord equivalent to crush injury of fracture dislocation of spinal column. A preliminary report. J Am Med Assoc 1911; 57: 878–880.
Yang DG, Li JJ, Gu R, Yang ML, Zhang X, Du LJ et al. Optimal time window of myelotomy in rats with acute traumatic spinal cord injury: a preliminary study. Spinal Cord 2013; 51: 673–678.
Hu AM, Li JJ, Sun W, Yang DG, Yang ML, Du LJ et al. Myelotomy reduces spinal cord edema and inhibits aquaporin-4 and aquaporin-9 expression in rats with spinal cord injury. Spinal Cord 2015; 53: 98–102.
Hall ED, Springer JE . Neuroprotection and acute spinal cord injury: a reappraisal. NeuroRx 2004; 1: 80–100.
Short DJ, El Masry WS, Jones PW . High dose methylprednisolone in the management of acute spinal cord injury - a systematic review from a clinical perspective. Spinal Cord 2000; 38: 273–286.
Gomes JA, Stevens RD, JJ3 Lewin, Mirski MA, Bhardwaj A . Glucocorticoid therapy in neurologic critical care. Crit Care Med 2005; 33: 1214–1224.
De Vivo P, Del Gaudio A, Ciritella P, Puopolo M, Chiarotti F, Mastronardi E . Hypertonic saline solution: a safe alternative to mannitol 18% in neurosurgery. Minerva Anestesiol 2001; 67: 603–611.
Forsyth LL, Liu-DeRyke X, Parker D Jr, Rhoney DH . Role of hypertonic saline for the management of intracranial hypertension after stroke and traumatic brain injury. Pharmacotherapy 2008; 28: 469–484.
Ziai WC, Toung TJ, Bhardwaj A . Hypertonic saline: first-line therapy for cerebral edema? J Neurol Sci 2007; 261: 157–166.
Legos JJ, Gritman KR, Tuma RF, Young WF . Coadministration of methylprednisolone with hypertonic saline solution improves overall neurological function and survival rates in a chronic model of spinal cord injury. Neurosurgery 2001; 49: 1427–1433.
Young WF, Rosenwasser RH, Vasthare US, Tuma RF . Preservation of post-compression spinal cord function by infusion of hypertonic saline. J Neurosurg Anesthesiol 1994; 6: 122–127.
Tuma RF, Vasthare US, Arfors KE, Young WF . Hypertonic saline administration attenuates spinal cord injury. J Trauma 1997; 42: S54–S60.
Spera PA, Vasthare US, Tuma RF, Young WF . The effects of hypertonic saline on spinal cord blood flow following compression injury. Acta Neurochir (Wien) 2000; 142: 811–817.
Acknowledgements
This work has been supported by project APVV 14-0847 and project NEUREG, ITMS: 26220120063.
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Tomko, P., Farkaš, D., Čížková, D. et al. Longitudinal enlargement of the lesion after spinal cord injury in the rat: a consequence of malignant edema?. Spinal Cord 55, 255–263 (2017). https://doi.org/10.1038/sc.2016.133
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DOI: https://doi.org/10.1038/sc.2016.133
