Air Gun Impactor—A Novel Model of Graded White Matter Spinal Cord Injury in Rodents

Abstract

Understanding mechanisms of spinal cord injury and repair requires a reliable experimental model. We have developed a new device that produces a partial damage of spinal cord white matter by means of a precisely adjusted stream of air applied under high pressure. This procedure is less invasive than standard contusion or compression models and does not require surgical removal of vertebral bones. We investigated the effects of spinal cord injury made with our device in 29 adult rats, applying different experimental parameters. The rats were divided into three groups in respect to the applied force of the blast wave. Functional outcome and histopathological effects of the injury were analyzed during 12-week follow-up. The lesions were also examined by means of magnetic resonance imaging (MRI) scans. The weakest stimulus produced transient hindlimb paresis with no cyst visible in spinal cord MRI scans, whereas the strongest was associated with permanent neurological deficit accompanied by pathological changes resembling posttraumatic syringomyelia. Obtained data revealed that our apparatus provided a spinal cord injury animal model with structural changes very similar to that present in patients after moderate spinal cord trauma.

Keywords

spinal cord injury - animal model - trauma - syringomyelia

• References

• 1 Sun F, He Z. Neuronal intrinsic barriers for axon regeneration in the adult CNS. Curr Opin Neurobiol 2010; 20: 510-518
• 2 Falci SP, Indeck C, Lammertse DP. Posttraumatic spinal cord tethering and syringomyelia: surgical treatment and long-term outcome. J Neurosurg Spine 2009; 11: 445-460
• 3 Steuer I, Guertin PA. Spinal cord injury research in mice: 2008 review. ScientificWorldJournal 2009; 9: 490-498
• 4 Schwab JM, Brechtel K, Mueller CA , et al. Experimental strategies to promote spinal cord regeneration—an integrative perspective. Prog Neurobiol 2006; 78: 91-116
• 5 Tator CH. Update on the pathophysiology and pathology of acute spinal cord injury. Brain Pathol 1995; 5: 407-413
• 6 Tator CH. Biology of neurological recovery and functional restoration after spinal cord injury. Neurosurgery 1998; 42: 696-707 , discussion 707–708
• 7 Stichel CC, Müller HW. The CNS lesion scar: new vistas on an old regeneration barrier. Cell Tissue Res 1998; 294: 1-9
• 8 Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull 1999; 49: 377-391
• 9 Grimpe B, Silver J. The extracellular matrix in axon regeneration. Prog Brain Res 2002; 137: 333-349
• 10 Fehlings MG, Tator CH. The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury. Exp Neurol 1995; 132: 220-228
• 11 Akhtar AZ, Pippin JJ, Sandusky CB. Animal models in spinal cord injury: a review. Rev Neurosci 2008; 19: 47-60
• 12 Allen A. Surgery of experimental lesion of spinal cord equivalent to crush injury. JAMA 1911; 37: 878-880
• 13 Wrathall JR, Pettegrew RK, Harvey F. Spinal cord contusion in the rat: production of graded, reproducible, injury groups. Exp Neurol 1985; 88: 108-122
• 14 Dohrmann GJ, Panjabi MM. “Standardized” spinal cord trauma: biomechanical parameters and lesion volume. Surg Neurol 1976; 6: 263-267
• 15 Gensel JC, Tovar CA, Hamers FP, Deibert RJ, Beattie MS, Bresnahan JC. Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats. J Neurotrauma 2006; 23: 36-54
• 16 Rivlin AS, Tator CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 1978; 10: 38-43
• 17 von Euler M, Seiger A, Sundström E. Clip compression injury in the spinal cord: a correlative study of neurological and morphological alterations. Exp Neurol 1997; 145: 502-510
• 18 Blight AR. Morphometric analysis of a model of spinal cord injury in guinea pigs, with behavioral evidence of delayed secondary pathology. J Neurol Sci 1991; 103: 156-171
• 19 Gruner JA, Yee AK, Blight AR. Histological and functional evaluation of experimental spinal cord injury: evidence of a stepwise response to graded compression. Brain Res 1996; 729: 90-101
• 20 Onifer SM, Rabchevsky AG, Scheff SW. Rat models of traumatic spinal cord injury to assess motor recovery. ILAR J 2007; 48: 385-395
• 21 LaPlaca MC, Simon CM, Prado GR, Cullen DK. CNS injury biomechanics and experimental models. Prog Brain Res 2007; 161: 13-26
• 22 Anderson TE. A controlled pneumatic technique for experimental spinal cord contusion. J Neurosci Methods 1982; 6: 327-333
• 23 Noyes DH. Electromechanical impactor for producing experimental spinal cord injury in animals. Med Biol Eng Comput 1987; 25: 335-340
• 24 Scheff SW, Rabchevsky AG, Fugaccia I, Main JA, Lumpp Jr JE. Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma 2003; 20: 179-193
• 25 Choo AM-T, Liu J, Liu Z, Dvorak M, Tetzlaff W, Oxland TR. Modeling spinal cord contusion, dislocation, and distraction: characterization of vertebral clamps, injury severities, and node of Ranvier deformations. J Neurosci Methods 2009; 181: 6-17
• 26 Marques SA, Garcez VF, Del Bel EA, Martinez AMB. A simple, inexpensive and easily reproducible model of spinal cord injury in mice: morphological and functional assessment. J Neurosci Methods 2009; 177: 183-193
• 27 da Costa ES, Carvalho AL, Martinez AMB, De-Ary-Pires B, Pires-Neto MA, de Ary-Pires R. Strapping the spinal cord: an innovative experimental model of CNS injury in rats. J Neurosci Methods 2008; 170: 130-139
• 28 Gzik M, Tejszerska D, Bobrowski M , et al. A new non-laminectomy model of the spinal cord injury: pressure impactor. Acta Bioeng Biomech 2006; 8: 89-95
• 29 de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol 1982; 77: 634-643
• 30 Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995; 12: 1-21
• 31 Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Morshead CM, Fehlings MG. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci 2006; 26: 3377-3389
• 32 Hemley SJ, Biotech B, Tu J, Stoodley MA. Role of the blood-spinal cord barrier in posttraumatic syringomyelia. J Neurosurg Spine 2009; 11: 696-704
• 33 Maxwell WL. Histopathological changes at central nodes of Ranvier after stretch-injury. Microsc Res Tech 1996; 34: 522-535
• 34 Squier MV, Lehr RP. Post-traumatic syringomyelia. J Neurol Neurosurg Psychiatry 1994; 57: 1095-1098
• 35 Kearney PA, Ridella SA, Viano DC, Anderson TE. Interaction of contact velocity and cord compression in determining the severity of spinal cord injury. J Neurotrauma 1988; 5: 187-208
• 36 Schrimsher GW, Reier PJ. Forelimb motor performance following dorsal column, dorsolateral funiculi, or ventrolateral funiculi lesions of the cervical spinal cord in the rat. Exp Neurol 1993; 120: 264-276
• 37 Schucht P, Raineteau O, Schwab ME, Fouad K. Anatomical correlates of locomotor recovery following dorsal and ventral lesions of the rat spinal cord. Exp Neurol 2002; 176: 143-153
• 38 Cameron AA, Smith GM, Randall DC, Brown DR, Rabchevsky AG. Genetic manipulation of intraspinal plasticity after spinal cord injury alters the severity of autonomic dysreflexia. J Neurosci 2006; 26: 2923-2932