Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury

Laboratory investigation

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Spinal cord injury (SCI) often results in considerable permanent neurological impairment, and unfortunately, the successful translation of effective treatments from laboratory models to human patients is lacking. This may be partially attributed to differences in anatomy, physiology, and scale between humans and rodent models. One potentially important difference between the rodent and human spinal cord is the presence of a significant CSF volume within the intrathecal space around the human cord. While the CSF may “cushion” the spinal cord, pressure waves within the CSF at the time of injury may contribute to the extent and severity of the primary injury. The objective of this study was to develop a model of contusion SCI in a miniature pig and establish the feasibility of measuring spinal CSF pressure during injury.


A custom weight-drop device was used to apply thoracic contusion SCI to 17 Yucatan miniature pigs. Impact load and velocity were measured. Using fiber optic pressure transducers implanted in the thecal sac, CSF pressures resulting from 2 injury severities (caused by 50-g and 100-g weights released from a 50-cm height) were measured.


The median peak impact loads were 54 N and 132 N for the 50-g and 100-g injuries, respectively. At a nominal 100 mm from the injury epicenter, the authors observed a small negative pressure peak (median −4.6 mm Hg [cranial] and −5.8 mm Hg [caudal] for 50 g; −27.6 mm Hg [cranial] and −27.2 mm Hg [caudal] for 100 g) followed by a larger positive pressure peak (median 110.5 mm Hg [cranial] and 77.1 mm Hg [caudal] for 50 g; 88.4 mm Hg [cranial] and 67.2 mm Hg [caudal] for 100 g) relative to the preinjury pressure. There were no significant differences in peak pressure between the 2 injury severities or the caudal and cranial transducer locations.


A new model of contusion SCI was developed to measure spinal CSF pressures during the SCI event. The results suggest that the Yucatan miniature pig is an appropriate model for studying CSF, spinal cord, and dura interactions during injury. With further development and characterization it may be an appropriate in vivo largeanimal model of SCI to answer questions regarding pathological changes, therapeutic safety, or treatment efficacy, particularly where humanlike dimensions and physiology are important.

Abbreviations used in this paper:IM = intramuscularly; SCI = spinal cord injury.

Article Information

Address correspondence to: Claire F. Jones, Ph.D., Biomechanics Laboratory, Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, British Columbia V5Z 1M9, Canada. email:

Please include this information when citing this paper: published online April 20, 2012; DOI: 10.3171/2012.3.SPINE11970.

© AANS, except where prohibited by US copyright law.



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    Photograph of the components of the modified weight-drop injury device. Inset: Close-up view of the load cell installed within the weight base, above the spherical impactor tip.

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    Schematic of front view (left) and side view (right) of the weight-drop device installed over 4 vertebrae (not to scale).

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    Upper: Photograph showing the surgical site, with 4 pressure transducers implanted intrathecally, a widened laminectomy at the injury site, and pedicle screws in T-9 and T-12. Lower: The same photograph with an overlay indicating locations of pressure transducer tips relative to the injury site (circle). The 2 “near” transducers were only implanted in 2 of the Group C animals.

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    Graphs showing CSF pressure (CSFP) measured at the cranial-far (A) and caudal-far (B) transducers and load (C) for the Group B (50-g injury) animals. Zero time is arbitrarily aligned at caudal-far = ±3 mm Hg. There were no significant differences between the peak pressures (positive and negative) measured at the cranial-far and caudal-far locations. The early rise of the impact force, relative to the CSF pressure, for P1219 may indicate contact between the impactor and the sides of the laminectomy prior to dura contact. ms = milliseconds.

  • View in gallery

    Graphs showing CSF pressure measured at the cranial-far (A) and caudal-far (B) transducers and load (C) for the Group C (100-g injury) animals. Zero time is arbitrarily aligned at caudal-far = ±3 mm Hg. There were no significant differences between the peak pressures (positive and negative) measured at the cranial-far and caudal-far locations. There was considerable variability in the pressure profiles; for example, P1242 showed very little pressure change while P1264 exhibited a large fluctuation, yet the impact force profiles are fairly similar.

  • View in gallery

    Graphs showing CSF pressures for the 2 tests performed in Group C in which 2 “near” transducers were implanted (top: P1242; bottom: P1262). The pressures at the “near” location exceeded the upper range of the pressure transducers.



Aito SEl Masry WSGerner HJLorenzo NDPellicanò GD'Andrea M: Ascending myelopathy in the early stage of spinal cord injury. Spinal Cord 37:6176231999


Albin MSHung TKBrown TDJannetta PJBunegin LAlbin RL: Experimental spinal cord injury biomechanics. Neuroscience Abstracts 1:6971975


Albin MSWhite RJAcosta-Rua GYashon D: Study of functional recovery produced by delayed localized cooling after spinal cord injury in primates. J Neurosurg 29:1131201968


Babu RSPeriasamy PVaradamurthy SSethuraman OSNamasivayam A: Locomotor behavior of bonnet macaques after spinal cord injury. Mot Contr 11:71852007


Barth KNOnesti STKrauss WESolomon RA: A simple and reliable technique to monitor intracranial pressure in the rat: technical note. Neurosurgery 30:1381401992


Belanger EPicard CLacerte DLavallee PLevi AD: Subacute posttraumatic ascending myelopathy after spinal cord injury. Report of three cases. J Neurosurg 93:2 Suppl2942992000


Belytschko TPrivitzer E: Refinement and Validation of the Three-Dimensional Head-Spine Model Wright-Patterson Air Force Base, OhioAerospace Medical Research Laboratory1978. ( [Accessed March 23 2012]


Bernards CM: Cerebrospinal fluid and spinal cord distribution of baclofen and bupivacaine during slow intrathecal infusion in pigs. Anesthesiology 105:1691782006


Bernards CMAkers T: Effect of postinjury intravenous or intrathecal methylprednisolone on spinal cord excitatory amino-acid release, nitric oxide generation, PGE2 synthesis, and myeloperoxidase content in a pig model of acute spinal cord injury. Spinal Cord 44:5946042006


Blight ARDecrescito V: Morphometric analysis of experimental spinal cord injury in the cat: the relation of injury intensity to survival of myelinated axons. Neuroscience 19:3213411986


Bozkus HCrawford NRChamberlain RHValenzuela TDEspinoza AYüksel Z: Comparative anatomy of the porcine and human thoracic spines with reference to thoracoscopic surgical techniques. Surg Endosc 19:165216652005


Broome JRDick EJ Jr: Neurological decompression illness in swine. Aviat Space Environ Med 67:2072131996


Budgell BSBolton PS: Cerebrospinal fluid pressure in the anesthetized rat. J Manipulative Physiol Ther 30:3513562007


Busscher IPloegmakers JJVerkerke GJVeldhuizen AG: Comparative anatomical dimensions of the complete human and porcine spine. Eur Spine J 19:110411142010


Carlson GDOliff HSGorden CSmith JAnderson PA: Cerebral spinal fluid pressure: effects of body position and lumbar subarachnoid drainage in a canine model. Spine 28:1191222003


Chavko MKoller WAPrusaczyk WKMcCarron RM: Measurement of blast wave by a miniature fiber optic pressure transducer in the rat brain. J Neurosci Methods 159:2772812007


Clausen FHillered L: Intracranial pressure changes during fluid percussion, controlled cortical impact and weight drop injury in rats. Acta Neurochir (Wien) 147:7757802005


Cornish RBlumbergs PCManavis JScott GJones NRReilly PL: Topography and severity of axonal injury in human spinal cord trauma using amyloid precursor protein as a marker of axonal injury. Spine (Phila Pa 1976) 25:122712332000


Czeiter EPal JKovesdi EBukovics PLuckl JDoczi T: Traumatic axonal injury in the spinal cord evoked by traumatic brain injury. J Neurotrauma 25:2052132008


Daniell HBFrancis WWLee WADucker TB: A method of quantitating injury inflicted in acute spinal cord studies. Paraplegia 13:1371421975


Dick EJ JrBroome JRHayward IJ: Acute neurologic decompression illness in pigs: lesions of the spinal cord and brain. Lab Anim Sci 47:50571997


Dickerson JWTDobbing J: Prenatal and postnatal growth and development of the central nervous system of the pig. Proc R Soc Lond B Biol Sci 166:3843951967


Dietrich WD: Confirming an experimental therapy prior to transfer to humans: what is the ideal?. J Rehabil Res Dev 40:4 Suppl 163692003


Dohrmann GJPanjabi MM: “Standardized” spinal cord trauma: biomechanical parameters and lesion volume. Surg Neurol 6:2632671976


Dohrmann GJPanjabi MMBanks D: Biomechanics of experimental spinal cord trauma. J Neurosurg 48:99310011978


Ducker TBSalcman MDaniell HB: Experimental spinal cord trauma, III: Therapeutic effect of immobilization and pharmacologic agents. Surg Neurol 10:71761978


Ducker TBSalcman MPerot PL JrBallantine D: Experimental spinal cord trauma, I: Correlation of blood flow, tissue oxygen and neurologic status in the dog. Surg Neurol 10:60631978


Duhaime AC: Large animal models of traumatic injury to the immature brain. Dev Neurosci 28:3803872006


Eichberger ADarok MSteffan HLeinzinger PEBoström OSvensson MY: Pressure measurements in the spinal canal of post-mortem human subjects during rear-end impact and correlation of results to the neck injury criterion. Accid Anal Prev 32:2512602000


Etz CDHomann TMLuehr MKari FAWeisz DJKleinman G: Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries. Eur J Cardiothorac Surg 33:103010382008


Fialho SALumb WVScott RJ: Pneumatically powered vertebral displacement device for dogs. Am J Vet Res 43:125412571982


Ford RW: A reproducible spinal cord injury model in the cat. J Neurosurg 59:2682751983


Gellad FRao KCJoseph PMVigorito RD: Morphology and dimensions of the thoracic cord by computer-assisted metrizamide myelography. AJNR Am J Neuroradiol 4:6146171983


Gerber AMCorrie WS: Effect of impounder contact area on experimental spinal cord injury. J Neurosurg 51:5395421979


Greaves CYGadala MSOxland TR: A three-dimensional finite element model of the cervical spine with spinal cord: an investigation of three injury mechanisms. Ann Biomed Eng 36:3964052008


Greenfield JC JrRembert JCTindall GT: Transient changes in cerebral vascular resistance during the Valsalva maneuver in man. Stroke 15:76791984


Hadley MNSonntag VKRekate HLMurphy A: The infant whiplash-shake injury syndrome: a clinical and pathological study. Neurosurgery 24:5365401989


Hall RMOakland RJWilcox RKBarton DC: Spinal cord-fragment interactions following burst fracture: an in vitro model. J Neurosurg Spine 5:2432502006


Hillyer JEJones CLee JHildebrandt RGray GGodbey T: Development of a chronic porcine model of spinal cord injury. ({081F7976-E4CD-4F3D-A0AF-E8387992A658}) [Accessed March 29 2012]


Hung TKAlbin MSBrown TDBunegin LAlbin RJannetta PJ: Biomechanical responses to open experimental spinal cord injury. Surg Neurol 4:2712761975


Hung TKLin HSAlbin MSBunegin LJannetta PJ: The standardization of experimental impact injury to the spinal cord. Surg Neurol 11:4704771979


Iwanami AYamane JKatoh HNakamura MMomoshima SIshii H: Establishment of graded spinal cord injury model in a nonhuman primate: the common marmoset. J Neurosci Res 80:1721812005


Jones CFKroeker SGCripton PAHall RM: The effect of cerebrospinal fluid on the biomechanics of spinal cord: an ex vivo bovine model using bovine and physical surrogate spinal cord. Spine (Phila Pa 1976) 33:E580E5882008


Kameyama THashizume YSobue G: Morphologic features of the normal human cadaveric spinal cord. Spine 21:128512901996


Kato KFujimura MNakagawa ASaito AOhki TTakayama K: Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosis mediated by a caspase-dependent pathway. J Neurosurg 106:6676762007


Kaur CSingh JLim MKNg BLYap EPLing EA: The response of neurons and microglia to blast injury in the rat brain. Neuropathol Appl Neurobiol 21:3693771995


Klarica MRados MDraganic PErceg GOreskovic DMaraković J: Effect of head position on cerebrospinal fluid pressure in cats: comparison with artificial model. Croat Med J 47:2332382006


Ko HYPark JHShin YBBaek SY: Gross quantitative measurements of spinal cord segments in human. Spinal Cord 42:35402004


Koenig GDohrmann GJ: Histopathological variability in ‘standardised’ spinal cord trauma. J Neurol Neurosurg Psychiatry 40:120312101977


Koozekanani SHVise WMHashemi RMMcGhee RB: Possible mechanisms for observed pathophysiological variability in experimental spinal cord injury by the method of Allen. J Neurosurg 44:4294341976


Krave UHöjer SHansson HA: Transient, powerful pressures are generated in the brain by a rotational acceleration impulse to the head. Eur J Neurosci 21:287628822005


Kuluz JSamdani ABenglis DGonzalez-Brito MSolano JPRamirez MA: Pediatric spinal cord injury in infant piglets: description of a new large animal model and review of the literature. J Spinal Cord Med 33:43572010


Kumar AKumar JGarg MFarooque KGamanagatti SSharma V: Posttraumatic subacute ascending myelopathy in a 24-year-old male patient. Emerg Radiol 17:2492522010


Kuruvilla ATheodore DRAbraham J: Changes in norepinephrine and histamine in monkey spinal cords traumatized by weight drop and compression. Cent Nerv Syst Trauma 2:61711985


Kusaka GCalvert JWSmelley CNanda AZhang JH: New lumbar method for monitoring cerebrospinal fluid pressure in rats. J Neurosci Methods 135:1211272004


Kwon BKHillyer JTetzlaff W: Translational research in spinal cord injury: a survey of opinion from the SCI community. J Neurotrauma 27:21332010


Kwon BKOkon EBTsai EBeattie MSBresnahan JCMagnuson DK: A grading system to evaluate objectively the strength of pre-clinical data of acute neuroprotective therapies for clinical translation in spinal cord injury. J Neurotrauma 28:152515432011


Lammertse DTuszynski MHSteeves JDCurt AFawcett JWRask C: Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design. Spinal Cord 45:2322422007


Lee SHChung YNKim YHKim YJPark JPKwon DK: Effects of human neural stem cell transplantation in canine spinal cord hemisection. Neurol Res 31:99610022009


Maikos JTQian ZMetaxas DShreiber DI: Finite element analysis of spinal cord injury in the rat. J Neurotrauma 25:7958162008


Molt JTNelson LRPoulos DABourke RS: Analysis and measurement of some sources of variability in experimental spinal cord trauma. J Neurosurg 50:7847911979


Moochhala SMMd SLu JTeng CHGreengrass C: Neuroprotective role of aminoguanidine in behavioral changes after blast injury. J Trauma 56:3934032004


Örtengren THansson HALövsund PSvensson MYSuneson ASäljö A: Membrane leakage in spinal ganglion nerve cells induced by experimental whiplash extension motion: a study in pigs. J Neurotrauma 13:1711801996


Owen JHNaito MBridwell KH: Relationship among level of distraction, evoked potentials, spinal cord ischemia and integrity, and clinical status in animals. Spine (Phila Pa 1976) 15:8528571990


Panjabi MMKifune MWen LArand MOxland TRLin RM: Dynamic canal encroachment during thoracolumbar burst fractures. J Spinal Disord 8:39481995


Papakostas JCMatsagas MIToumpoulis IKMalamou-Mitsi VDPappa LSGkrepi C: Evolution of spinal cord injury in a porcine model of prolonged aortic occlusion. J Surg Res 133:1591662006


Persson CMcLure SWSummers JHall RM: The effect of bone fragment size and cerebrospinal fluid on spinal cord deformation during trauma: an ex vivo study. Laboratory investigation. J Neurosurg Spine 10:3153232009


Petras JMBauman RAElsayed NM: Visual system degeneration induced by blast overpressure. Toxicology 121:41491997


Säljö AArrhén FBolouri HMayorga MHamberger A: Neuropathology and pressure in the pig brain resulting from low-impulse noise exposure. J Neurotrauma 25:139714062008


Säljö ABao FHaglid KGHansson HA: Blast exposure causes redistribution of phosphorylated neurofilament subunits in neurons of the adult rat brain. J Neurotrauma 17:7197262000


Säljö ABao FHamberger AHaglid KGHansson HA: Exposure to short-lasting impulse noise causes microglial and astroglial cell activation in the adult rat brain. Pathophysiology 8:1051112001


Säljö ABao FJingshan SHamberger AHansson HAHaglid KG: Exposure to short-lasting impulse noise causes neuronal c-Jun expression and induction of apoptosis in the adult rat brain. J Neurotrauma 19:9859912002


Säljö ABao FShi JHamberger AHansson HAHaglid KG: Expression of c-Fos and c-Myc and deposition of beta-APP in neurons in the adult rat brain as a result of exposure to short-lasting impulse noise. J Neurotrauma 19:3793852002


Säljö ABolouri HMayorga MSvensson BHamberger A: Low-level blast raises intracranial pressure and impairs cognitive function in rats: prophylaxis with processed cereal feed. J Neurotrauma 27:3833892010


Salzano RP JrEllison LHAltonji PFRichter JDeckers PJ: Regional deep hypothermia of the spinal cord protects against ischemic injury during thoracic aortic cross-clamping. Ann Thorac Surg 57:65711994


Shannon PSmith CRDeck JAng LCHo MBecker L: Axonal injury and the neuropathology of shaken baby syndrome. Acta Neuropathol 95:6256311998


Sheng SRWang XYXu HZZhu GQZhou YF: Anatomy of large animal spines and its comparison to the human spine: a systematic review. Eur Spine J 19:46562010


Singer BATresser NJFrank JAMcFarland HFBiddison WE: Induction of experimental allergic encephalomyelitis in the NIH minipig. J Neuroimmunol 105:7192000


Skinner SATransfeldt EEMehbod AAMullan JCPerra JH: Electromyography detects mechanically-induced supra-segmental spinal motor tract injury: review of decompression at spinal cord level. Clin Neurophysiol 120:7547642009


Strauch JTLauten AZhang NWahlers TGriepp RB: Anatomy of spinal cord blood supply in the pig. Ann Thorac Surg 83:213021342007


Svensson MYAldman BHansson HALövsund Seeman TSuneson A: Pressure effects in the spinal canal during whiplash extension motion: a possible cause of injury to the cervical spinal ganglia. Proceedings of the International Research Committee on the Biomechanics of Impacts (IRCOBI)Eindhoven, The Netherlands1993. ( [Accessed March 26 2012]


Svetlov SIPrima VKirk DRGutierrez HCurley KCHayes RL: Morphologic and biochemical characterization of brain injury in a model of controlled blast overpressure exposure. J Trauma 69:7958042010


Swindle MM: Swine in the Laboratory: Surgery Anesthesia Imaging and Experimental Techniques ed 2New YorkCRC Press2007


Tator CH: Review of treatment trials in human spinal cord injury: issues, difficulties, and recommendations. Neurosurgery 59:9579872006


Wadouh FMetzger HArndt CFHartmann MSchywalsky MHetzer R: Response of spinal cord oxygen tension to aortic occlusion. Adv Exp Med Biol 180:7317401984


Watson CPaxinos GKayalioglu G: Christopher & Dana Reeve Foundation: The Spinal Cord: A Christopher and Dana Reeve Foundation Text and Atlas AmsterdamElsevier/Academic Press2009


Wennerstrand JJönsson AArvebo E: Mechanical and histological effects of transverse impact on the canine spinal cord. J Biomech 11:3153311978


Wilcox RKAllen DJHall RMLimb DBarton DCDickson RA: A dynamic investigation of the burst fracture process using a combined experimental and finite element approach. Eur Spine J 13:4814882004


Williams B: Simultaneous cerebral and spinal fluid pressure recordings. I. Technique, physiology, and normal results. Acta Neurochir (Wien) 58:1671851981


Yeo JDPayne WHinwood BKidman AD: The experimental contusion injury of the spinal cord in sheep. Paraplegia 12:2792981975


Zaaroor MKósa GPeri-Eran AMaharil IShoham MGoldsher D: Morphological study of the spinal canal content for subarachnoid endoscopy. Minim Invasive Neurosurg 49:2202262006


Zurita MVaquero JBonilla CSantos MDe Haro JOya S: Functional recovery of chronic paraplegic pigs after autologous transplantation of bone marrow stromal cells. Transplantation 86:8458532008




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