Subscribe to RSS
DOI: 10.1055/s-0031-1271732
© Georg Thieme Verlag KG Stuttgart · New York
Closed Traumatic Brain Injury Model in Sheep Mimicking High-Velocity, Closed Head Trauma in Humans
Publication History
Publication Date:
07 July 2011 (online)
Abstract
To date, there are only a few, non-evidence based, cerebroprotective therapeutic strategies for treatment and, accordingly, for prevention of secondary brain injuries following severe closed head trauma. In order to develop new therapy strategies, existing realistic animal models need to be advanced. The objective is to bridge standardized small animal models and actual patient medical care, since the results of experimental small animal studies often cannot be transferred to brain-injured humans. For improved standardization of high-velocity trauma, new trauma devices for initiating closed traumatic brain injury in sheep were developed. The following new devices were tested: 1. An anatomically shaped rubber bolt with an integrated oscillation absorber for prevention of skull fractures; 2. Stationary mounting of the bolt to guarantee stable experimental conditions; 3. Varying degrees of trauma severity, i. e., mild and severe closed traumatic brain injury, using different cartridges; and 4. Trauma analysis via high-speed video recording. Peritraumatic measurements of intracranial pressure, brain tissue pH, brain tissue oxygen, and carbon dioxide pressure, as well as neurotransmitter concentrations were performed. Cerebral injuries were documented with magnetic resonance imaging and compared to neuropathological results. Due to the new trauma devices, skull fractures were prevented. The high-speed video recording documented a realistic trauma mechanism for a car accident. Enhancement of extracellular glutamate, aspartate, and gamma amino butyric acid concentrations began 60 min after the trauma. Magnetic resonance imaging and neuropathological results showed characteristic injury patterns of mild, and severe, closed traumatic brain injury. The severe, closed traumatic brain injury group showed diffuse axonal injuries, traumatic subarachnoid hemorrhage, and hemorrhagic contusions with inconsistent distribution among the animals. The model presented here achieves a gain in standardization of severe, closed traumatic brain injury by increasing approximation to reality. The still existent heterogeneity of brain pathology mimics brain changes observed in patients after high-energy trauma. This model seems to close the gap between experimental small animal models and clinical studies. However, further investigations are needed to evaluate if this model can be used for testing new therapeutic strategies for these patients.
Key words
closed traumatic brain injury - experimental animal model - magnetic resonance imaging - multiparametric cerebral monitoring - sheep
References
- 1 Stubbe HD, Greiner C, Van Aken H. et al . Cerebral vascular and metabolic response to sustained systemic inflammation in ovine traumatic brain injury. J Cereb Blood Flow Metab. 2004; 24 (12) 1400-1408
-
2
Centers for Disease Control and Prevention, Department of Health and Human Services
.
Facts about Traumatic Brain Injury [Internet] CDC; USA. www.edc.gov
2006;
- 3 Bullock MR, Lyeth BG, Muizelaar JP. Current status of neuroprotection trials for traumatic brain injury: lessons from animal models and clinical studies. Neurosurgery. 1999; 45 (2) 207-217 discussion 217–220
- 4 Doppenberg EM, Choi SC, Bullock R. Clinical trials in traumatic brain injury: lessons for the future. J Neurosurg Anesthesiol. 2004; 16 (1) 87-94
- 5 Gennarelli TA. Animate models of human head injury. J Neurotrauma. 1994; 11 (4) 357-368
- 6 Cernak I. Animal models of head trauma. NeuroRx. 2005; 2 (3) 410-422
- 7 Anderson RW, Brown CJ, Blumbergs PC. et al . Impact mechanics and axonal injury in a sheep model. J Neurotrauma. 2003; 20 (10) 961-974
- 8 Zhang L, Yang KH, King AI. Biomechanics of neurotrauma. Neurol Res. 2001; 23 (2–3) 144-156
- 9 Ommaya AK, Hirsch AE. Tolerances for cerebral concussion from head impact and whiplash in primates. J Biomech. 1971; 4 (1) 13-21
- 10 Ewing C, Thomas D, Lustick L. et al . The effect of the initial position of the head and neck to -Gx impact acceleration. In Proceedings 19th Stapp car crash conference, Nov. 17–20, 1975; 487-512
- 11 Gennarelli TA, Thibault LE, Adams JH. et al . Diffuse axonal injury and traumatic coma in the primate. Ann Neurol. 1982; 12 (6) 564-574
- 12 Gennarelli TA. Head injury in man and experimental animals: clinical aspects. Acta Neurochir Suppl. 1983; 32 1-13
- 13 Finnie JW, Manavis J, Summersides GE. et al . Brain damage in pigs produced by impact with a non-penetrating captive bolt pistol. Aust Vet J. 2003; 81 (3) 159-164
- 14 Finnie JW, Blumbergs PC. Traumatic brain injury. Vet Pathol. 2002; 39 (6) 679-689
- 15 Gennarelli TA, Adams JH, Graham DI. Acceleration induced head injury in the monkey. I. The model, its mechanical and physiological correlates. Acta Neuropathol Suppl. 1981; 7 23-25
- 16 Adams JH, Graham DI, Gennarelli TA. Acceleration induced head injury in the monkey. II. Neuropathology. Acta Neuropathol Suppl. 1981; 7 26-28
- 17 Piper I. Intracranial Pressure and Elastance. In: Reilly P, Bullock R, editors Head Injury: Pathophysiology and Management of Severe Closed Head Injury London, Chapman & Hall; 1997: 101-120
- 18 Doppenberg EM, Zauner A, Watson JC. et al . Determination of the ischemic threshold for brain oxygen tension. Acta Neurochir Suppl. 1998; 71 166-169
- 19 Zauner A, Clausen T, Alves OL. et al . Cerebral metabolism after fluid-percussion injury and hypoxia in a feline model. J Neurosurg. 2002; 97 (3) 643-649
- 20 Menzel M, Rieger A, Roth S. et al . Comparison between continuous brain tissue pO2, pCO2, pH, and temperature and simultaneous cerebrovenous measurement using a multisensor probe in a porcine intracranial pressure model. J Neurotrauma. 1998; 15 (4) 265-276
- 21 Nortje J, Gupta AK. The role of tissue oxygen monitoring in patients with acute brain injury. Br J Anaesth. 2006; 97 (1) 95-106
- 22 Clausen T, Khaldi A, Zauner A. et al . Cerebral acid-base homeostasis after severe traumatic brain injury. J Neurosurg. 2005; 103 (4) 597-607
- 23 Soukup J, Zauner A, Doppenberg EM. et al . Relationship between brain temperature, brain chemistry and oxygen delivery after severe human head injury: the effect of mild hypothermia. Neurol Res. 2002; 24 (2) 161-168
- 24 Nilsson P, Hillered L, Ponten U. et al . Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab. 1990; 10 (5) 631-637
- 25 Bullock R, Zauner A, Woodward JJ. et al . Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg. 1998; 89 (4) 507-518
- 26 Engstrom M, Polito A, Reinstrup P. et al . Intracerebral microdialysis in severe brain trauma: the importance of catheter location. J Neurosurg. 2005; 102 (3) 460-469
- 27 van Landeghem FK, Stover JF, Bechmann I. et al . Early expression of glutamate transporter proteins in ramified microglia after controlled cortical impact injury in the rat. Glia. 2001; 35 (3) 167-179
- 28 Hlatky R, Furuya Y, Valadka AB. et al . Comparison of microdialysate arginine and glutamate levels in severely head-injured patient. Acta Neurochir Suppl. 2002; 81 347-349
- 29 Storck T, Schulte S, Hofmann K. et al . Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. Proc Natl Acad Sci USA. 1992; 89 (22) 10955-10959
- 30 Kanthan R, Shuaib A. Clinical evaluation of extracellular amino acids in severe head trauma by intracerebral in vivo microdialysis. J Neurol Neurosurg Psychiatry. 1995; 59 (3) 326-327
- 31 Gallagher CN, Hutchinson PJ, Pickard JD. Neuroimaging in trauma. Curr Opin Neurol. 2007; 20 (4) 403-409
- 32 Keidel M, Rieschke P, Stude P. et al . Antinociceptive reflex alteration in acute posttraumatic headache following whiplash injury. Pain. 2001; 92 (3) 319-326
- 33 Lighthall JW, Dixon CE, Anderson TE. Experimental models of brain injury. J Neurotrauma. 1989; 6 (2) 83-97
- 34 Morales DM, Marklund N, Lebold D. et al . Experimental models of traumatic brain injury: do we really need to build a better mousetrap?. Neuroscience. 2005; 136 (4) 971-989
- 35 Povlishock JT, Hayes RL, Michel ME. et al . Workshop on animal models of traumatic brain injury. J Neurotrauma. 1994; 11 (6) 723-732
- 36 Statler KD, Jenkins LW, Dixon CE. et al . The simple model versus the super model: translating experimental traumatic brain injury research to the bedside. J Neurotrauma. 2001; 18 (11) 1195-1206
Correspondence
A.-C. Grimmelt
University of Münster
Department of Neurosurgery
Albert-Schweizer-Straße 33
48149 Münster
Germany
Phone: +49/0251/83 47 472
Fax: +49/0251/83 47 47
Email: ann-christin.grimmelt@med.uni-muenchen.de