A controlled cortical impact model of traumatic brain injury in the rat

Dixon, C. Edward; Clifton, Guy L.; Lighthall, James W.; Yaghmai, Amy A.; Hayes, Ronald L.

Affiliations

¹Department of Rehabilitation Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA (U.S.A.)

²Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA (U.S.A.)

³Biomedical Science Department, General Motors Research Laboratories, Warren, MI (U.S.A.)

⁴Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA (U.S.A.)

Abstract and keywords

Controlled cortical impact models produce brain injury by using a pneumatic impactor to impact exposed brain. This study systematically examined the effects of varying magnitudes of controlled cortical impact to the rat brain on neurological, cardiovascular, and histopathological variables. As the magnitude of injury increased, the duration of suppression of somatomotor reflexes and the duration of chronic vestibular motor deficits increased. The blood pressure response was observed to depend on injury levels; a moderate injury level produced a hypotensive response while a high injury level produced an immediate brief hypertensive response followed by hypotension. Low injury levels produced no significant macroscopic or microscopic change, but higher injury levels produced cortical contusion and intraparenchymal hemorrhage which, with increasing survival time, evolved into necrotic changes and cavitation underlying the injury site. Also with high levels of injury, axonal injury was found throughout the brain-stem with the greatest concentration of injured axons occurring in the cerebellar peduncles and pontomedullary junction. These data demonstrate that controlled cortical impact in the rat reproduces many of the features observed in other experimental animal models. This model allows independent control of many mechanical loading parameters associated with traumatic brain injury. The controlled cortical impact rat model should be an effective experimental tool to investigators of traumatic brain injury.

Keywords: Brain injury; Brain impact; Cortical contusion; (Rat)

Links

DOI: 10.1016/0165-0270(91)90104-8

PubMed: 1787745

WoS: A1991GT30600007

History

Received: 1991-02-05

Revised: 1991-07-19

Accepted: 1991-08-19

Cited Works (9)

Year	Entry
1982	Anderson TE. A controlled pneumatic technique for experimental spinal cord contusion. J Neurosci Meth. 1982;6(4):327-333.
1974	Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness: correlation of experimental and clinical observations of blunt head injuries. Brain. December 1974;97(4):633-654.
1988	Lighthall JW. Controlled cortical impact: a new experimental brain injury model. J Neurotrauma. 1988;5(1):1-15.
1988	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(3):187-208.
1954	Gurdjian ES, Lissner HR, Webster JE, Latimer FR, Haddad BF. Studies on experimental concussion: relation of physiologic effect to time duration of intracranial pressure increase at impact. Neurology. September 1954;4(9):674-681.
1983	Povlishock JT, Becker DP, Cheng CLY, Vaughan GW. Axonal change in minor head injury. J Neuropathol & Exp Neurol. 1983;42(3):225-242.
1941	Denny-Brown D, Russell WR. Experimental cerebral concussion. Brain. September 1941;64(2-3):93-164.
1987	Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ, Marmarou A, Young HF, Hayes RL. A fluid percussion model of experimental brain injury in the rat. J Neurosurg. July 1987;67(1):110-119.
1981	Feeney DM, Boyeson MG, Linn RT, Murray HM, Dail WG. Responses to cortical injury, I: methodology and local effects of contusions in the rat. Brain Res. April 27, 1981;211(1):67-77.

Cited By (42)

Year	Entry
2005	Smyth A, Gilchrist MD, O’Connor WT. A selective depolarisation-induced increase in excitatory amino acid neurotransmitter release in rat medial prefrontal cortex using a microdialysis model of traumatic brain injury. In: Gilchrist MD, ed. IUTAM Symposium on Impact Biomechanics: From Fundamental Insights to Applications. Dordrecht, The Netherlands: Springer; 2005:393-404. Solid Mechanics and Its Applications; vol 124.
2015	Melvin JW, Yoganandan N. Biomechanics of brain injury: a historical perspective. In: Yoganandan N, Nahum AM, Melvin JW, eds. Accidental Injury: Biomechanics and Prevention. 3rd ed. New York: Springer; 2015:221-245.
2011	Lamy M, Baumgartner D, Yoganandan N, Willinger R. Mild traumatic brain injury in the rat: three‐dimensional finite element model using experimental data. In: Proceedings of the 2011 International IRCOBI Conference on the Biomechanics of Injury. September 14-16, 2011; Krakow, Poland.23-35.
2013	Lamy M, Baumgartner D, Davidsson J, Willinger R. Traumatic brain injury investigation using FE modeling of the rat and experimental high amplitude rotations in the sagittal plane. In: Proceedings of the 2013 International IRCOBI Conference on the Biomechanics of Injury. September 11-13, 2013; Gothenburg, Sweden.456-469.
2016	Dutschke JK, Anderson RWG, Sandoz B, Finnie JW, Manavis J, Nishimoto T, Morris TC, Wells AJ, Turner R, Vink R. A biomechanical model of traumatic contusional injury produced by controlled cerebrocortical indentation in sheep. In: Proceedings of the 2016 International IRCOBI Conference on the Biomechanics of Injury. September 14-16, 2016; Malaga, Spain.354-368.
2006	Mao H, Zhang L, Yang KH, King AI. Application of a finite element model of the brain to study traumatic brain injury mechanisms in the rat. Stapp Car Crash J. 2006;50:583-600. SAE 2006-22-0022.
2012	Viano DC, Hamberger A, Bolouri H, Säljö A. Evaluation of three animal models for concussion and serious brain injury. Ann Biomed Eng. January 2012;40(1):213-226.
1997	Smith DH, Chen X-H, Xu B-N, McIntosh TK, Gennarelli TA, Meaney DF. Characterization of diffuse axonal pathology and selective hippocampal damage following inertial brain trauma in the pig. J Neuropathol & Exp Neurol. July 1997;56(7):822-834.
1996	Adelson PD, Robichaud P, Hamilton RL, Kochanek PM. A model of diffuse traumatic brain injury in the immature rat. J Neurosurg. November 1996;85(5):877-884.
1994	Gennarelli TA. Animate models of human head injury. J Neurotrauma. August 1994;11(4):357-368.
1994	Meaney DF, Ross DT, Winkelstein BA, Brasko J, Goldstein D, Bilston LB, Thibault LE, Gennarelli TA. Modification of the cortical impact model to produce axonal injury in the rat cerebral cortex. J Neurotrauma. October 1994;11(5):599-612.
1995	Smith DH, Soares HD, Pierce JS, Perlman KG, Saatman KE, Meaney DF, Dixon CE, McIntosh TK. A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects. J Neurotrauma. April 1995;12(2):169-178.
1995	Meaney DF, Smith DH, Shreiber DI, Bain AC, Miller RT, Ross DT, Gennarelli TA. Biomechanical analysis of experimental diffuse axonal injury. J Neurotrauma. November 1995;12(4):689-694.
2003	Geddes DM, Cargill RS II, LaPlaca MC. Mechanical stretch to neurons results in a strain rate and magnitude-dependent increase in plasma membrane permeability. J Neurotrauma. October 2003;20(10):1039-1049.
2002	Shaw NA. The neurophysiology of concussion. Prog Neurobiol. July 2002;67(4):281-344.
1999	Viano DC, Lovsund P. Biomechanics of brain and spinal-cord injury: analysis of neuropathologic and neurophysiology experiments. J Crash Prev Injury Control. 1999;1(1):35-43.
2015	Addington C. Modulating Chemokine Receptor Expression in Neural Stem Cell Transplants to Promote Migration After Traumatic Brain Injury [PhD thesis]. Arizona State University; December 2015.
2016	Dutta D. Novel Protein Delivery Platforms to Modulate SDF-1α/CXCR4 Signaling in the Adult Cortex [PhD thesis]. Arizona State University; August 2016.
2008	Kilinc D. Mechanisms and Prevention of Axonal Damage in Response to Mechanical Trauma to Cultured Neurons [PhD thesis]. Drexel University; March 2008.
2014	Dastgheyb RM. Mechanisms of Axonal Pathology in the Context of Traumatic Brain Injury [PhD thesis]. Drexel University; November 2014.
2002	Geddes DM. Selective Vulnerability of Hippocampal Vs. Cortical Neurons to Mechanically Induced Increases in Plasma Membrane Permeability [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; February 2002.
2002	Tate MC. The Development of Extracellular Matrix Based Neural Stem Cell Transplants for Treatment of Traumatic Brain Injury [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2002.
2006	Tate CC. The Role of Extracellular Matrix Proteins in Traumatic Brain Injury and Cell Transplantation [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2006.
2007	Irons HR. Bone Marrow-Derived Mesenchymal Stem Cells as an Alternate Donor Cell Source for Transplantation in Tissue-Engineered Constructs After Traumatic Brain Injury [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2007.
2007	Stabenfeldt SE. Bioactive Thermoresponsive Hydrogels for Neural Tissue Engineering [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; December 2007.
2008	Lessing MC. The Acute Cellular and Behavioral Response to Mechanical Neuronal Injury [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; December 2008.
2011	Wester B. Development and Characterization of Mechanically Actuated Microtweezers for Use in a Single-Cell Neural Injury Model [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2011.
2020	Hogan SR. Utilization of Mass Spectrometric Techniques to Identify Novel Lipid Biomarkers of Traumatic Brain Injury and Other Practical Applications [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2020.
2013	Carlson SW. Evaluation of Insulin-Like Growth Factor-1 as a Therapeutic Approach for the Treatment of Traumatic Brain Injury [PhD thesis]. University of Kentucky; 2013.
2019	Meier SE. Pathological Tau as a Cause, and Consequence, of Cellular Dysfunction [PhD thesis]. University of Kentucky; 2019.
2019	Cournoyer J. Head Impact Severity Associated With Loss of Consciousness and Impact Seizures in Sport-Related Concussions [PhD thesis]. University of Ottawa; 2019.
1998	Bain AC. In Vivo Mechanical Thresholds for Morphological and Functional Axonal Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 1998.
1998	Shreiber DI. Experimental and Computational Modeling of Traumatic Brain Injury: In Vivo Thresholds for Mechanical Disruption of the Blood-Brain Barrier [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 1998.
2005	DeRidder MN. The Role of Cell Kinematics and the N-Methyl D-Aspartate Receptor in Apoptosis and Necrosis in the in Vitro Hippocampus Following Mechanical Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2005.
2010	Spaethling JM. Signaling Leading to Calcium-Permeable AMPA Receptors and Their Role in Neuronal Loss Following Mechanical Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2010.
2014	Chen Y. Astrocyte Signaling in Traumatic Brain Injury [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2014.
2010	Mathur V. Computational Modeling of Controlled Cortical Impact in a Mouse [Master's thesis]. University of Utah; December 2010.
2009	Mao H. Computational Analysis of in Vivo Brain Trauma [PhD thesis]. Detroit, MI: Wayne State University; August 2009.
2011	Kumaran S. Subacute Effect of Olfactory Mucosal Stem Cells in the Treatment of Traumatic Brain Injury [Master's thesis]. Detroit, MI: Wayne State University; December 2011.
2015	Li Y. An Investigation of the Relationship Between Axonal Injury, Biomarker Expression and Mechanical Response in a Rodent Head Impact Acceleration Model [PhD thesis]. Detroit, MI: Wayne State University; 2015.
2020	Zhou R. Development of Rat Head Finite Element Model and Tissue Level Biomechanical Threshold for Traumatic Axonal Injury [PhD thesis]. Detroit, MI: Wayne State University; May 2020.
2022	Kamal SR. Monitoring HDAC Class Ila Activity in the Rat Brain After Traumatic Brain Injury (TBI) Using Noninvasive Pet Imaging With [¹⁸F]TFAHA [PhD thesis]. Detroit, MI: Wayne State University; May 2022.