title: Towards clinical management of traumatic brain injury: a review of models and mechanisms from a biomechanical perspective.
abstract: Traumatic brain injury (TBI) is a major worldwide healthcare problem. Despite promising outcomes from many preclinical studies, the failure of several clinical studies to identify effective therapeutic and pharmacological approaches for TBI suggests that methods to improve the translational potential of preclinical studies are highly desirable. Rodent models of TBI are increasingly in demand for preclinical research, particularly for closed head injury (CHI), which mimics the most common type of TBI observed clinically. Although seemingly simple to establish, CHI models are particularly prone to experimental variability. Promisingly, bioengineering-oriented research has advanced our understanding of the nature of the mechanical forces and resulting head and brain motion during TBI. However, many neuroscience-oriented laboratories lack guidance with respect to fundamental biomechanical principles of TBI. Here, we review key historical and current literature that is relevant to the investigation of TBI from clinical, physiological and biomechanical perspectives, and comment on how the current challenges associated with rodent TBI models, particularly those involving CHI, could be improved.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.
authors.forename: Dhananjay R
authors.initials: DR
authors.lastname: Namjoshi
authors.forename: Craig
authors.initials: C
authors.lastname: Good
authors.forename: Wai Hang
authors.initials: WH
authors.lastname: Cheng
authors.forename: William
authors.initials: W
authors.lastname: Panenka
authors.forename: Darrin
authors.initials: D
authors.lastname: Richards
authors.forename: Peter A
authors.initials: PA
authors.lastname: Cripton
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Wellington
mesh_terms: D001696:Biomechanical Phenomena; D001930:Brain Injuries / Q000628:therapy*; D006801:Humans; D008954:Models, Biological
references.citation: Cent Nerv Syst Trauma. 1985 Winter;2(4):285-98
references.pmid: 3836013
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12705-10
references.pmid: 21765001
references.citation: Neuroscience. 2003;118(4):949-55
references.pmid: 12732240
references.citation: N Engl J Med. 1997 Feb 20;336(8):540-6
references.pmid: 9023090
references.citation: J Neurol Sci. 1991 Jul;103 Suppl:S15-8
references.pmid: 1940960
references.citation: Exp Brain Res. 2003 Mar;149(2):195-9
references.pmid: 12610687
references.citation: J Neurotrauma. 2009 Nov;26(11):1921-8
references.pmid: 19929217
references.citation: Dialogues Clin Neurosci. 2011;13(3):287-300
references.pmid: 22033563
references.citation: Int J Stroke. 2012 Jul;7(5):440-2
references.pmid: 22712743
references.citation: J Vis Exp. 2011 Aug 22;(54):
references.pmid: 21876530
references.citation: MMWR Morb Mortal Wkly Rep. 2007 Jul 27;56(29):733-7
references.pmid: 17657206
references.citation: PLoS One. 2011;6(7):e22899
references.pmid: 21799943
references.citation: J Neurotrauma. 2006 Aug;23(8):1241-53
references.pmid: 16928182
references.citation: Brain Inj. 2009 Jun;23(6):548-58
references.pmid: 19484628
references.citation: Neurology. 2013 Jun 11;80(24):2250-7
references.pmid: 23508730
references.citation: J Neuropathol Exp Neurol. 2011 Jul;70(7):551-67
references.pmid: 21666502
references.citation: Brain Inj. 2012;26(13-14):1523-48
references.pmid: 23163248
references.citation: Nat Rev Neurosci. 2002 Jul;3(7):574-9
references.pmid: 12094213
references.citation: Ann Surg. 2010 Dec;252(6):959-65
references.pmid: 21107105
references.citation: Exp Transl Stroke Med. 2012 Feb 02;4:1
references.pmid: 22300472
references.citation: Neurosurgery. 2001 Oct;49(4):864-71
references.pmid: 11564247
references.citation: Acta Neurochir (Wien). 1976;34(1-4):45-55
references.pmid: 961490
references.citation: J Cereb Blood Flow Metab. 2006 Jun;26(6):771-6
references.pmid: 16306933
references.citation: Ann Emerg Med. 2007 Apr;49(4):391-402, 402.e1-2
references.pmid: 17011666
references.citation: Acta Neurobiol Exp (Wars). 2011;71(1):36-45
references.pmid: 21499325
references.citation: J Biomech Eng. 2004 Apr;126(2):226-36
references.pmid: 15179853
references.citation: J Neurotrauma. 2008 Apr;25(4):324-33
references.pmid: 18373482
references.citation: J Trauma. 1966 Sep;6(5):600-4
references.pmid: 5928630
references.citation: J Neurosci Methods. 2007 Mar 15;160(2):187-96
references.pmid: 17049995
references.citation: Ann Biomed Eng. 2011 Aug;39(8):2130-40
references.pmid: 21553135
references.citation: J Neurotrauma. 2006 Sep;23(9):1304-19
references.pmid: 16958583
references.citation: J Pharmacol Exp Ther. 2001 Jan;296(1):57-63
references.pmid: 11123362
references.citation: Neurocrit Care. 2006;5(1):71-8
references.pmid: 16960300
references.citation: J Neurosurg Pediatr. 2012 Dec;10(6):490-7
references.pmid: 23030382
references.citation: Nat Rev Neurol. 2013 Apr;9(4):211-21
references.pmid: 23458973
references.citation: J Neuropsychiatry Clin Neurosci. 2006 Spring;18(2):141-5
references.pmid: 16720789
references.citation: Ann Biomed Eng. 2013 May;41(5):873-82
references.pmid: 23299827
references.citation: J Neurotrauma. 1994 Dec;11(6):723-32
references.pmid: 7723071
references.citation: J Trauma. 1982 Aug;22(8):680-6
references.pmid: 7108984
references.citation: Nat Protoc. 2009;4(9):1328-37
references.pmid: 19713954
references.citation: Pharmacol Ther. 2011 May;130(2):106-13
references.pmid: 21256863
references.citation: Neurosurgery. 2009 Jun;64(6):1162-73; discussion 1173
references.pmid: 19487897
references.citation: J Trauma Acute Care Surg. 2012 Oct;73(4):895-901
references.pmid: 22836001
references.citation: J Neurotrauma. 2002 Mar;19(3):293-301
references.pmid: 11939497
references.citation: Lancet Neurol. 2011 Feb;10(2):131-9
references.pmid: 21169065
references.citation: Prog Brain Res. 2007;161:13-26
references.pmid: 17618967
references.citation: Lancet. 1974 Jul 13;2(7872):81-4
references.pmid: 4136544
references.citation: J Neurotrauma. 1988;5(2):91-104
references.pmid: 3225860
references.citation: J Neurotrauma. 1992 Winter;9(4):311-22
references.pmid: 1291691
references.citation: Childs Nerv Syst. 2012 Dec;28(12):2033-40
references.pmid: 22832790
references.citation: Lab Invest. 1996 Feb;74(2):315-42
references.pmid: 8780153
references.citation: J Trauma. 2009 Feb;66(2):309-15
references.pmid: 19204502
references.citation: JAMA. 2012 Nov 21;308(19):1993-2000
references.pmid: 23168823
references.citation: J Neurotrauma. 2011 Sep;28(9):1767-82
references.pmid: 21895482
references.citation: Nat Rev Neurol. 2013 Apr;9(4):186-7
references.pmid: 23478463
references.citation: Lancet Neurol. 2008 Aug;7(8):728-41
references.pmid: 18635021
references.citation: J Head Trauma Rehabil. 2010 Sep-Oct;25(5):357-61
references.pmid: 20220529
references.citation: Acad Emerg Med. 2004 Aug;11(8):809-19
references.pmid: 15289185
references.citation: J Neurosurg. 1991 Nov;75(5):731-9
references.pmid: 1919695
references.citation: J Neurosurg. 1981 Nov;55(5):708-17
references.pmid: 7310492
references.citation: Annu Proc Assoc Adv Automot Med. 2007;51:343-61
references.pmid: 18184501
references.citation: J Trauma. 2001 Sep;51(3):481-9
references.pmid: 11535895
references.citation: J Neuropathol Exp Neurol. 1997 Jul;56(7):822-34
references.pmid: 9210879
references.citation: J Neurosurg. 2010 May;112(5):1150-3
references.pmid: 19645536
references.citation: J Int Med Res. 1981;9(3):215-21
references.pmid: 7016627
references.citation: Clin Sports Med. 2011 Jan;30(1):19-31, vii
references.pmid: 21074079
references.citation: Chin J Traumatol. 2003 Oct;6(5):302-4
references.pmid: 14514369
references.citation: Ann Biomed Eng. 2012 Jan;40(1):1-13
references.pmid: 22012081
references.citation: Life Sci. 1992;51(3):185-93
references.pmid: 1614284
references.citation: J Neurotrauma. 2011 Jan;28(1):57-70
references.pmid: 21047148
references.citation: NeuroRehabilitation. 2007;22(5):341-53
references.pmid: 18162698
references.citation: Ann Neurol. 1982 Dec;12(6):564-74
references.pmid: 7159060
references.citation: J Neurosurg. 1986 Dec;65(6):820-4
references.pmid: 3095507
references.citation: Eur J Neurosci. 2005 May;21(10):2876-82
references.pmid: 15926935
references.citation: J Neurosurg. 1994 Feb;80(2):301-13
references.pmid: 8283270
references.citation: J Neurosci Methods. 1991 Oct;39(3):253-62
references.pmid: 1787745
references.citation: Cent Nerv Syst Trauma. 1987;4(2):119-34
references.pmid: 3690695
references.citation: J Neurotrauma. 2002 Aug;19(8):939-51
references.pmid: 12225654
references.citation: J Trauma. 2008 May;64(5):1313-9
references.pmid: 18469656
references.citation: J Neurotrauma. 1996 Oct;13(10):557-68
references.pmid: 8915907
references.citation: Front Neurol. 2011 Jun 17;2:41
references.pmid: 21747777
references.citation: J Neurotrauma. 2005 Sep;22(9):1003-10
references.pmid: 16156715
references.citation: Nihon Ika Daigaku Zasshi. 1997 Apr;64(2):172-5
references.pmid: 9128055
references.citation: Clin Anat. 2011 Apr;24(3):294-308
references.pmid: 21433079
references.citation: Neurosurgery. 2003 Oct;53(4):799-812; discussion 812-4
references.pmid: 14519212
references.citation: Exp Neurol. 2011 Dec;232(2):280-9
references.pmid: 21946269
references.citation: Neurosurgery. 1990 Sep;27(3):422-8
references.pmid: 2234336
references.citation: J Neurosurg. 1985 Jun;62(6):882-7
references.pmid: 3998840
references.citation: J Head Trauma Rehabil. 2006 Sep-Oct;21(5):375-8
references.pmid: 16983222
references.citation: Neurosurgery. 2008 Apr;62(4):789-98; discussion 798
references.pmid: 18496184
references.citation: J Neurotrauma. 2012 Nov 20;29(17):2606-12
references.pmid: 23031217
references.citation: J Neurotrauma. 1997 Nov;14(11):851-62
references.pmid: 9421456
references.citation: J Emerg Med. 1993;11 Suppl 1:5-11
references.pmid: 8445204
references.citation: Neurology. 1955 Nov;5(11):798-800
references.pmid: 13265993
references.citation: N Engl J Med. 2012 Dec 27;367(26):2471-81
references.pmid: 23234472
references.citation: Acta Neurochir (Wien). 2006 Mar;148(3):255-68; discussion 268
references.pmid: 16311842
references.citation: J Neurotrauma. 2001 Mar;18(3):247-57
references.pmid: 11284546
references.citation: JAMA. 2004 Mar 17;291(11):1350-7
references.pmid: 15026402
references.citation: J Trauma. 2008 Apr;64(4):854-62
references.pmid: 18404048
references.citation: Surg Neurol. 2003 May;59(5):381-5
references.pmid: 12765810
references.citation: J Neurotrauma. 2009 Dec;26(12):2233-43
references.pmid: 19929375
references.citation: Acta Neuropathol Suppl. 1981;7:23-5
references.pmid: 6939241
references.citation: Neurosurgery. 2002 Sep;51(3):628-37; discussion 637-8
references.pmid: 12188940
references.citation: Br J Pharmacol. 2011 Oct;164(4):1207-29
references.pmid: 21175576
references.citation: Crit Care Nurs Q. 2000 Nov;23(3):1-13
references.pmid: 11852934
references.citation: Clin Sports Med. 2011 Jan;30(1):179-88, xi
references.pmid: 21074091
references.citation: Mt Sinai J Med. 2009 Apr;76(2):111-8
references.pmid: 19306373
references.citation: Ann Biomed Eng. 2012 Jan;40(1):213-26
references.pmid: 22012080
references.citation: J Neurosci Methods. 2012 Jan 15;203(1):41-9
references.pmid: 21930157
references.citation: Crit Care. 2008;12(2):R61
references.pmid: 18447940
references.citation: Arch Neurol. 1994 Jul;51(7):653-60
references.pmid: 8018037
references.citation: Nat Rev Neurol. 2013 Apr;9(4):222-30
references.pmid: 23478462
references.citation: J Neurotrauma. 2010 Jan;27(1):21-33
references.pmid: 19751098
references.citation: J Neurotrauma. 2002 Apr;19(4):427-38
references.pmid: 11990349
references.citation: Brain Inj. 2013;27(3):318-24
references.pmid: 23438351
references.citation: Dev Neurosci. 2006;28(4-5):380-7
references.pmid: 16943661
references.citation: Aust Vet J. 2001 Sep;79(9):628-33
references.pmid: 11702936
references.citation: J Neurosurg. 2000 Aug;93(2):315-22
references.pmid: 10930019
references.citation: J Rehabil Med. 2004 Feb;(43 Suppl):28-60
references.pmid: 15083870
references.citation: J Neurotrauma. 2001 Mar;18(3):259-73
references.pmid: 11284547
references.citation: Brain Res. 1981 Apr 27;211(1):67-77
references.pmid: 7225844
references.citation: J Neurosurg. 2001 Nov;95(5):859-70
references.pmid: 11702878
references.citation: J Neurosurg. 1994 Feb;80(2):291-300
references.pmid: 8283269
references.citation: Brain Inj. 1987 Jul-Sep;1(1):73-91
references.pmid: 3454675
references.citation: Stapp Car Crash J. 2001 Nov;45:337-68
references.pmid: 17458753
references.citation: Lancet Neurol. 2013 Jun;12(6):546-53
references.pmid: 23664370
references.citation: J Neurotrauma. 2006 Jul;23(7):1083-93
references.pmid: 16866621
references.citation: Lancet Neurol. 2013 Jan;12(1):53-64
references.pmid: 23177532
references.citation: Surg Gynecol Obstet. 1955 Dec;101(6):680-90
references.pmid: 13274275
references.citation: J Neurosurg. 2009 Jun;110(6):1256-64
references.pmid: 19249933
references.citation: J Neurotrauma. 2013 Jan 15;30(2):102-18
references.pmid: 22992118
references.citation: N Engl J Med. 2012 Mar 1;366(9):819-26
references.pmid: 22375973
references.citation: J Neurotrauma. 2007 Apr;24(4):657-73
references.pmid: 17439349
references.citation: Surg Gynecol Obstet. 1975 Jun;140(6):845-50
references.pmid: 1093271
references.citation: Nat Rev Neurosci. 2013 Feb;14(2):128-42
references.pmid: 23329160
references.citation: J Neurotrauma. 1997 Nov;14(11):863-73
references.pmid: 9421457
references.citation: Nat Rev Neurol. 2013 Apr;9(4):231-6
references.pmid: 23443846
references.citation: J Neurotrauma. 2003 Feb;20(2):169-78
references.pmid: 12675970
references.citation: Surg Gynecol Obstet. 1961 Aug;113:185-90
references.pmid: 13709837
references.citation: J Neurol Neurosurg Psychiatry. 2009 May;80(5):552-7
references.pmid: 19060022
references.citation: J Crit Care. 2007 Sep;22(3):229-35
references.pmid: 17869973
references.citation: Surg Gynecol Obstet. 1960 Sep;111:329-38
references.pmid: 14417481
references.citation: J Rehabil Med. 2004 Feb;(43 Suppl):113-25
references.pmid: 15083875
references.citation: J Neurotrauma. 2005 Jun;22(6):623-8
references.pmid: 15941372
references.citation: Neuroscience. 1997 Oct;80(4):1255-62
references.pmid: 9284075
references.citation: Injury. 1989 Jan;20(1):16-21
references.pmid: 2592058
references.citation: J Head Trauma Rehabil. 2008 Jan-Feb;23(1):52-63
references.pmid: 18219235
references.citation: J Neurotrauma. 1996 Jan;13(1):25-34
references.pmid: 8714860
references.citation: J Neurotrauma. 2005 Jan;22(1):42-75
references.pmid: 15665602
references.citation: J Physiol. 1940 Dec 20;99(1):153
references.pmid: 16995229
references.citation: Neurosci Lett. 1978 Jun;8(3):255-8
references.pmid: 19605168
references.citation: Br J Anaesth. 2007 Jul;99(1):4-9
references.pmid: 17573392
references.citation: J Biomed Biotechnol. 2011;2011:797383
references.pmid: 21331361
references.citation: J Neurotrauma. 1995 Apr;12(2):169-78
references.pmid: 7629863
references.citation: J Neurotrauma. 2011 Sep;28(9):1747-55
references.pmid: 21740133
references.citation: N Engl J Med. 2008 Jan 31;358(5):453-63
references.pmid: 18234750
references.citation: Dis Model Mech. 2013 Nov;6(6):1307-15
references.pmid: 24046353
references.citation: J Neurotrauma. 2009 Aug;26(8):1307-14
references.pmid: 19317611
references.citation: NeuroRx. 2005 Jul;2(3):410-22
references.pmid: 16389305
references.citation: Spine (Phila Pa 1976). 2009 Jul 15;34(16):1650-7
references.pmid: 19770607
references.citation: Cent Nerv Syst Trauma. 1985 Summer;2(2):75-83
references.pmid: 3938345
references.citation: Am J Phys Med Rehabil. 2004 Jun;83(6):401-20
references.pmid: 15166683
references.citation: Clin Neurol Neurosurg. 2006 Sep;108(6):539-42
references.pmid: 16226371
references.citation: J Neurotrauma. 1989;6(2):83-97
references.pmid: 2671392
references.citation: Sci Transl Med. 2012 May 16;4(134):134ra60
references.pmid: 22593173
references.citation: J Athl Train. 2001 Sep;36(3):228-235
references.pmid: 12937489
references.citation: J Neurosurg. 1996 Jul;85(1):82-9
references.pmid: 8683286
references.citation: N Engl J Med. 2011 Apr 21;364(16):1493-502
references.pmid: 21434843
references.citation: Chin J Traumatol. 2005 Feb;8(1):27-32
references.pmid: 15676086
references.citation: J Neurosurg. 2001 Jan;94(1):50-4
references.pmid: 11147897
references.citation: Neuroscience. 1989;28(1):233-44
references.pmid: 2761692
references.citation: J Neurotrauma. 1995 Aug;12(4):621-5
references.pmid: 8683613
references.citation: Surg Gynecol Obstet. 1958 Nov;107(5):593-601
references.pmid: 13592659
references.citation: J Trauma. 2006 Mar;60(3):558-65
references.pmid: 16531854