Table 1.

Animal models using more than one head impact but satisfying few of the desired criteria of a model of human sports-related rmTBI

Animal modela and reference	Subject	Direct hit on intact scalp and skull/craniotomy	Head free to move upon impact	No. impactsb, time between impacts	Accommodates young subjects	Psychiatric (Psy) and/or cognitive (Cog) manifestations	CTE-like tauopathy; other injuries
Marmarou and related weight drop variants
Allen et al. 2002	Adult rat	Yes/yes	No-in stereotax	3 @ 3 daysc	NDd	ND-Cog	ND; cortical damage, necrosis, gliosis
						ND-Psy
DeFord et al. 2002	Adult mouse	Yes/no	No-cushion used	1-4 @ 24 h	ND	Yes - Cog	ND; no overt pathology
						ND-Psy
Creeley et al. 2004	Adult mouse	Yes/no	No-firm mold	1-3 @ 24 h	ND	Yes - Cog	ND; neurodegeneration
						ND-Psy
Namjoshi et al. 2013	Adult mouse	Yes/no	No	2 @ 24 h	ND	Yes - Cog	ND; axonal damage, cortical contusions
						ND-Psy
Controlled cortical impact and variants
Laurer et al. 2001	Adult mouse	Yes/no	No-in stereotax	1-2 @ 24 h	ND	Neither	No; axonal injury
Uryu et al. 2002	Adult Tg mouse	Yes/no	No-in stereotax	1-2 @ 24 h	ND	Yes - Cog	ND; Aβ ↑
						ND-Psy
Conte et al. 2004	Adult Tg mouse	Yes/no	No-in stereotax	1-2 @ 24 h	ND	Yes - Cog	ND; Aβ ↑
						ND-Psy
Longhi et al. 2005	Adult mouse	Yes/no	No-in stereotax	1-2 @ 3,5, or 7 days	ND	Yes - Cog	ND; cytoskeletal, neuronal and axonal damage
						ND-Psy
Yoshiyama et al. 2005	Adult Tg mouse	Yes/no	No-in stereotax	4 or 16 @ 20 min	ND	No-Cog	yes
						ND-Psy
Huh et al. 2007	PND11 rat	Yes/no	No-foam pad	1, 2, or 3 @ 5 min	Yes	Yes - Cog	ND; axonal swelling, degeneration
						ND-Psy
Prins et al. 2010	PND35 rat	Yes/no	No-head against wooden block	1-2 @ 24 h	Yes	Yes - Cog	ND; axonal injury; gliosis
						ND-Psy
Shitaka et al. 2011	Adult mouse	Yes/no	No-in stereotax	1-2 @24 h	ND	Yes - Cog	ND; cytoskeletal and axonal damage, gliosis
						ND-Psy
Mouzon et al. 2012	Adult mouse	Yes/no	No-in stereotax	1 or 5 @ 48 h	ND	Yes - Cog	No; axonal injury
						ND-Psy
Bennett et al. 2012	Adult mouse	Yes/no	No-in stereotax	1-2 @24 h	ND	ND-Cog	ND; DTI deficits; axonal injury
						ND-Psy
Prins et al. 2013	PND35 rat	Yes/no	No-head against wooden block	1-2 @ 24 or 120 h	Yes	Yes-novel object deficits	ND; metabolic depression
Lateral fluid percussion and variants
Kanayama et al. 1996	Adult rats	Yes/yes	No-in stereotax	1 or 7 @ 24 h	ND	Neither	yes
DeRoss et al. 2002	Adult rat	Yes/yes	No-in stereotax	1, 2 or 3 @ ?	ND	Yes - Cog	ND
						ND-Psy

^aSee Xiong et al. (2013) for representative review of animal models of TBI and their nomenclature.

^bMany recent variants of the models under discussion have now administered 2 or 3 injuries and refer to these as mild and repeated. However, these injuries are still much more severe than those seen in athletes who have received hundreds of subconcussive head impacts. For the sake of the present discussion, studies that used 3 or more head impacts were included as satisfying this criterion because they represent a minority. The ‘correct’ number of head impacts for use in animal models is not known (see text for discussion).

^cShading in a cell indicates fulfillment of a criterion of an effective animal model of sports-related head injury.

^dND, not determined; Tg, transgenic; Aβ, amyloid beta; PND, postnatal day; DTI, diffusion tensor imaging.