Table 1.

Studies of the influence of specific genes on recovery in mouse models of traumatic brain injury, spinal cord injury, and stroke.

Biological Process	TBI Model	Gene	Functional assessment	Cellular mechanism	Reference
Cell death and inflammation	Lateral fluid percussion	BDNF Val66Met v wild type	Administration of BDNF to Val66Met carriers improved motor and cognitive function	↓apoptosis, inflammation, and gliosis in wt mice	85
	CCI	Ccr2	Better locomotor recovery in -/- mice	↓macrophage infiltration ↑neuronal survival in CA1-CA3 of hippocampus in -/- mice	86
	CCI	Il13	sensorimotor function enhanced by IL13 administration	↓pro-inflammatory macrophage infiltration, ↑phagocytosis of dead neurons	87
Neurogenesis	CCI	Epo	Epo administration improved sensorimotor function and spatial learning	↑neurogenesis in mice given Epo	88
	CCI	Gdf5	Improved cognitive function and decreased behavioral dysfunction	↑neurogenesis in mice given Gdf5	89
	Cryogenic lesion, CCI	Hrh1 postsynaptic and Hrh3 presynaptic histamine receptors	Improved sensorimotor function in Hrh3 -/- mice or mice given H3R antagonist	↑neurogenesis and recovery in H3-/- mice or mice given H3 antagonist ↓neurogenesis in Hrh1-/- better neuronal differentiation in wt mice	90
Axonal sprouting	SCI	Ngr1	Histological assessment of axonal regeneration	NogoA -/- shows greater regenerating fibers	25
	Unilateral pyramidotomy	Pten-Socs3	Pten-Socs3 deletion improves motor function	Increased sprouting of uninjured axons to denervated cord in KO animals	48
	SCI	Pten	Improved motor function in conditional KO mice	Increased regenerative growth of corticospinal axons	49
	Photothrombotic stroke	Gdf10	GDF10 administration improved and knockdown worsened motor recovery	Increased axonal sprouting in mice given GDF10, with downregulation of PTEN	52
Dendritic spine remodeling	CCI	MMP9	Histologic assessment only	No ↓in spine density or spine shrinkage following TBI in MMP9-/- mice	91
	CCI	Rhoa-Rock1	Rho conditional knockout in postnatal neurons or ROCK chemical inhibition improved motor and cognitive recovery	Rho inhibition reduces pathological spine remodeling and loss post-TBI	92
Myelin regeneration	Contusion/compression SCI	PAR2	Histological assessment of myelination post-injury	Improved myelin resiliency and remyelination in PAR2 -/- mice	93
	CCI	Plat	-/- mice show greater sensorimotor defects and reduced spatial learning and memory, decreased axonal conduction rate	Administration of TPA to -/- mice enhanced white matter structure, increased compensatory neuronal sprouting	94
Revascularization	Cryogenic lesion	Il6	Pathologic assessment of lesion	↓vascularization, poor recovery in IL6 -/- mice	95
General recovery	photothrombotic stroke	Epha4	Motor function recovery enhanced in Epha4 partial knockdown mice and by downstream inhibition of pathway with Rho kinase inhbitor	Not assessed	47
	Photothrombotic stroke, CCI	Ccr5	Enhancement of motor function recovery in stroke and cognitive ability in TBI after shRNA or chemical knockdown of CCR5	Preservation of dendritic spines and new cortical projections to contralateral cortex in stroke	54

CCI controlled cortical impact, SCI spinal cord injury, wt wild type, KO Knockout.