TABLE 1.

Evidence supporting the neuroregenerative properties of classical neuroptrophin use in the context of treatments for CNS disease/injury.

Neurotrophin	Species	Disease model/Injury	Intervention/Treatment	Neuroregenerative effect	References
NGF	Rat	Unilateral lesion to nucleus basalis	Implantation of NGF-secreting fibroblasts	Enhanced NGF-induced axonal growth	Kawaja and Gage, 1991
	Rhesus Monkeys	Unilateral transection of the fornix	Implantation of NGF-secreting fibroblasts	Enhanced sprouting of cholinergic fibers	Kordower et al., 1994
	Rat	Complete crush injuries to the cervical DRG	Intrathecal NGF via osmotic minipumps	Regrowth of unmyelinated DRG fibers, restoration of behavioral sensitivity and stimulus-driven postsynaptic activity	Ramer et al., 2000
	Rat	Immunotoxic lesions to the CBF	Intracerebroventricular NGF via osmotic minipumps	Hypertrophy and enhanced axonal growth in CBF neurons, improved spatial orientation in a water maze	Winkler et al., 2000
BDNF	Rat	Optic nerve transection	Intravitreal BDNF injections	Enhanced local regrowth of RGC axons near the optic disc	Mansour-Robaey et al., 1994
	Mice	Striatal lesion	Intrastriatal infusion of BDNF antisense oligonucleotides via minipumps	Suppressed peri-wound dopaminergic sprouting	Batchelor et al., 2000
	Rat	PCA-induced lesions (forebrain or hippocampus)	BDNF infusions to lesion site via osmotic minipumps	Enhanced sprouting of 5-HT axons at the lesion site (both the forebrain and hippocampus)	Mamounas et al., 2000
	Rat	Complete transection of the thoracic spinal cord	Intrathecal BDNF via osmotic minipumps	Enhanced functional recovery of the hindlimb, modest sprouting of cholinergic fibers within injury cavity	Jakeman et al., 1998
	Rat	Photothrombotic stroke to the parietal cortex	Intravenous BDNF injections	Enhanced functional recovery of motor function, promoted widespread neuronal remodeling	Schäbitz et al., 2004
	Rat	Photothrombotic stroke to the parietal cortex	Intravenous BDNF injections	Enhanced functional recovery of sensorimotor function, neurogenesis (DG) and SVZ progenitor cell migration	Schäbitz et al., 2007
	Rat	MCAO via permanent intraluminal vascular occlusion	Intraventricular injections of CBD-bound BDNF	Enhanced SVZ progenitor cell proliferation, enhanced angiogenesis and improved neurological performance	Guan et al., 2012
	Rat	Endothelin-1-induced MCAO	Intraventricular infusion of BDNF antisense oligonucleotides via minipumps	Attenuated rehabilitation-mediated functional recovery of motor skills	Ploughman et al., 2009
	Mice	Photothrombotic stroke to the motor cortex	TrkB-Fc-embedded hydrogel into stroke cavity	Occluded AMPAkine-mediated and spontaneous functional recovery	Clarkson et al., 2011
NT-3	Mice	N/A	Conditional NT-3 knockout	Impaired NPC differentiation and LTP, deficits in spatial memory	Shimazu et al., 2006
	Rat	Partial bilateral transection of the thoracic spinal cord	Intrathecal NT-3 injection	Enhanced axonal sprouting of transected corticospinal tract	Schnell et al., 1994
	Rat	Partial bilateral crushing of the thoracic spinal cord	Intrathecal NT-3 via osmotic minipumps	Enhanced axonal growth within and outside the lesion site	Bradbury et al., 1999
		Focal hypoxic-ischemic brain injury	Implantation of NT-3-overexpressing NSCs	Promoted NSC differentiation into neurons, dampened glial scarring	Park et al., 2006
	Rat	Partial bilateral transection of the thoracic spinal cord	Implantation of NT-3-secreting fibroblasts	Enhanced axonal growth around and distal to lesion site, partial recovery of motor function	Grill et al., 1997

DRG, dorsal root ganglion; CBF, cholinergic basal forebrain; RGC, retinal ganglion cells; PCA, p-chloroamphetamine; DG, dentate gyrus; SVZ, subventricular zone; MCAO, middle cerebral artery occlusion; CBD, collagen binding domain; TrkB-Fc, tropomyosin receptor kinase B-Fc; NPC, neural progenitor cell; LTP, long term potentiation; NSC, neural stem cells.