TABLE 1.

Administration of HGF and HGF mimetics in animal models of neurological diseases.

Disease application	Methods	Year	Animal model	Outcomes	References
ALS	Continuous intrathecal delivery of rhHGF in transgenic rats (SOD1-G93A)	2007	Rat	Inhibition of caspase-3 and -9 induced apoptosis in motor neurons and XIAP levels enhancement; enhancement of EAAT2 protein in astrocytes	Ishigaki et al., 2007
	Continuous administration of rhHGF intrathecally after a cervical spinal cord injury	2019	Marmoset	Functional recovery promotion	Aoki et al., 2019
	Intraperitoneal administration of K1K1 in transgenic rats (SOD1-G93A)	2020	Mouse	Rescue of motor neurons from death in spinal-neuron astrocyte co-cultures and in the lumbar spinal cord of transgenic mice; transient amelioration of the muscle force impairment	Vallarola et al., 2020
AD	Intraperitoneal injection of the HGF mimetic dihexa in the scopolamine amnesia and aged-related models	2013	Rat	Antidementia potential; dendritic spinogenesis augmentation in the hippocampus	McCoy et al., 2013
SCI	Intrathecal rhHGF infusion during the acute phase of cervical SCI	2011	Marmoset	Functional recovery; cortical fibers and myelinated area protection	Kitamura et al., 2011
	Engineered HGF with a collagen binding domain (CBD-HGF) and photo-cross-linkable gelatin-gelatin-furfurylamine	2018	Mouse	Axonal regeneration promotion; motor recovery; neutrophil and macrophage reduction	Yamane et al., 2018
Cerebral ischemia	Sponge soaked with rhHGF in tMCAO models	2010	Rat	Modulation of autophagy and apoptosis	Shang et al., 2010
	Acute intra-striatal injection of HGF in a stroke model	2011	Mouse	Proliferation of neural progenitor cells and protection from caspase-induced death; reduction of post-ischemic functional deficits; diminution of the BBB permeability by MMP inactivation	Doeppner et al., 2011
	Gelatin hydrogel microspheres containing HGF in MCAO stroke model	2012	Mouse	Increased number of new neurons migrating from the SVZ toward the injured striatum in a stroke model in adult mice	Nakaguchi et al., 2012
	BB3 administration in tMCAO or pMCAO models for 14 days	2015	Rats	Long-term neurologic function improvement; little effect on cerebral infarct size reduction	Chaparro et al., 2015

AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; BBB, blood brain barrier; EAAT2, excitatory amino acids transporter 2; MCAO, middle cerebral artery occlusion; MMP, matrix metallo-proteinases; PD, Parkinson’s disease; pMCAO, permanent middle cerebral artery occlusion; rhHGF, recombinant human hepatocyte growth factor; SCI, spinal cord injury; SVZ, sub-ventricular zone; tMCAO, transient middle cerebral artery occlusion; XIAP, X-linked inhibitor of apoptosis protein.