TABLE 2.

Effects of choline-containing phospholipids (CCPLs) in different elements of neurovascular unit (NVU) evaluated in different in vitro and in vivo models.

In vitro or in vivo model	Evidence	References
Main results for neurons
Neuronal cell cultures	Phosphatidylcholine could play a signalling role during neuronal differentiation	Paoletti et al., 2011
Primary cultured neurons treated with Aβ1-42-induced damage	Phosphatidylcholine prevented neuronal death	Ko et al., 2016
Aged mice	Phosphatidylcholine had no effect on hippocampal dendritic spine density compared to control, but improved learning and memory	Muma and Rowell, 1988
Wistar rats with ischemia/reperfusion (I/R)-induced insult	Phosphatidylcholine has a possible neuroprotective effect partly through its antioxidant action	Aabdallah and Eid, 2004
Aging rats	Dietary CDP-choline supplementation can protect impairment in hippocampal-dependent long-term memory.	Teather and Wurtman, 2003
Long Evans rats	CDP-choline significant increases in neurite length, branch points and total area occupied by the neurons were observed	Rema et al., 2008
Human dopaminergic SH-SY5Y neuroblastoma cells	CDP-choline reduces the cytotoxic effect of 6-hydroxydopamine (6-OHDA)	Barrachina et al., 2003
Rats	α-GPC increase acetylcholine level, facilitates learning and memory, improves brain transduction mechanisms	Traini et al., 2013
Rats	α-GPC increase dopamine levels, whereas dopamine transporter expression was stimulated by both CDP and α-GPC in brain areas	Tayebati et al., 2013
Spontaneously hypertensive rats (SHR) as a model of cerebrovascular disease	α-GPC prevent neuronal alterations	Tayebati et al., 2009, 2015; Tomassoni et al., 2006, 2012
Pilocarpine-induced seizure in rat	α-GPC, starting 3 weeks after seizure improved cognitive	Lee et al., 2018
Rat model of dual stress	α-GPC countered the increase of stress hormones, reduced hearing loss, and prevented neuronal injury	Jeong Yu et al., 2022
Main results for astrocytes
Primary astrocyte cultures	Active role played by CCPLs., particularly a-GPC throughout differentiation processes	Bramanti et al., 2008a,b, 2012; Grasso et al., 2014
Spontaneously hypertensive rats (SHR) as a model of cerebrovascular disease	α-GPC reduced astrogliosis and the expression of aquaporin-4	Tayebati et al., 2009, 2015; Tomassoni et al., 2006
Rat with middle cerebral artery occlusion as a model of stroke	CDP-choline reduced glial fibrillary acidic protein levels in the peri-infarct area of the ischemic stroke	Gutiérrez-Fernández et al., 2012a,b
Main results for microglia
Rat model of on oxaliplatin-induced neuropathy	CDP-choline administration ameliorated microglial activation	Kim S. T. et al., 2015
pilocarpine-induced epilepsy in rat	CDP-Choline treatment enhanced seizure-induced neuronal death and microglial activation	Kim J. H. et al., 2015
Rat with docetaxel-induced peripheral neurotoxicity	CDP choline significantly decreased microglial activation and M1 polarization in rat hippocampus	Kim S. T. et al., 2018
Senescence-accelerated mouse prone 8 (SAMP-8)	α-GPC protect the brain by reducing TTR deposition and preventing neuroinflammation.	Matsubara et al., 2018
Spontaneously hypertensive rats (SHR) as a model of cerebrovascular disease	α-GPC induce a reduction of microglial activation	Tayebati et al., 2015
Main results for endothelial cells and pericytes
Human umbilical vein endothelial cells (HUVECs) under hypoxia/aglycemia conditions	CDP-choline decreased the permeability with an increased expression of the tight junction proteins	Ma et al., 2013
Rat with middle cerebral artery occlusion as a model of stroke	CDP-choline increased cell proliferation, and vasculogenesis	Gutiérrez-Fernández et al., 2012a,b
Spontaneously hypertensive rats (SHR) as a model of cerebrovascular disease	α-GPC affect endothelial markers and vascular adhesion molecules expression ICAM-1, VCAM-1, and PECAM-1	Tayebati et al., 2015