Table 2.

A summary of the protective effect of crocin on cerebral ischemia, ischemic stroke, traumatic brain and spinal cord injury

	Experimental model	Effect	Ref.
Crocin	Mice	Protected I/R injury-induced oxidative and nitrosative damage in cerebral micro vessels by decreasing NO, NOS, MDA, phosphorylation of extracellular signal-regulated kinase 1/2 ERK1/2 phosphorylation and MMP-9, increasing the activities of SOD and GPx and also inhibiting translocation of the GRK2 from the cytosol to the membrane	[30]
	Rat	Prevented ischemic reperfusion injury and cerebral edema by decreasing the levels of MDA and increasing the activity of SOD and GPx in the cortex	[31]
		Prevented the global cerebral IR induced by four-vessel occlusion via modulating oxidative stress indices (TAS, TOS, OSI), HIF-1α, TUNEL-positive cell and caspase-3 in brain	[32]
	Mice	Prevented brain damage after TBI by decraesing pro-inflammatory cytokines	[5]
		Prevented TBI by decreasing microglial activation, several pro-inflammatory cytokines, and cell apoptosis	[33]
	Rat	Protected the BBB damage in aged rats following cerebral ischemia via enhancing NADPH oxidase and blocking the induction of MMP-2 and MMP-9	[34]
		Improved chronic pain caused by SCI by reducing as a main pain and inflammatory mediators.	[6]

Abbreviations: I/ R: ischemia/reperfusion, NO: nitric oxide, NOs: nitric oxide synthase, MDA: malondialdehyde, MMP: matrix metalloproteinases, SOD: superoxide dismutase, ERK1/2: extracellular signal-regulated kinase 1/2, GPx: glutathione peroxidase, TOS: Total Oxidant Status, TOS: total oxidant status, OSI: Oxidative Stress Index, HIF-1: hypoxia-inducible factor 1, TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling, TBI: traumatic brain injury, BBB: blood-brain barrier, NADPH: Nicotinamide adenine dinucleotide phosphate, SCI: spinal cord injury.