Table 2.
Model | Animal Treatment | Effects of Vitamin D | Reference |
---|---|---|---|
Hypoxia ischemia (HI) rat model | Hypothermia treatment + NAC (50 mg/kg) + 1,25-(OH)2D3 (0.1 μg/kg/)/daily for 2 weeks |
↑motor skills ↓anxiety ↑spatial learning |
[103] |
Rat model of perinatal asphyxia in 7-day-old pups | 1,25(OH)2D3 (2 μg/kg, i.p., single dose)/30 min after the insult or for 6 consecutive days | ↓brain damage | [98] |
MCAO/R rat model of I/R injury |
1,25(OH)2D3 (1 μg/kg i.p.)/day/8 days before ischemia. DHA (250 mg/mL, from tail vein/30 min before MCAO/R |
↓MDA ↑GSH, SOD activity in cortex and corpus striatum in 1,25(OH)2D3 + DHA group |
[104] |
MCA ligation model in rat | 1,25(OH)2D3, 1 μg/kg/day, i.p., 4 or 8 days | ↓the amount of infarction in the cortex, ↑GDNF levels |
[105] |
MCAO/R model in C57BL6 mice | 1,25(OH)2D3 (100 ng/kg, i.p./day/5 day prior to stroke | ↓infarct volume ↓pro-inflammatory mediators IL-6, IL-1β, IL-23a, TGF-β and NADPH oxidase-2 |
[106] |
Spinal cord I/R injury in rabbit | 1,25(OH)2D3 (0.5 μg/kg, i.p./7 days before I/R) | ↓MDA, myeloperoxidase, xanthine oxidase activities, caspase-3 level, ↑catalase level, histopathological, ultrastructural, and neurological scores |
[107] |
BCAO model in Mongolian gerbils | 1,25(OH)2D3 1 μg/kg, i.p./day/7 days prior to ischemia. | ↓MMP-9 ↓lipid peroxidation ↓superoxide anion production ↑VDR expression |
[108] |
GCI model in rat | 1,25(OH)2D3 (1 μg/kg, i.p.)/30 min, 12 and 24 h after the GCI insult and PD98059 (5 μg, through the tail vein)/30 min prior to the insult | ↓brain edema, ↑neurological function, ↑ERK 1/2 pathway activation, ↓neuronal apoptosis |
[109] |
GCI model in rat |
1,25(OH)2D3 (1 μg/kg, i.p.)/30 min, 12 and 24 h after the GCI insult and PD98059 (5 μg, through the tail vein)/30 min prior to the insult |
↑the spatial learning and memory ↑neurological function ↓brain edema, ↓morphological defects in the CA1 area of the hippocampus ↓apoptosis ↑ VDR expression ↑ERK 1/2 pathway activation—PD98059 reversed the anti-apoptotic effect of 1,25(OH)2D3 |
[110] |
MCAO model in rat | 1,25(OH)2D3, 7 days prior to stroke induction | ↓lesion volume, ischemic neurobehavioral deficits, regulation of the glutamate receptor expression and CYP46A1 genes |
[111] |
MCAO model in rat | 1,25(OH)2D3 i.p., (a single dose of 2 μg/kg, immediately following ischemia) and subchronically (2 μg/kg on 6 consecutive days). | ↓infarct volumes 7 days following reperfusion, ↑NR3A and CREB activity in the hippocampal neurons, protection of the brain from I/R injury through the NR3A-MEK/ERK1/2-CREB pathway |
[112] |
Focal cortical ischemia (photothrombosis model) in rat | Lesioned rats were injected i.p. one hour after injury with either 1 μg 1,25(OH)2D3/kg or 7 μg 17β-estradiol/kg or a combination of both steroids | ↓HSP-27 within the infracted cerebral cortex | [114] |
tMCAO model in rat | Progesterone (8 mg/kg), 1,25(OH)2D3 (1 μg/kg body weight/day) alone or in a combination, 5 min. i.p. prior to reperfusion followed by daily s.c. injections for 6 days. | ↓motor deficits, infarct reduction, ↑BDNF, TrkB and p-ERK1/2 expression, ↓apoptosis (↑Bcl-2, ↓caspase-3) ↓IL-6 and p-NF-κB ↑HO-1 |
[100] |
Focal cortical ischemia (photothrombosis model) in rat |
Postlesional treatment with 1,25(OH)2D3 (4 μg/kg i.p.) | ↑glial HO-1 ↓GFAP |
[115] |
Focal cortical ischemia (photothrombosis model) in rat | 1,25(OH)2D3 (4 μg/kg i.p.) | no significant differences between 1,25(OH)2D3-treated and solvent-treated lesioned rats in neuronal COX-2 expression |
[116] |
MCAO model in female rat | Vit. D deficiency (VDD) diet for 8 weeks before MCAO; 10 μg/kg 1,25(OH)2D3, 4 h after MCAO and every 24 h thereafter for 5 days |
VDD diet effects: ↑cortical and striatal infarct volumes, ↑severe poststroke behavioral impairment ↓IGF-I in plasma and the ischemic hemisphere, ↓IL-1α, IL-1β, IL-2, IL-4, IFN-γ, and IL-10 expression in ischemic brain tissue, ↑IL-6 Acute 1,25(OH)2D3 treatment did not improve infarct volume or behavioral performance |
[117] |
Hypoxia/reoxygenation (H/R) model in bEnd.3 cells | 1,25(OH)2D3 (5–200 nmol/L)/24 h before H/R, continued throughout the H/R period | ↑BBB function, zonula occludin-1, claudin-5, and occludin, ↓NF-κB ↓MMP-9 |
[118] |
MCAO model in rat | 1,25(OH)2D3 i.p. one group—12 μg/kg immediately after the ischemia period (60 min) second group—2 μg/kg after MCAO and over the next 5 days | ↓brain infarction volume, brain edema formation ↑BBB function ↑antioxidant enzyme activities ↓cell apoptosis ↑BDNF immunoreactivity |
[119] |
MCAO rat model | Vit. D3, 1000 IU/kg/day through gavage/14 days |
↓the size of cerebral infarction, ↑cerebral perfusion in the ischemic area ↑levels of vascular growth-related factor ↑micro-vessel density after cerebral infarction and ↑the proliferation of vascular endothelial cells in the ischemic cortex ↑Shh signaling in the ischemic cortex |
[120] |
MCAO rat model | Vit. D3 100 ng/kg i.v., vit. D3 nanoemulsion i.v. and intranasal (a mean size range of 49.29 ± 10.28 nm, equivalent to 100 ng/kg vit. D3 | ↑BBB permeation, deposition, and efficacy of vit. D3-nanoemulsion through the intranasal route in comparison i.v. vit. D3 or vit. D3 nanoemulsion |
[121] |
MCAO model in C57BL6 mice | 1,25(OH)2D3 (100 ng/kg, i.p./day/5 days before MCAO | ↓the volume of cerebral infarction ↓IL-6, IL-1β, IL-23a, TGF-β, Gp91phox |
[106] |
MCAO combined with CUMS in mice | Vit. D3 (6–50 μg/kg), icv/4 weeks | ↓motor dysfunction and depression-like behaviors ↑VDR expression and BDNF |
[15] |
tMCAO model in rat | Calcitriol 1 µg/kg, i.p., 7 consecutive days before experimental induction of stroke | ↓infarction volume ↓neurological deficits in brain, ↓MDA and NO levels ↑TAC level, ↑HO-1 and Nrf2 protein and mRNA |
[124] |
↑: increase; ↓: decrease; 1,25(OH)2D3: calcitriol; BBB: blood brain barrier; BCAO: bilateral common carotid occlusion; BDNF: brain derived neurotrophic factor; bEnd.3: an immortalized mouse brain endothelial cell line; COX-2: cyclooxygenase 2; CUMS: chronic unpredicted mild stress; DHA: dehydroascorbic acid; ERK1/2: extracellular signal-regulated kinase 1 and 2; GCI: global cerebral ischemia; GDNF: glial cell-derived neurotrophic factor; GFAP: glial fibrillary acidic protein; Gp91phox: the NOX family of NADPH oxidases; GSH: glutathione; HO-1: heme oxygenase; i.p.: intraperitoneal; I/R: ischemia/reperfusion; MCA: middle cerebral arterial; MCAO/R: middle cerebral artery occlusion/reperfusion model; MDA: malondialdehyde; MEK: mitogen-activated protein kinase; MMP9: matrix metalloproteinases 9; NAC: N-acetylcysteine; NO: nitric oxide; NR3A: NMDA receptor subunit 3A; Nrf2: nuclear factor erythroid 2-related factor 2; p-CREB-Ca2+: response element binding protein; PD98059: p-ERK1/2 inhibitor; Shh: sonic hedgehog pathway; SOD: superoxide dismutase; TAC: total antioxidant capacity; TrkB: tyrosine receptor kinase B; VDR: vitamin D receptor.