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. Author manuscript; available in PMC: 2021 Aug 12.
Published in final edited form as: Cond Med. 2020 May 5;3(2):104–115.

Table 1.

Summary of representative studies on postconditioning for ischemic stroke treatment.

Ischemia models/time period Species Sex Age or body weight Treatment time point after reperfusion Treatment Periods Cycle Molecular mechanisms Outcomes Ref
MCAO 60 min C57BL6 mice Male 23–26g 10 min 10 min I 1 Inhibited Leucocyte infiltration, microglial activation, NF-κB, MMP-9, proteasome activity; Increased HSP70.BDNF, VEGF Reduced Infarct size, BBB damage, brain edema; Improved motor function, neurogenesis, angiogenesis (Doeppner et al., 2017)
MCAO 45 min C57BL6 mice Male 4–4.5 months 2 min 15s I/30s R 3 Inhibited miR-1/−12, let-7f; Increased miR-19a Improved motor and cognitive function (Miao et al., 2016)
MCAO 120 min Wistar rats Male 7–8 weeks Immediately 30s R/30s I 3 Reduced protein carbonyl derivatives, advanced oxidation protein products, hydrogen peroxide; Increased SOD, CAT, proteasome activity Reduced infarct size (Li et al., 2012)
MCAO Wistar rats Male 200–250g 30 min 10s I/30s R 5 Decreased ROS Reduced infarct size, brain edema (Rezazadeh et al., 2013)
30s I/30s R 5 Reduced infarct size
60s I/60s R 5 Reduced infarct size
MCAO 2 hours Wistar rats Male 7–8 weeks Immediately 30s R/30s I 3 Increased IκBα, decreased p-IκBα, NF-κB, p- NF-κB, Caspase-3, Noxa, Bim and Bax Reduced infarct size, apoptosis, improved neurological outcome (Liang et al.; 2014)
MCAO 100min 5D rats Male 10 min 10 min I 1 Not studied Reduced infarct size, improved neurological outcomes, neurogenesis, and angiogenesis (Esposito et al., 2015)
MCAO 100min 5D rats Male 320–340g 10 min 10 min I 1 Increased VEGF Reduced Infarct size; Improved neurological outcome; microglial polarization (Esposito et al., 2018)
MCAO 60 min SD rats Male 250–280g Immediately 30s R/30s I 6 Increased HSP70, bcl-2, SOD activity; Decreased caspase-3/9, MDA, inhibited cytochrome C and bax translocation Reduced infarct size, and cell apoptosis; improved neurological outcomes (Xing et al., 2008a)
MCAO 2,3, 4, 4.5, 6 hours SD rats Male 7–8 weeks Immediately 10s I/10s R 5 Inhibited IL-1β, TLR2/4, IRAK4 Reduced infarct size and cell apoptosis (Wang et al., 2014)
MCAO 90 min SD rats Male 7–8 weeks 270–300g Immediately or 3 h 10s I/10s R 10 Increased BDNF, p-CREB, Reduced infarct size, brain edema, cell Hpoptosis, and stabilized cerebral blood flow (Wu et al., 2015)
MCAO 120 min SD rats Male 250–280g Immediately 30s R/30s I 3 Preserved claudin-5, occludin Reduced infarct size, protected neurovascular unit, improved neurological outcome (Han et al., 2014)
MCAO 120 min SD rats Female 2–3 months 210–230g Immediately 10s R/10s I 6 Increased acid-sensing ion channel 2a Protected neurons of hippocampal CA1 region (Duanmu et al,, 2015)
MCAO 120 min SD rats Male 250–280g Immediately 30s R/30s I 3 Inhibited AQP4 Reduced infarct size and brain edema (Han et al., 2015)
MCAO 120 min SD Rat Male 250–300g Immediately 30s R/30s I 3 Not studied Reduced infarct size (Taskapilioglu et al., 2009)
MCAO Rat Male Inhibited positive cell cycle regulators and ERK/CREB and GSK- 3β/CREB (Zhao et al., 2013)
MCAO 60 min SD Rats Male 250–230g Immediately 30s R/30s I 6 Inhibited MPO, MDA, IL-1β, TNF-α, ICAM-1 Reduced infarct size, cell necrosis and apoptosis, leucocyte infiltration and oxidative stress (Xing et al., 2008b)
MCAO 100 min SD rats Male 250–300g 2 min 2 min I/2 min R 5 Increased p-AKT, p-ERK, p-p38 No protection on infarct volume (Pignataro et al., 2008)
5 min 5 min I/5 min R 3 Reduced infarct size
10 min 10 min I 1 Reduced infarct size
30 min 10 min I 1 No protection
Thrombotic ischemia Tree shrews Male 120–150g 4 h after ischemia 5 min I/5 min R 3 Inhibited MIPO, TLR4; Increased TLR4 at 72 hours Reduced neuron death (Feng et al., 2011)
Distal MCAO plus BCCA 30 min SD rats Male 350–400g Immediately or 3 h 30s R/10s I 3 Decreased CHOP, caspase-12; Increased GRP7E, Reduced infarct size and neuronal apoptosis (Yuan et al., 2011)
Permanent distal (MCAO) plus CCAO 30 min 5D rats Male 350–390g Immediately 30s R/10s I 3 Mot mentioned Reduced brain infarct volume (Gao et al,, 2008a)
30s R/10s I 10 No protection
10s R/10s I 3 No protection
10s R/10s I 10 Reduced infarct size
3 min 10s I/10s R 10 No protection
Permanent distal (MCAO) plus CCAO 30 min SD rats Male 350–450g Immediately 30s R/10s I 3 Inhibited superoxide Reduced infarct size and cell apoptosis (Zhao et al., 2006)
Permanent distal MCAO plus bilateral CCAO 30 min SD rats; T-cell-deficient rats Male 230–250g Immediately 30s R/10s I 3 Increased p-Akt, Akt1/2/3, p-mTOR, mTOR, pS6K, S6K, p4EPB1, 4EPB1, GAP43 Reduced infarct size and improved neurological outcomes (Xie et al., 2013)
SD rats Male 350–390g Immediately 30s R/10s I 3 Increased p-Akt, p-GSK3β, p-β-catenin, p-JNK, p-ERK1/2, δPKC, εPKC Long-term reduction of brain damage and improved neurological outcomes (Gao et al., 2008b)
SD rats Male 270–330g 30 min 10s I/10s R 10 Reduced infarct size (Ren et al., 2008)
30 min 30s I/30s R 3 Reduced infarct size
3h 10s I/10s R 10 No protection
3h 30s I/30s R 3 Reduced infarct size
BCAO 10 min Swiss mice Male 25 ± 2g Immediately 10s R/10s I 3 PI3K Improved memory and motor coordination (Rehni and Singh, 2007)
BCAO 12 min Swiss mice Male 20 ± 5g Immediately 10s R/10s I 3 Increased nitrite/nitrate, GSH, eNOS; Inhibited AChE activity, TBRS Reduced infarct size, improved memory and motor coordination (Gulati et al., 2014)
BCAO 12 min Swiss mice Male 22 ± 5g Immediately 10s R/10s I 3 Increased nitrite/nitrate, GSH; Inhibited AChE activity, TBARS Reduced infarct size, improved memory and motor coordination (Gulati and Singh, 2014)
BCAO 17 min Swiss mice Either sex 25 ± 2g Immediately 10s R/10s I 3 Involved CCR2 Reduced infarct size, improved memory and motor corrdiantion (Rehni and Singh, 2012)
4-VO 10 min SD rats Male 200–220g Immediately 10s R/10s I e Inhibited caspase-3/6/9, bax; Increase bcl-2 Protected hippocampal neurons and inhibited apoptosis (Ding et al., 2012)
4-VO 10 min SD rats Male 200–220 g Immediately 10s R/10s I 6 Inhibited caspase-3/6/9, bax; Increase bcl-2 Protected hippocampal neurons and inhibited apoptosis (Ding et al., 2012)
4-VO 10 min SD rats Male 260–320g Immediately 15s R/15s I 3 Inhibited Cytochrome C translocation Promoted neuron survival, spatial learning and memory; improved the disturbance of CBF (Wang et al., 2008)
30s R/30s I 3 Inhibited Cytochrome C translocation Promoted neuron survival, spatial learning and memory; improved the disturbance of CBF
60s R/15s I 3 None None
45 s 15s I/15s R 3 Inhibited Cytochrome C translocation Promoted neuron survival, spatial learning and memory; improved the disturbance of CBF
4-VO 10 min SD rats Male 220–250g Immediately 10s R/10s I 6 Inhibited caspase-3; increased Bcl-2 Reduced hippocampal neuron apoptosis (Zhang et al., 2012)
4-VO 15 min SD rats Male 220–300g 10 min 3 min I 1 Stabilized VDAC1/2/3 expression and calcium homeostasis Protected hippocampal neurons (Yao et al., 2018)
4-VO 15 min SD rats Male 250–300g 10 min 3 mini 1 Inhibited GluK2-PSD-95-MLK3-MKK7-JNK3 Protected hippocampal CA1 pyramidal neurons (Liu et al., 2013)
4-VO 15 min Wistar rats Male 250–300g Immediately 30s R/15s I 3 Not studied Reduced neuron apoptosis and neurodegeneration (Xiang et al., 2018)
4-VO 10 min Wistar rats Male 250–300g 2 days 5 min I 1 Increased SOD and CAT activity Reduced neuronal degeneration (Danielisova et al., 2006)
4-VO 10 min Wistar Rats Male 250–350g 2 days 4 min or 6 min I 1 Increased MnSOD Not studied (Nemethova et al., 2008)
4-VO 8, 10, 12 min Wistar rats Not mentioned 250–350g 2 days 5, 6 min I 1 Not mentioned Promoted survival of CA1 neurons, cortex and striatum neurons (Burda et al., 2006)

I, Ischemia; R, Reperfusion; 4-VO, four vessel occlusion; AQP4, Aquaporin 4; BCAO, bilateral carotid artery occlusion; BDNF, Brain-derived neurotrophic factor; CAT, Catalase; CCR2, C-C chemokine receptor type 2; CHOP, C/EBP-homologous protein; GAP43, Growth Associated Protein 43; Gluk2, Glutamatergic kainate receptor subunit 2; GSH, Glutathione; HSP70, heat shock protein 70; IRAK4, Interleukin-1 receptor-associated kinase 4; JNK3, c-Jun N-terminal kinase 3; MCAO, middle cerebral artery occlusion; MDA, Malondialdehyde; MLK3, Mixed-lineage protein kinase 3; MMP-9, Matrix metallopeptidase 9; MPO, Myeloperoxidase; mTOR, mammalian target of rapamycin; PSD-95, postsynaptic density protein 95; ROS, Reactive oxygen species; SOD, Superoxide dismutase; TBARS, Tihobarbituric acid reactive species; TLR4, Toll-like receptor 4; VDAC, Voltage-dependent anion channel; VEGF, Vascular endothelial growth factor