Table 1.
Summary of in vivo studies on SPMs in ischemic stroke and cerebrovascular events.
| Reference | Type of Study | Animal Model | Pro-Resolving Mediator | Delivery (Or Measurement If the Study Was Non-Interventional) | Outcome |
|---|---|---|---|---|---|
| Zuo et al., 2018 [26] | Animal study | MCAO mouse model | RvD2 | intraperitoneal | ↓ infarction, inflammation, edema, and neurological dysfunction; compared with ω-3 fatty acid oral supplements, better rescue effect on cerebral infarction |
| Dong et al., 2019 [27] | Animal study | MCAO mouse model | RvD2 | Intravenous infusion of RvD2-loaded nanovesicles | ↓ inflammation; ↑ neurological function |
| Fredman et al., 2016 [30] | Animal study | fat-fed Ldlr-/- mice | RvD1 | Immunoprecipitation injection | ↓ atherosclerosis |
| Kotlęga et al., 2021 [31] | Human study | - | RvD1 | blood levels of endogenous pro-resolving mediators | Post-stroke blood levels of RvD1 correlated with a better cognitive performance |
| Xian et al., 2016 [32] | Animal study | MCAO mouse model | MaR1 | Intracerebroventricular | ↓infarct volume and neurological defects by inhibiting NF-kB p65 function |
| Xian et al., 2019 [33] | Animal study | MCAO mouse model | MaR1 | Intracerebroventricular | ↓ inflammation and mitochondrial damage via activation of SIRT1 signaling |
| Vital et al., 2020 [34] | Animal study | Lipopolysaccharide and sickle transgenic mice models of thrombo-inflammation | AnxA1 mimetic peptide Ac2-26 | Intravenous | ↓ thrombo-inflammation via Fpr2/ALX receptor and ↓ platelet aggregation |
| Gavins et al., 2007 [35] | Animal study | MCAO in wild-type or AnxA1−/− mice | AnxA1 mimetic peptide Ac2-26 | Intravenous | ↓ inflammation via receptors of the FPR family |
| Xu et al., 2021 [37] | Animal study | MCAO mouse model | AnxA1 mimetic peptide Ac2-26 | Intravenous | ↓ inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway |
| Ding et al., 2020 [38] | Animal study | Collagenase-induced ICH mouse model | Recombinant human AnXA1 | Intracerebroventricular | ↓ inflammation via the FPR2/p38/COX-2 pathway |
| Senchenkova et al., 2019 [39] | Animal study | MCAO in wild-type or AnxA1−/− mice | Whole protein AnXA1 | Intravenous | ↓ platelet aggregation by affecting integrin (αIIbβ3) activation |
| Li et al., 2021 [40] | Animal study | MCAO mouse model | LXA4 | Intracerebroventricular | ↓ proinflammatory cytokines and regulate microglial M1/M2 polarization via the Notch signaling pathway |
| Wu et al., 2013 [41] | Animal study | MCAO mouse model | LXA4 | Intracerebroventricular | ↓infarct volume and ↑ neurological function through Nrf2 upregulation |
| Hawkins et al., 2014 [43] | Animal study | MCAO mouse model | LXA4 analog BML-111 | Intravenous | ↓ infarct size, edema, BBB disruption, and hemorrhagic transformation |
| Hawkins et al., 2017 [44] | Animal study | MCAO mouse model | LXA4 analog BML-111 | Intravenous | ↓ infarct volume; and ↑ neurological function at 1 week. No reduction of infarct size or improvement of behavioral deficits 4 weeks after ischemic stroke |
| Wu et al., 2010 [45] | Animal study | MCAO mouse model | LXA4 ME | Intracerebroventricular | ↓ proinflammatory cytokines, neurological dysfunctions, infarction volume, and neuronal apoptosis |
| Ye et al., 2010 [46] | Animal study | MCAO mouse model | LXA4 ME | Intracerebroventricular | ↓ proinflammatory cytokines, neurological dysfunctions, infarction volume, and neuronal apoptosis |
| Wu et al., 2012 [47] | Animal study | MCAO mouse model | LXA4 ME | Intracerebroventricular | ↓ BBB dysfunction and MMP-9 expression; ↑ TIMP-1 expression |
| Jin et al., 2014 [48] | Animal study | BCCAO | LXA4 ME | Intracerebroventricular | Amelioration of cognitive impairment via ↓oxidative injury and ↓neuronal apoptosis in the hippocampus with the activation of the ERK/Nrf2 signaling pathway |
| Wang et al., 2021 [49] | Human study | - | LXA4, RvD1, RvD2, RvE1, MaR1 | blood levels of endogenous pro-resolving mediators | ↓ LXA4 in patients with post-stroke cognitive impairment |
| Guo et al., 2016 [50] | Animal study | endovascular perforation model of SAH | Exogenous LXA4 | Intracerebroventricular | ↓ neuroinflammation by activating FPR2 and inhibiting p38 |
| Liu et al., 2019 [51] | Animal study | endovascular perforation model of SAH | Recombinant LXA4 | Intracerebroventricular | ↓ endothelial dysfunction and neutrophil infiltration, possibly involving the LXA4/FPR2/ERK1/2 pathway |
| Yao et al., 2013 [53] | Animal study | MCAO mouse model | NPD1 | Intracerebroventricular | ↓ infarct volume and ↑ neurological scores through inhibition of calpain-mediated TRPC6 proteolysis and activation of CREB via the Ras/MEK/ERK pathway |
| Eady et al., 2012 [54] | Animal study | MCAO mouse model | NPD1 | Intravenous | ↓ infarct size in aged rats via activation of Akt and p70S6K pathways |
| Belayev et al., 2017 [55] | Animal study | MCAO mouse model | DHA (NPD1 precursor) | Intravenous | ↓ oxidative stress by upregulating ring finger protein 146 (Iduna) in neurons and astrocyte |
| Zirpoli et al., 2021 [56] | Animal study | Unilateral cerebral hypoxia-ischemia injury mouse model | NPD1 | Intraperitoneal | ↓ ischemic core expansion, preserved mitochondrial structure and ↓ BAX translocation and activation |
| Belayev et al., 2018 [57] | Animal study | MCAO mouse model | NPD1 | Intracerebroventricular | ↑ neurogenesis and angiogenesis, BBB integrity, and long-term neurobehavioral recovery |
| Bazan et al., 2012 [58] | Animal study | MCAO mouse model | AT-NPD1 | Intravenous | ↓ infarct volume and brain edema; ↑ neurobehavioral recovery |
AnXA1: Annexin A1; AT-NPD1: aspirin-triggered NPD1; BBB: Blood–Brain Barrier; BCCAO: bilateral common carotid artery occlusion; DHA: docosahexaenoic acid; FPR: formyl-peptide receptor; LXA4: Lipoxin A4; LXA4 ME: Lipoxin A4 Methyl Ester; MaR1: Maresin1; MCAO: middle cerebral artery occlusion; NPD1: Neuroprotectin D1; RvD1: Resolvin D1; RvD2: Resolvin D2; RvE1: Resolvin E1; SAH: Sub Arachnoid Hemorrhage.