Serum adropin levels in patients with acute ischemic stroke

Günaydın, Mücahit; Aygün, Ali; Usta, Murat; Vural, Aslı; Ozsahin, Faruk

doi:10.5455/medscience.2019.08.9072

“…Our findings are the first to reveal that adropin levels are significantly reduced in the ischemic brain from 4 to 48 hours, which is associated with a decrease in plasma adropin at 48h in mice following ischemic stroke. These results align with findings from a recent report showing lower serum adropin in patients with acute ischemic stroke (17). However, this differs from another study where transient MCAO does not change plasma adropin levels in streptozotocin-induced diabetic rats.…”

Section: Discussionsupporting

confidence: 89%

“…Adropin protein levels in the brain and plasma decrease with the aging of rats (13), mice (14), and humans (15,16). A recent study found lower serum adropin levels in patients with acute ischemic stroke compared to controls (17).…”

Section: Introductionmentioning

confidence: 99%

Adropin confers neuroprotection and promotes functional recovery from ischemic stroke

Yang

¹

,

Lavayen

²

,

Liu

³

et al. 2021

Preprint

0

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Adropin is a highly-conserved peptide that has been shown to preserve endothelial barrier function. Blood-brain barrier (BBB) disruption is a key pathological event in cerebral ischemia. However, the effects of adropin on ischemic stroke outcomes remain unexplored. Hypothesizing that adropin exerts neuroprotective effects by maintaining BBB integrity, we investigated the role of adropin in stroke pathology utilizing loss- and gain-of-function genetic approaches combined with pharmacological treatment with synthetic adropin peptide. Stroke decreased endogenous adropin levels in the brain and plasma. Adropin treatment or transgenic adropin overexpression robustly reduced brain injury and improved long-term sensorimotor and cognitive function in young and aged mice subjected to ischemic stroke. In contrast, genetic deletion of adropin exacerbated ischemic brain injury. Mechanistically, adropin neuroprotection depends on endothelial nitric oxide synthase and is associated with reduced BBB permeability and neuroinflammation. We identify adropin as a novel neuroprotective peptide with the potential to improve stroke outcomes.

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“…19 Our recent findings demonstrated that age is consistently associated with reduced levels of adropin in the brain and plasma in rats 8 and humans. 9 Reduced levels of adropin were observed in the ischemic mouse brain and plasma, 6 and serum adropin levels were significantly lower in stroke patients than those in healthy individuals, 10 suggesting that adropin might modulate stroke outcomes. In line with this point, our recent findings revealed that genetic deletion of adropin exacerbates brain injury.…”

Section: Discussionmentioning

confidence: 99%

“…4 It is highly expressed in the brain 5,6 and has been shown to preserve endothelial barrier function. 6,7 Aging or ischemic stroke is associated with reduced levels of adropin in the brain or plasma in rodents 6,8 and humans 9,10 . Our recent findings revealed that genetic deletion of Enho exacerbated ischemic brain injury, whereas transgenic overexpression of adropin or treatment with synthetic adropin peptide provided long-lasting neuroprotection following permanent middle cerebral artery occlusion (pMCAO).…”

mentioning

confidence: 99%

Therapeutic Benefits of Adropin in Aged Mice After Transient Ischemic Stroke via Reduction of Blood-Brain Barrier Damage

Yang

¹

,

Liu

²

,

Lavayen

³

et al. 2023

Stroke

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Background: Adropin is a peptide encoded by the energy homeostasis-associated gene ( Enho ) that is highly expressed in the brain. Aging and stroke are associated with reduced adropin levels in the brain and plasma. We showed that treatment with synthetic adropin provides long-lasting neuroprotection in permanent ischemic stroke. However, it is unknown whether the protective effects of adropin are observed in aged animals following cerebral ischemia/reperfusion. We hypothesized that adropin provides neuroprotection in aged mice subjected to transient middle cerebral artery occlusion. Methods: Aged (18–24 months old) male mice were subjected to 30 minutes of middle cerebral artery occlusion followed by 48 hours or 14 days of reperfusion. Sensorimotor (weight grip test and open field) and cognitive tests (Y-maze and novel object recognition) were performed at defined time points. Infarct volume was quantified by 2,3,5-triphenyltetrazolium chloride staining at 48 hours or Cresyl violet staining at 14 days post–middle cerebral artery occlusion. Blood-brain barrier damage, tight junction proteins, and MMP-9 (matrix metalloproteinase-9) were assessed 48 hours after middle cerebral artery occlusion by ELISA and Western blots. Results: Genetic deletion of Enho significantly increased infarct volume and worsened neurological function, whereas overexpression of adropin dramatically reduced stroke volume compared to wild-type controls. Postischemic treatment with synthetic adropin peptide given at the onset of reperfusion markedly reduced infarct volume, brain edema, and significantly improved locomotor function and muscular strength at 48 hours. Delayed adropin treatment (4 hours after the stroke onset) reduced body weight loss, infarct volume, and muscular strength dysfunction, and improved long-term cognitive function. Postischemic adropin treatment significantly reduced blood-brain barrier damage. This effect was associated with reduced MMP-9 and preservation of tight junction proteins by adropin treatment. Conclusions: These data unveil a promising neuroprotective role of adropin in the aged brain after transient ischemic stroke via reducing neurovascular damage. These findings suggest that poststroke adropin therapy is a potential strategy to minimize brain injury and improve functional recovery in ischemic stroke patients.

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“…Adropin protein levels in the brain and plasma decrease with the aging of rats [ 13 ], mice [ 14 ], and humans [ 15 , 16 ]. A recent study found lower serum adropin levels in patients with acute ischemic stroke compared to controls [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Neurovascular protection by adropin in experimental ischemic stroke through an endothelial nitric oxide synthase-dependent mechanism

Yang

¹

,

Lavayen

²

,

Liu

³

et al. 2021

View full text Add to dashboard Cite

Adropin is a highly-conserved peptide that has been shown to preserve endothelial barrier function. Blood-brain barrier (BBB) disruption is a key pathological event in cerebral ischemia. However, the effects of adropin on ischemic stroke outcomes remain unexplored. Hypothesizing that adropin exerts neuroprotective effects by maintaining BBB integrity, we investigated the role of adropin in stroke pathology utilizing loss- and gain-of-function genetic approaches combined with pharmacological treatment with synthetic adropin peptide. Long-term anatomical and functional outcomes were evaluated using histology, MRI, and a battery of sensorimotor and cognitive tests in mice subjected to ischemic stroke. Brain ischemia decreased endogenous adropin levels in the brain and plasma. Adropin treatment or transgenic adropin overexpression robustly reduced brain injury and improved long-term sensorimotor and cognitive function in young and aged mice subjected to ischemic stroke. In contrast, genetic deletion of adropin exacerbated ischemic brain injury, irrespective of sex. Mechanistically, adropin treatment reduced BBB damage, degradation of tight junction proteins, matrix metalloproteinase-9 activity, oxidative stress, and infiltration of neutrophils into the ischemic brain. Adropin significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS), Akt, and ERK1/2. While adropin therapy was remarkably protective in wild-type mice, it failed to reduce brain injury in eNOS-deficient animals, suggesting that eNOS is required for the protective effects of adropin in stroke. These data provide the first causal evidence that adropin exerts neurovascular protection in stroke through an eNOS-dependent mechanism. We identify adropin as a novel neuroprotective peptide with the potential to improve stroke outcomes.

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Serum adropin levels in patients with acute ischemic stroke

Cited by 4 publications

References 0 publications

Adropin confers neuroprotection and promotes functional recovery from ischemic stroke

Adropin confers neuroprotection and promotes functional recovery from ischemic stroke

Therapeutic Benefits of Adropin in Aged Mice After Transient Ischemic Stroke via Reduction of Blood-Brain Barrier Damage

Neurovascular protection by adropin in experimental ischemic stroke through an endothelial nitric oxide synthase-dependent mechanism

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