Limb Remote Ischemic Postconditioning Improves Glymphatic Dysfunction After Cerebral Ischemia–Reperfusion Injury

Apr 30, 2023Neuroscience

Using brief limb blood flow interruptions after stroke may improve brain waste clearance problems

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Abstract

Cerebrospinal fluid flow is disturbed in the early stages of cerebral ischemia, leading to decreased polarization of aquaporin-4.

Delayed neuronal damage can occur after cerebral ischemia-reperfusion injury.
Glymphatic system dysfunction after such injury is associated with increased brain edema and neuroinflammation.
A decrease in aquaporin-4 polarization is observed from 12 hours to 72 hours of reperfusion.
Limb remote ischemic postconditioning may enhance aquaporin-4 polarization and reduce amyloid-β deposition.
Improving glymphatic function through limb remote ischemic postconditioning could offer neuroprotection after ischemia-reperfusion.

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BACKGROUND: Delayed neuronal damage can be caused or aggravated after cerebral ischemia-reperfusion (I/R) injury. Recent studies have shown that glymphatic system dysfunction after cerebral ischemia-reperfusion injury is involved in ischemic brain edema and neuroinflammation, thereby regulating cerebral ischemia-reperfusion injury. The aim of this study is to investigate the changes of glymphatic system after cerebral ischemia-reperfusion injury and whether limb remote ischemic postconditioning (LRIP) can improve the function of glymphatic system to protect the brain.

METHODS: To establish a focal brain I/R injury mouse model, this study utilized the middle cerebral artery occlusion/reperfusion (MCAO/R) method. The present study classified eight-week-old C57BL/6 male mice into three groups. The changes in glymphatic function in different periods of ischemia and reperfusion were analyzed through immunofluorescence, transmission electron microscopy (TEM), and Western-Blot (WB) assays. The contents of the evaluation included cerebrospinal fluid flow, swelling degree of brain tissue, aquaporin-4 (AQP4) expression and polarization, and amyloid-β (Aβ) excretion.

RESULTS: In the early stages of cerebral ischemia, cerebrospinal fluid (CSF) flow is disturbed, accompanied by a decrease in AQP4 polarization. The polarity of AQP4 decreased from 12 h to 72 h of reperfusion, the Aβ deposition. LRIP can increase the expression of β-DG and AQP4 polarization, reduce the deposition of Aβ, improve the function of the glymphatic system, and reduce the expression of AQP4 to play A protective role in brain.

CONCLUSION: Glymphatic system impaired after cerebral ischemia-reperfusion injury in mice. LRIP may play a neuroprotective role by improving glymphatic function after I/R.

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Limb Remote Ischemic Postconditioning Improves Glymphatic Dysfunction After Cerebral Ischemia–Reperfusion Injury

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