The objective of this clinical trial is to determine whether rapid local ischemic postconditioning (RL-IPostC) is effective in preventing brain edema and safe in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. In this trial, researchers will block antegrade cerebral blood flow temporarily by the way of balloon inflation/deflation in AIS patients immediately after revascularization. It makes the ischemic reperfusion brain tissue have a capacity of adaptation through intermittent blood flow restoration. Researchers will evaluate the protective role and safety of different duration of balloon inflation/deflation. The optimal postconditioning intervention dose will be determined for further confirmative investigation.

This will be an umbrella trial of testing the efficacy and safety of three postconditioning intervention doses. It will be a prospective, open-label, blinded endpoint, three-dose Bayesian Optimal Phase 2(BOP2) design trial with interim efficacy and safety monitoring. The maximum number of subjects for this trial is estimated as 135 patients. Eligible patients are 18 years or older with symptomatic large vessel occluded (LVO) AIS treated with mechanical thrombectomy (MT) achieving successful reperfusion defined as mTICI score 2b or 3. Patients will receive 5 cycles of balloon inflation/deflation at ipsilateral C1 segment of internal carotid artery (ICA) for the temporary occlusion of the restoration of antegrade blood flow. Three postconditioning intervention doses of 30s/30s, 60s/60s and 180s/180s were adopted for block and restore of blood blow. The primary outcome is a favorable binary outcome defined as no clinically meaningful brain swelling from baseline to 24 hours and no clinically meaningful infarction growth from baseline to 24 hours and no causally attributable serious adverse events (SAEs). It's a composite outcome of efficacy and safety outcome. Key secondary outcomes include efficacy outcome indicating no clinically meaningful brain swelling defined by cerebral spinal fluid (CSF) volume reduction≤5 mL from baseline to 24 hours and safety outcome indicating infarct volume growth>10 mL from baseline to 24 hours or causally attributable SAEs. Other secondary outcomes include change of brain net water uptake, midline shift and functional outcome. For each intervention dose, we will perform the interim analyses following pre-defined optimized Bayesian rule for early stopping to make a go/no-go decision when the number of enrolled patients reaches 10, 20, 30. The optimal intervention dose will be determined according to the number of patients reach the primary endpoints in different groups.

Inclusion Criteria:

1. Age ≥ 18 years old
2. Presenting with symptoms consistent with acute ischemic stroke
3. Pre-stroke mRS score 0-1
4. Baseline NIHSS score≥6
5. Endovascular treatment can be initiated (femoral puncture) within 24 hours from stroke onset (stroke onset time is defined as last known well time)
6. Occlusion of the intracranial internal carotid artery, or the middle cerebral artery(M1 or M2) confirmed by CTA or MRA, and is the culprit artery
7. Alberta Stroke Program Early CT Score (ASPECTS) (based on non-contrast CT) >5 on noncontrast computed tomography (NCCT) for stroke onset time less than 6 hours, infarct Core < 70 ml (defined as rCBF <30% on CT perfusion) and mismatch ratio > 1.2 (penumbra defined as Tmax >6 seconds volume) for stroke onset time between 6 and 24 hours.
8. Embolism verified as the etiology of occluded artery and mTICI 2b or 3 regained after mechanical thrombectomy
9. Informed consent signed

Exclusion Criteria:

1. Stenosis of the proximal middle cerebral artery, internal carotid artery, or common carotid artery (≥50%) of the culprit artery
2. Multiple vascular embolism on different pathways (not refers to the ipsilateral middle artery and anterior artery)
3. Pre ischemic stroke or transient ischemic attack within past 3 months
4. The expected survival time is less than 6 months, could not be followed at 90 days (such as patient with malignant tumor)
5. Currently pregnant, mental disease, advanced hepatic and renal insufficiency, severe heart failure
6. Participation in other interventional randomized clinical trials that may confound the outcome assessment of the trial
7. Other circumstances that the investigator considers inappropriate for this trial