The goal of this Phase I unblinded, dose-escalation trial is to evaluate the safety and tolerability of intra-arterial magnesium sulfate injection after mechanical thrombectomy in patients experiencing acute ischemic stroke. This trial is one of the first trials to look at IA administration of magnesium sulfate into at risk brain tissue in a selective and localized fashion.

Patients meeting inclusion and exclusion criteria will undergo a baseline neurologic assessment and will be enrolled following informed consent. The patient will then be taken to the Interventional Radiology suite where the patient will undergo MT as per the standard of care. Participation in this study will never delay the timely provision of urgent MT to patients.

Additionally, as part of the study procedure, the patient will be assigned to Treatment Group 1,2, 3 or 4 based on the consecutive sampling scheme. The first 6 patients enrolled will be in group 1 and receive the lowest dose of MgSO4 as described below. If the analysis of this group deems this dosage to be safe, the following patients will be enrolled into group 2. The same scheme will be followed until all 4 groups are enrolled.

Patients in all groups will receive IA MgSO4 as follows (investigational):

Patients in each group will receive the specified dose of MgSO4 (listed below) diluted in 0.9% sodium chloride. The infusion of IA MgSO4 will be administered over 1-2 minutes.

Dose Escalation Schedule Group 1 0.25g IA MgSO4 Group 2 0.5g IA MgSO4 Group 3 1g IA MgSO4 Group 4 1.5g IA MgSO4

Given the minimal safety data on IA MgSO4, this dosage regimen was derived from previous IV MgSO4 studies and a singular IA MgSO4 study in a separate population to cautiously investigate the safety and tolerability for IA MgSO4.

Following MT and IA infusion, patients will receive a continuous infusion of IV MgSO4 for 24 hours. The maintenance infusion will contain 16g of MgSO4 diluted in 240 ml of 0.9% normal saline, infused at a rate of 10 ml per hour for 24 hours. Patients will follow the standard of care monitoring for post-MT patients with the addition of monitoring for magnesium toxicity.

All pre and post imaging is standard of care for this procedure, including follow up MRI (or CT if MRI contraindicated).

Following discharge from the hospital, all patients enrolled in the study protocol will be followed up in the clinic at 3 months to evaluate the patient's functional clinical outcome. If for any reason, the patient cannot come back for a follow-up visit, the PI/Co-PI's will contact the patient via phone/email to gather the required data. A minimum of mRS and NIHSS should be gathered for follow-up data.

Inclusion Criteria:

1. Patient with acute cerebral ischemia due to ICA or MCA occlusion
2. Major neurologic deficits: 6≤NIHSS≤20,
3. Premorbid mRS 0 or 1, or 2
4. Patient's clinical attending physician plans MT procedure as part of routine clinical care,
5. undergo MT with a TICI 2a or better recanalization,
6. Signed informed consent.

Exclusion Criteria:

1. Positive pregnancy test;
2. those undergoing MT with a TICI <2a revascularization;
3. tandem occlusion of the cervical common or internal carotid artery; and
4. subjects on therapeutic anticoagulation, as it is a relative contraindication to MT, and could be a confounding variable predisposing to intracranial hemorrhage including coagulation disorders, systematic hemorrhagic tendency, thrombocytopenia <80000/mm3;
5. Second or third-degree heart block without a pacemaker in place,
6. Technical inability to navigate micro-catheter to target clot,
7. Patient already enrolled in another experimental treatment trial. Exclusion criteria 1-3 are all contraindications to magnesium therapy,
8. mRS>2 caused by a history of prior stroke,
9. Severe hepatic dysfunction, severe renal dysfunction (<30 mL/min), increase in ALT or AST (more than 2 times of upper limit of normal value), increase in serum creatinine (more than 1.5 times of upper limit of normal value) or requiring dialysis;
10. Unsuitable for this clinical study assessed by researcher. Subjects will not be excluded if they received IV t-PA as standard of care.
11. patient is on neuromuscular blocking agents including depolarizing (succinylcholine) and nondepolarizing subtypes (rocuronium, vecuronium, etc);
12. patient is taking any form of CNS depressant including barbiturates, narcotics, outside the setting of anesthesia or ICU sedation
13. patients taking digoxin or other cardiac glycoside