Inclusion Criteria- Sudden focal neurological deficit attributable to acute ischemic stroke.
- Age between 18 and 85.
- Time from symptom onset less than 4.5 hours.
- NIHSS score between 7 and 20.
- Informed consent for participation.
- Ketamine can be administered within 15 minutes after onset of tPA infusion.
- MRI-based AIS diagnosis.
- Middle cerebral (M1 or M2 segment) and/or distal internal carotid artery occlusion.
- No intracranial hemorrhage on MRI.
- Patient eligible for thrombectomy.
Exclusion Criteria- Contraindication to IV tPA treatment.
- Contraindication to ketamine.
- Contraindication to MRI.
- Contraindication to intravascular iodinated contrast media.
- Consciousness level >1 on question 1a of NIHSS.
- Pre-stroke mRS ≥3.
- Concomitant medical illness that would interfere with outcome assessments and follow-up (e.g. advanced cancer or respiratory disease).
- Previous participation in this trial or current participation in another investigational drug trial.
- Infarct volume on diffusion weighted MRI more than 100 mL.