COOLing of the Ischemic PENumbra in Patients With Acute Ischemic Stroke.

This study will develop and validate a novel, active/conductive combined head and neck cooling system to selectively cool the ischemic penumbra during the acute phase of stroke, reducing neuronal damage and improving stroke outcomes. It complements existing reperfusion therapies offering a scalable neuroprotective option which will have wider implications across diverse healthcare settings. PHASE I: Technology Development \& Test Bench Optimization (Years 1-2) PHASE II: Validation in healthy volunteers (Year 3) PHASE III: Pilot, multicenter, randomized controlled (Phase 2a) trial (Year 4-5):

Inclusion Criteria: PHASE l 1. Healthy adult participants of any gender aged 18 years or older and able to provide 2. informed consent. PHASE II 1\. Adult patients of any gender, presenting with acute ischemic stroke and eligible for reperfusion therapy IVT or EVT or Both as per guidelines. Exclusion Criteria: PHASE I 1. History of uncontrolled hypertension or cardiovascular disease. 2. Hematologic dyscrasias that can affect thrombosis like cryoglobulinemia or sickle cell disease or serum cold agglutinins. 3. Vasospastic disorders like Raynaud or thromboangiitis obliteran. 4. Skin lesions not allowing secure application of the cooling system PHASE II 1. Surface Body temperature less than and equal to 35 degree Celcius at baseline 2. Blood pressure more than or equal to 185 by 110 mmHg not responsive to guideline-directed intravenous antihypertensive therapy 3. Known contraindications to hypothermia including hemodynamically unstable patients with new or symptomatic bradyarrhythmia known hematologic dyscrasias that affect thrombosis or vasospastic disorders such as Raynaud syndrome or thrombo angiitis obliterans. 4. Skin lesions on scalp or neck preventing secure application of the cooling cap. 5. Pre-morbid mRS more than or equal to 3 6. Patients with known diseases or conditions resulting in an expected life expectancy of less than or equal to 3 months