Inclusion Criteria1. Age 18-80 years
2. Clinical presentation of acute ischemic stroke
3. Computed tomography (CT) scan compatible with acute ischemic stroke.
4. Time to caffeinol treatment < 240 minutes from stroke onset.
5. Time to hypothermia initiation < 300 minutes from stroke onset.
6. Presumed cortical location of stroke (must have at least on sign such as aphasia, neglect, visual field cut)
7. National Institutes of Health Stroke Scale (NIHSS) > 8 at time of each treatment.
8. Tissue plasminogen activator (TPA) treated patients must meet all established criteria for TPA.
Exclusion Criteria1. Etiology other than ischemic stroke.
2. Item 1a on NIHSS > 1
3. Signs/symptoms of subcortical, brainstem or cerebellar stroke.
4. Symptoms resolving or NIHSS < 8 at time of each treatment.
5. NIHSS > 20 if right hemisphere or >25 if left hemisphere
6. Known alcoholic
7. Clinical or laboratory evidence of alcohol intoxication.
8. Historical evidence of exogenous caffeine exposure beyond daily consumption of coffee or soft drinks.
9. Known hematologic dyscrasias that affect thrombosis.
10. Comorbid conditions likely to complicate therapy:
1. End-stage cardiomyopathy
2. Uncompensated or clinically significant arrhythmia
4. Liver disease
5. History of pelvic or abdominal mass likely to compress inferior vena cava.
6. End-stage AIDS
7. History of clinically significant gastrointestinal (GI) bleeding
8. Impaired renal function with creatinine clearance, 50 ml/min
11. Intracerebral / intraventricular hemorrhage
12. Systolic blood pressure (SBP) > 210 or < 100; diastolic blood pressure (DBP) > 100 or < 50 mmHg
13. Severe coagulopathy
15. Use of monoamine oxidase inhibitor (MAOI),serotonin-specific reuptake inhibitor (SSRI) or Tricyclic Antidepressants (TCA) within the preceding 2 weeks
16. Known history of epilepsy.