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Table 2 Potential strategies for modulation of cerebral collateral flow in acute ischemic stroke

From: Cerebral collateral circulation in experimental ischemic stroke

Strategies Risks Cost Results in preclinical stroke models Results and feasibility in human stroke
Pressure load
 Induced hypertension Haemorrhagic transformation, cardiac arrhythmias, myocardial ischemia Low Core and penumbra CBF augmentation through LMAs after distal MCAO in mice [43] Preliminary results indicate efficacy (small clinical studies) [44, 45]. High feasibility
Intravascular volume load
 Dextran and hydroxyethyl starch Anaphylaxis, pulmonary edema, platelet dysfunction Low CBF augmentation and improved outcome in various stroke models [46] No benefit in early clinical trials (before the introduction of recanalization therapies) [47]. High feasibility
 Albumin Pulmonary edema, allergic reactions Moderate Cerebral perfusion enhancement through LMAs after distal MCAO in mice [48, 49] No benefit in a large RCT (administered after recanalization therapy) [50]. High feasibility
Cerebral vasodilation
 Nitric oxide inhalation Pulmonary irritation Moderate Selective arteriolar vasodilation in the penumbra and cortical CBF enhancement after MCAO in mice [52] No results available in human stroke. Moderate feasibility (inhalation delivery equipment needed)
 Sphenopalatine ganglion stimulation Invasive (minor surgery) High Cortical arterioles vasodilation and CBF augmentation after photothrombosis [53] Ongoing clinical trial [54]. Moderate feasibility (surgery needed)
 Sensory-induced vasodilation No risks known Low Gradual reperfusion through collaterals after MCAO in rats [56] No results available in human stroke. High feasibility
 Acetazolamide Paraesthesia, nausea, metabolic acidosis Low Negative effect on outcome if administered 48-54 h after the onset of permanent MCAO [59] No results available in human acute stroke. Clinically used as diagnostic tool in chronic stroke. High feasibility
Cerebral flow diversion
 Head down tilt Increase in intracranial venous pressure Low Cerebral perfusion augmentation after bilateral CCAO in mice [62] Increase in cerebral perfusion and blood flow velocity by flat head positioning (case series) [60, 61]. High feasibility
 Partial aortic occlusion Invasive (endovascular surgery) High Blood flow enhancement through LMAs after thromboembolic MCAO in rats [63] Clinical trial suggest efficacy in post hoc subgroup analysis (further confirmation required) [64]. Moderate feasibility (endovascular procedure needed)