Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Beretta, S., Versace, A., Carone, D., Riva, M., Dell'Era, V., Cuccione, E., et al. (2017). Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 37(10), 3344-3354 [10.1177/0271678X16688705].

Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies

Beretta, S
Primo
;
Carone, D;Riva, M;Cuccione, E;Monza, L;Padovano, G;Presotto, L;Rossi, E;Giussani, C;Sganzerla, E;Ferrarese, C
Ultimo
2017

Abstract

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.
Articolo in rivista - Articolo scientifico
Acute ischemic stroke; cerebral collaterals; collateral therapeutics; experimental stroke; ischemic penumbra
English
2017
37
10
3344
3354
reserved
Beretta, S., Versace, A., Carone, D., Riva, M., Dell'Era, V., Cuccione, E., et al. (2017). Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 37(10), 3344-3354 [10.1177/0271678X16688705].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/146765
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