Local arterial administration of acidified malonate as an adjunct therapy to mechanical thrombectomy in ischaemic stroke

Abstract

Aims Ischaemic stroke is increasingly treated by mechanical thrombectomy (MT) with the more rapid and complete reperfusion of the ischaemic tissue enhancing patient outcome, compared to recombinant tissue plasminogen activator (rtPA) alone. Even so, there is still extensive brain infarction and disability following MT, that is exacerbated by ischaemia-reperfusion injury (IRI) and other pathological processes during reperfusion. Hence, an adjunct therapy to MT that decreases IRI should enhance patient outcomes. Methods and Results To test this possibility, we adapted the transient middle cerebral artery occlusion (tMCAO) mouse model to allow local intra-arterial administration of acidified disodium malonate (aDSM) to decrease IRI as the ischaemic tissue was reperfused. Administration of aDSM (160 mg/kg; pH 6) during reperfusion decreased brain infarct volume by ∼60 % when assessed by magnetic resonance imaging (MRI) 24 h after reperfusion and improved neurological function. Conclusion These findings suggest aDSM as a potential adjunct therapy to further improve outcomes for stroke patients treated by MT.