Anisodine hydrobromide targets matk and prevents delayed rtPA thrombolysis-induced vasogenic cerebral edema in ischemic stroke

Vasogenic cerebral edema is a severe complication of delayed thrombolysis for ischemic stroke, for which no pharmacological treatment exists. Anisodine hydrobromide (Ani), an alkaloid used clinically in China for vascular disorders, is investigated for its potential to mitigate this condition. Here we show that Ani treatment improves survival and neurological function in a mouse model of delayed rtPA-induced cerebral edema by preserving the integrity of the blood-brain barrier. Utilizing proteomics and microarray screening, we identify megakaryocyte-associated tyrosine kinase (Matk) as a direct target of Ani. We demonstrate that Ani binding stabilizes Matk, preventing its degradation and suppressing the activation of Src kinase. This inhibition consequently blocks the dual paracellular and transcellular leakage pathways that drive vasogenic edema. Our findings reveal the Matk-Src signaling axis as a therapeutic target and support Ani as a promising clinical candidate for preventing post-thrombolytic complications in stroke management. Ischemic stroke treatment can be complicated by brain edema if thrombolytic drugs are given too late. Here, the authors show that anisodine hydrobromide mitigates this dangerous edema in mice by targeting the Matk-Src pathway to protect blood vessels in the brain