Evolucollateral dynamics in stroke: Evolutionary pathophysiology, remodelling and emerging therapeutic strategies

Abstract Leptomeningeal collaterals (LMCs) are crucial in mitigating the impact of acute ischemic stroke (AIS) by providing alternate blood flow routes when primary arteries are obstructed. This article explores the evolutionary pathophysiology of LMCs, highlighting their critical function in stroke and the genetic and molecular mechanisms governing their development and remodelling. We address the translational challenges of applying animal model findings to human clinical scenarios, emphasizing the need for further research to validate emerging therapies—such as pharmacological agents, gene therapy and mechanical interventions—in clinical settings, aimed at enhancing collateral perfusion. Computational modelling emerges as a promising method for integrating experimental data, which requires precise parameterization and empirical validation. We introduce the ‘Evolucollateral Dynamics’ hypothesis, proposing a novel framework that incorporates evolutionary biology principles into therapeutic strategies, offering new perspectives on enhancing collateral circulation. This hypothesis emphasizes the role of genetic predispositions and environmental influences on collateral circulation, which may impact therapeutic strategies and optimize treatment outcomes. Future research must incorporate human clinical data to create robust treatment protocols, thereby maximizing the therapeutic potential of LMCs and improving outcomes for stroke patients.