Central Control of Stress Networks in Stroke-Heart Syndrome: An Innovative Target for Therapeutic Interventions

• Applicant: Dr. Isra Tamim
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 571559227

Stroke-heart syndrome (SHS) refers to the acute and chronic cardiac complications that frequently follow ischemic stroke, contributing substantially to post-stroke morbidity and mortality. Despite their clinical significance, the central mechanisms that translate cerebral ischemia into peripheral cardiac injury remain poorly understood. This project aims to elucidate how stroke-induced activation of central stress circuits orchestrates peripheral stress responses that ultimately lead to cardiac dysfunction. The applicant’s preliminary data show that stroke rapidly induces troponin release, impairs cardiac function, and mobilizes neutrophils to the heart. Simultaneously, key brain regions such as the locus coeruleus (LC) and the paraventricular nucleus (PVN)—major regulators of systemic stress responses are strongly activated. The research pursues three primary objectives: (1) to generate an unbiased, brain-wide map of neuronal activation following stroke using iDISCO/ClearMap and RNAScope technologies; (2) to define the functional roles of activated stress centers in modulating immune responses through chemogenetic and optogenetic gain- and loss-of-function approaches; (3) to therapeutically target peripheral pathways downstream of central activation, including HPA-axis and β-adrenergic signaling and neutrophil recruitment, in order to prevent or attenuate cardiac injury. The experimental framework combines cutting-edge tools in neuroimmunology, including flow cytometry, echocardiography, and targeted pharmacological and genetic interventions in mouse models. Findings will be cross-validated using clinical datasets featuring immune phenotyping and cardiac assessments. By establishing a mechanistic link between brain-mediated stress signaling and cardiac injury after stroke, this project seeks to uncover novel therapeutic strategies for SHS. Its interdisciplinary design—at the interface of neurology, cardiology, and immunology—offers high translational potential for advancing both experimental models and clinical care in stroke medicine.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Wolfram Christian Poller, Ph.D.