"Time Is Brain" - for Cell Therapies

The principle "time is brain" has long guided acute stroke treatment, emphasizing that earlier intervention improves outcomes. While this dictum applies to current gold-standard reperfusion therapies, its relevance to emerging regenerative approaches such as stem cell therapy remains to be established. A growing body of preclinical and clinical studies suggests that timing of cell delivery is a key determinant of graft survival, integration and therapeutic efficacy, largely through interactions with the evolving post-stroke microenvironment. Here, we discuss how early transplantation may access salvageable tissue but faces a hostile inflammatory microenvironment, whereas transplantation at the subacute or chronic phase benefits from a more permissive milieu but by then much of the tissue has been irreversibly lost. We further suggest the optimal window also depends on cell type and mechanism of action: neuroprotective or immunomodulatory grafts may benefit from earlier delivery, while cells requiring long-term survival and integration may perform better later. Thus, "time is brain" also applies to cell therapies, but it may require aligning graft delivery with the evolving post-stroke microenvironment rather than the acute therapeutic window. Identifying biomarkers that track inflammatory changes, vascular remodeling and brain damage could personalize this "window of receptivity" and guide tailored future clinical trials.