From emergency myelopoiesis to trained immunity? Reframing post-stroke myeloid reprogramming along the brain-bone marrow axis

Ischemic stroke rapidly mobilizes myeloid cells from anatomically distinct bone-marrow niches, while emerging evidence indicates that severe cerebral injury can also leave a durable imprint on hematopoiesis. These observations have encouraged the use of the term trained immunity in stroke biology, but acute myeloid expansion is not equivalent to innate immune memory. In this Mini review, we distinguish acute myeloid activation, myelopoietic responses consistent with emergency myelopoiesis, and central trained immunity involving hematopoietic stem and progenitor cells (HSPCs). We use an operational four-feature framework-persistence, progenitor involvement, epigenetic or metabolic reprogramming, and functional recall-to grade the strength of current evidence. We consider a sequential transition from emergency myelopoiesis to trained immunity as one testable possibility rather than an established pathway, while allowing for parallel or independent mechanisms. The key unresolved questions are where durable memory is stored, when acute hematopoietic adaptation becomes stabilized, and which outputs are maladaptive versus reparative. Resolving these boundaries is essential before marrow-directed immunomodulation can be translated to patients with ischemic stroke.