Abstract A149: Myeloid-Specific Deletion Of Pyruvate Kinase M2 Improves Neurological Recovery In a Murine Model Of Hemorrhagic Stroke

Introduction: In intracerebral hemorrhage (ICH), inflammation driven by myeloid cells plays a major role in neuronal damage and poor neurological recovery. Current therapies primarily target hypertension and intracranial pressure, with limited focus on promoting hematoma resolution. The metabolic enzyme pyruvate kinase M2 (PKM2) is known to regulate inflammation, but its role in erythrophagocytosis-mediated hematoma clearance remains unclear. Hypothesis: Targeting PKM2 in myeloid cells will promote hematoma clearance via enhanced erythrophagocytosis, thereby reducing inflammation and improving neurological recovery in an ICH model. Methods: ICH was induced in 15–20-week-old male myeloid-specific PKM2 –/– mice (PKM2 fl/fl LysMCre + , referred to as PKM2 Mye-KO ) and littermate controls (PKM2 fl/fl , referred to as PKM2 WT ) via striatal injection of collagenase IV. Structural brain changes were assessed using MRI. Functional outcomes were evaluated at week 1, 2, 3, and 4 post-injury using functional tests (mNSS, corner, rotarod, Y-maze, and novel object recognition). On day 4 post-ICH, expression of Il1β , Tnfα , Arg1, Cx3cr1, and p-STAT3 in microglia/macrophages isolated from the (peri)hematomal region was quantified by qPCR, while the expression of efferocytosis receptors AXL, CD36, and MERTK was evaluated by flow cytometry. In vitro erythrophagocytosis was assessed via immunohistochemistry. Results: PKM2 Mye-KO mice exhibited reduced brain edema and infarct volumes from day 2 to 28 post-ICH (P