<p>Ischemic stroke poses a significant threat due to its high mortality and disability rates, mainly because of the narrow therapeutic window associated with a complex inflammatory response process and blood brain barrier (BBB) disruption. Therefore, inhibiting the inflammatory response or restoring BBB integrity could potentially salvage brain tissue. Interleukin-17A (IL17A) is recognized as an initiator of inflammatory signaling and is implicated in the post-ischemic stroke inflammatory cascade. However, further exploration is needed to fully understand its underlying mechanisms. This study aims to investigate how IL17A as an inflammatory factor regulates angiogenesis to exacerbate BBB permeability and brain injury, thus shedding light on the potentially detrimental mechanism of IL17A in ischemic stroke. A mouse model of middle cerebral artery occlusion was established, with the experimental group the experimental group receiving intracerebral injections of recombinant murine IL17A. Neurobehavioral functions were assessed using Longa scoring, infarct volume was quantified via 2,3,5-triphenyltetrazolium chloride staining, and western blot analysis was conducted to evaluate the expression levels of proteins. Immunohistochemistry was employed to examine CD31, Claudin 5 and Iba-1 correlations, while tail vein injection of Evans Blue and IgG staining were utilized to assess BBB permeability. Transmission electron microscopy was employed to observe tight junction structures. Cellular experiments involved in bEnd.3 cells, ATP measurements using kits, and TUNEL staining to evaluate apoptosis. IL-17A promotes post-stroke defective angiogenesis, enhances inflammatory cell infiltration, and exacerbates cerebral infarction; Defective angiogenesis in the acute phase leads to increased matrix metalloproteinase secretion, TJ degradation, and enhanced BBB permeability; IL17A-induced angiogenesis relies on glycolysis for energy provision; Glycolysis preferentially fuels cellular self-rescue mechanisms over apoptotic pathways. IL17A facilitates dependent “defective angiogenesis” during the acute phase of MCAO, intensifying inflammatory cell infiltration, and BBB permeability by upregulating MMP-9 to degrade TJs, thereby exacerbating ischemic brain injury.</p> Graphical Abstract <p><b>rmIL17A regulates “defective angiogenesis” to exacerbate brain injury.</b> IL17A activates the glycolytic pathway to produce limited ATP to promote “defective angiogenesis”, and dysfunctional blood vessels promote inflammatory cell infiltration; however, limited ATP does not affect apoptosis. IL17A promotes MMP-9 secretion to degrade TJ (Claudin 5, N-Cadherin), leading to increased BBB permeability and further aggravating inflammatory cell infiltration. (BBB: blood brain barrier; TJ: tight junction; HK2: Hexokinase 2; PFKM: Recombinant Phosphofructokinase Transformant Muscle; PKM: Pyruvate kinase isozyme; MMP-9: Matrix metalloproteinase-9)</p> <p></p>