Comprehensively, our results illustrate that the nasal administration of AS and TMP exhibits a synergistic protective effect on experimental cerebral ischemia, and the observed beneficial effects may be attributed to a proportional adjustment between TIMP-1 and MMP-9, the regulation of the HIF-1α-VEGFA pathway, and anti-inflammatory effects to attenuate BBB injury. Here, TIMP1 is linked to brain ischemia.