Based on these data and other results not discussed here (An et al., 2014), we propose a model whereby tPA either released in the synaptic cleft following the onset of cerebral ischemia or intravenously administered interacts with LRP1, leading to NMDAR-mediated mTOR activation, mTOR-induced HIF-1α accumulation, HIF-1α-induced recruitment of the neuronal transporter of glucose GLUT3 to the neuronal plasma membrane, and GLUT3-mediated uptake of glucose by neurons in the ischemic brain (Figure 1). This evidence concerns the gene HIF1A and brain ischemia.