In the mammalian brain, neural stem cells and neurogenesis persist into adulthood mainly in the subependymal zone-olfactory bulb pathway and hippocampal formation. Adult neurogenesis is proposed to play an important role in learning and memory, but it also offers the potential for replacing injured or diseased brain tissues through regeneration by neural stem cells. Despite the persistence of neurogenesis, mammals have limited brain regenerative capacity. Zebrafish, however, display robust regeneration in many different brain regions and can make mature, functional neurons after injury. We use adult zebrafish to explore the molecular networks induced by traumatic brain injury and quinolinic acid (QA)-induced neurotoxicity. We performed RNA sequencing on telencephalic tissue collected 24 or 48 hours after brain injury, with or without QA lesioning, and identified many interesting candidate genes involved in various biological processes. Our gene ontology and pathway analysis study confirms upregulation of immune response, tissue regeneration, wound healing, cell migration, angiogenesis processes, and Jak-Stat, interleukins, inflammatory-induced chemokines and cytokines, notch, and B cell and T cell activation pathways respectively. Based upon expression level changes and their known roles in neuroprotection or stem cell function, we selected 8 candidate genes to explore their potential involvement in different cellular and molecular pathways necessary for brain regeneration. We first confirmed the RNAseq expression changes of the candidates after injury using real-time RT-PCR. Work is ongoing to examine cellular expression changes by in situ hybridization, and to generate loss-of-function models to examine how alterations in the candidate genes influence brain injury and the regenerative process. We are also using the QA excitotoxicity model in mouse striatal lesioning with the goal of comparing gene expression changes with the zebrafish model. Our eventual aim is to shed light on mechanisms underlying the limited regenerative capacity of the mouse brain with the goal of improving brain repair.