Bioluminescence imaging visualizes osteopontin-induced neurogenesis and neuroblast migration in the mouse brain after stroke

Rebecca Rogall, Monika Rabenstein, Sabine Vay, Annika Bach, Anton Pikhovych, Johannes Baermann, Mathias Hoehn, Sébastien Couillard-Despres, Gereon Rudolf Fink, Michael Schroeter, Maria Adele Rueger

Osteopontin (OPN), an acidic phosphoglycoprotein, is upregulated in the brain after cerebral ischemia. We previously reported that OPN supports migration, survival, and proliferation of neural stem cells (NSC) in primary cell culture, as well as their differentiation into neurons. We here analyzed the effects of OPN on neuroblasts in vivo in the context of cerebral ischemia. Transgenic mice expressing luciferase under the control of the neuroblast-specific doublecortin (DCX)-promoter, allowing visualization of neuroblasts in vivo using bioluminescence imaging (BLI), were injected with OPN intracerebroventricularly while control mice were injected with vehicle buffer. To assess the effects of OPN after ischemia, additional mice were subjected to photothrombosis and injected with either OPN or vehicle. OPN enhanced the migration of neuroblasts both in the healthy brain and after ischemia, as quantified by BLI in vivo. Moreover, the number of neural progenitors was increased following OPN treatment, with the maximum effect on the second day after OPN injection into the healthy brain, and 14 days after OPN injection following ischemia. After ischemia, OPN quantitatively promoted the endogenous, ischemia-induced neuroblast expansion, and additionally recruited progenitors from the contralateral hemisphere. Our results strongly suggest that OPN constitutes a promising substance for the targeted activation of neurogenesis in ischemic stroke.