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Summary: The Rice-Vannucci model in rodent pups is subject to substantial loss of animals, result inconsistency, and high lab-to-lab variability in extent and composition of induced injury. This protocol allows for highly predictable and reproducible hypoxic-ischemic cerebral injury lesions in post-natal day 10 Wistar rat pups with no mortality. We describe steps for common carotid artery ligation, brief post-operative normothermia, exposure to hypoxia, and post-hypoxic normothermia. Precise timing and temperature control in each step are crucial for a successful procedure.For complete details on the use and execution of this protocol, please refer to Hartman et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

It is hoped that stem cell biology will play a major role in the treatment of a number of so far incurable diseases via transplantation therapy. Today, we know that neural stem cell grafts not only represent a valuable source of missing cells and molecules for the host nervous system, but they also bring with them biological principles and processes assuring tissue plasticity and homeostasis found in early development and in postnatal neurogenic areas. In this review, we discuss the potential of grafted neural stem/progenitor cells to induce plasticity in the adult diseased brain by mimicking the cellular and molecular processes governing the biology of endogenous stem cell niches. If confirmed, such anlagen of “auxiliary niches” could help us to optimize intercellular communication in donor cell-initiated networks of graft–host interactions and to “rejuvenate” the adult nervous system in its response to disease and injury.

In this review we trace back the history of an idea that takes a new approach in restorative neurotransplantation by focusing on the “multifaceted dialogue” between graft and host and assigns a central role to graft-evoked host plasticity. In several experimental examples ranging from the transfer of solid fetal tissue grafts into mechanical cortical injuries to deposits of neural stem cells into hemisectioned spinal cord, MPTP-damaged substantia nigra or mutant cerebella supportive evidence is provided for the hypothesis, that in many CNS disorders regeneration of the host CNS can be achieved by taking advantage of the inherent capacity of neural grafts to induce protective and restorative mechanisms within the host. This principle might once allow us to spare even complex circuitry from neurodegeneration.