The Hippocampal Neuro-Glio-Vascular Network: Metabolic Vulnerability and Potential Neurogenic Regeneration in Disease

Brain metabolism is a fragile balance between nutrient/oxygen supply provided by the blood and neuronal/glial demand. Small perturbations in these parameters are necessary for proper homeostatic functioning and information processing, but can also cause significant damage and cell death if dysregulated. During embryonic and early post-natal development, massive neurogenesis occurs, a process that continues at a limited rate in adulthood in two neurogenic niches, one in the lateral ventricle and the other in the hippocampal dentate gyrus. When metabolic demand does not correspond with supply, which can occur dramatically in the case of hypoxia or ischemia, or more subtly in the case of neuropsychiatric or neurodegenerative disorders, both of these neurogenic niches can respond—either in a beneficial manner, to regenerate damaged or lost tissue, or in a detrimental fashion—creating aberrant synaptic connections. In this review, we focus on the complex relationship that exists between the cerebral vasculature and neurogenesis across development and in disease states including hypoxic-ischemic injury, hypertension, diabetes mellitus, and Alzheimer’s disease. Although there is still much to be elucidated, we are beginning to appreciate how neurogenesis may help or harm the metabolically-injured brain, in the hopes that these insights can be used to tailor novel therapeutics to regenerate damaged tissue after injury.