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

Abstract

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.

Dl-3-n-Butylphthalide Reduces Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion Through GDNF/GFRα1/Ret Signaling Preventing Hippocampal Neuron Apoptosis

“…Compared to the sham rats, the number of CD34 positive cells were increased in the cortex of CCH 8w and NBP-treated groups, indicating that angiogenesis occurred with effect of NBP, and at a later time point in CCH. Further, the number of CD34 positive cells was the same in the three groups and hippocampal CBF completely recovered to the pre-operative levels, the hippocampus is largely supplied by the posterior cerebral artery, and receives only a minor contribution from the anterior choroidal artery from the internal carotid artery (Kirschen et al, 2018). In addition, thickened vertebral arteries may provide a better blood supply (Xiong et al, 2017; Li et al, 2019).…”

Photobiomodulation for Alzheimer’s Disease: Has the Light Dawned?

“…The paradigm shift regarding the nature of NSCs and the potential of the post-natal brain to regenerate opened the gates for new studies with a new outlook [110]. Now the scientific community is engaged in not only in depth understanding of the adult brain neurogenesis and NSC functions but also how they may be encouraged with novel treatment modalities [111]. Experimentally NSCs/NPs are detected by the incorporation of bromodeoxyuridine (BrdU) into the nuclei of dividing cells after infection into the animal at various times before sacrifice, that can be subsequently measured by an antibody [112].…”

Increased occurrence of pathological mitochondria in astrocytic perivascular endfoot processes and neurons of idiopathic intracranial hypertension

“…Mitochondria plays an imperative role in balancing energy demand and cell death in the brain (Kirschen et al, 2018). To the best of our knowledge, there are currently no reports on mitochondrial health in astrocyte endfeet in IIH.…”

“…To support the complex functions and signaling patterns of endfeet, the endfeet would need well‐functioning mitochondria. Mitochondria plays an imperative role in balancing energy demand and cell death in the brain (Kirschen et al., 2018). To the best of our knowledge, there are currently no reports on mitochondrial health in astrocyte endfeet in IIH.…”