Recruitment of neural precursor cells from circumventricular organs of patients with cerebral ischaemia

AIMS: Adult neurogenesis is well described in the subventricular zone of the lateral ventricle walls and in the subgranular zone of the hippocampal dentate gyrus. However, recent studies indicate that self-renewal of neural stem cells (NSCs) is not restricted to these niches, but that diverse areas of the adult brain are capable of generating new neurones and responding to various pathological alterations. In particular, NSCs have been identified in circumventricular organs (CVOs) of the adult mouse brain.

METHODS: In order to detect possible neural stem or progenitor cells in CVOs of the human brain, we analysed post mortem human brain tissue from patients without neuropathological changes (n = 16) and brains from patients with ischaemic stroke (n = 16).

RESULTS: In all analysed CVOs (area postrema, median eminence, pineal gland and neurohypophysis) we observed cells with expression of early NSC markers, such as GFAP, nestin, vimentin, OLIG2 and PSA-NCAM, with some of them coexpressing Ki67 as a marker of cell proliferation. Importantly, stroke patients displayed an up to fivefold increase with respect to the relative number of Ki67- and OLIG2-expressing cells within their CVOs.

CONCLUSIONS: Our findings are compatible with a scenario where CVOs may serve as a further source of NSCs in the adult human brain and may contribute to neurogenesis and brain plasticity in the context of brain injury.