NON-EXHAUSTIVE ACTIVATION OF ADULT HIPPOCAMPAL NEURAL STEM CELLS AND THEIR PROGENY BY CORTICAL SPREADING DEPOLARIZATIONS

Cortical spreading depolarizations (CSD) are waves of neuroglial mass depolarization occurring in acute brain injury. Depending on metabolic context, CSD can either exacerbate tissue damage or promote adaptive plasticity in well-supplied brain regions. We have previously shown that CSD induce a robust increase in adult hippocampal neurogenesis (AHN), a unique form of plasticity in which neurons are generated from adult neural stem cells (aNSCs) and integrate into dentate gyrus circuits. However, whether this neurogenic response is adaptive or maladaptive remains unresolved.
Critically, the long-term consequences of AHN depend on how aNSCs are recruited. Under physiological conditions, aNSCs are maintained in quiescence to preserve their pool, whereas excessive activation, as observed after epileptic seizures, leads to transient neurogenic boosts followed by premature aNSC depletion and long-term impairment of AHN. Whether CSD induce a controlled, adaptive increase in AHN or trigger maladaptive aNSC overactivation has not been directly addressed.
To resolve this, we induced repetitive CSD in Nestin-GFP mice (both sexes, 10–12 weeks old) using hyperosmolar potassium chloride (sodium chloride in controls). BrdU fate mapping combined with confocal immunofluorescence was used to quantify proliferation and population dynamics of individual precursor stages. Our preliminary data show that CSD activate all hippocampal precursor stages, including aNSCs (~2-fold increase in BrdU⁺ aNSCs), without detectable long-term depletion of the aNSC pool or sustained alterations in AHN.
Together, these findings indicate that CSD elicit an adaptive, non-exhaustive activation of the hippocampal neurogenic program, supporting plasticity after brain injury while preserving long-term neurogenic capacity.