Increased Neurogenesis in the Dentate Gyrus After Transient Global Ischemia in Gerbils

TLDR

Neurogenesis in the adult rodent dentate gyrus is regulated by NMDA receptors, adrenal steroids, environmental stimuli, and seizures. The study aimed to determine whether transient global ischemia alters neurogenesis in adult gerbils by examining newly divided dentate gyrus cells. Neurogenesis was assessed using 5‑bromo‑2′‑deoxyuridine labeling and immunohistochemistry after 10‑minute bilateral common carotid artery occlusion. A 12‑fold increase in dentate gyrus cell birth 1–2 weeks after ischemia was observed, with BrdU‑positive cells differentiating into mature neurons that persisted for months, a response independent of CA1 loss or entorhinal cortical damage and potentially supporting functional recovery.

Abstract

Neurogenesis in the dentate gyrus of adult rodents is regulated by NMDA receptors, adrenal steroids, environmental stimuli, and seizures. To determine whether ischemia affects neurogenesis, newly divided cells in the dentate gyrus were examined after transient global ischemia in adult gerbils. 5-Bromo-2′-deoxyuridine-5′-monophosphate (BrdU) immunohistochemistry demonstrated a 12-fold increase in cell birth in the dentate subgranular zone 1–2 weeks after 10 min bilateral common carotid artery occlusions. Two minutes of ischemia did not significantly increase BrdU incorporation. Confocal microscopy demonstrated that BrdU immunoreactive cells in the granule cell layer colocalized with neuron-specific markers for neuronal nuclear antigen, microtubule-associated protein-2, and calbindin D 28k , indicating that the newly divided cells migrated from the subgranular zone into the granule cell layer and matured into neurons. Newborn cells with a neuronal phenotype were first seen 26 d after ischemia, survived for at least 7 months, were located only in the granule cell layer, and comprised ∼60% of BrdU-labeled cells in the granule cell layer 6 weeks after ischemia. The increased neurogenesis was not attributable to entorhinal cortical lesions, because no cell loss was detected in this region. Ischemic preconditioning for 2 min, which protects CA1 neurons against subsequent ischemic damage, did not prevent increased neurogenesis in the granule cell layer after a subsequent severe ischemic challenge. Thus, ischemia-induced dentate neurogenesis is not attributable to CA1 neuronal loss. Enhanced neurogenesis in the dentate gyrus may be a compensatory adaptive response to ischemia-associated injury and could promote functional recovery after ischemic hippocampal injury.