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

By Jialing Liu, Karen Solway, R. Messing, F. Sharp. 1998

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 D28k, 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.

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Citations in the corpus

Subventricular Zone-Derived Neuroblasts Migrate and Differentiate into Mature Neurons in the Post-Stroke Adult Striatum (2006, background): “In the rodent brain, cerebral ischemia enhances neurogenesis in the SVZ and SGZ (Liu et al., 1998; Arvidsson et al., 2001; Jin et al., 2001), and ectopic neurogenesis has been observed in the ipsilateral striatum in animal models of middle cerebral artery occlusion (MCAO) (Arvidsson et al.”
Adult neurogenesis: from precursors to network and physiology. (2005, background): “A peak in cell proliferation occurs 1–2 wk after ischemia, and a quarter of the newly generated cells die during the first month (315).”
Granule-Like Neurons at the Hilar/CA3 Border after Status Epilepticus and Their Synchrony with Area CA3 Pyramidal Cells: Functional Implications of Seizure-Induced Neurogenesis (2000, background): “…et al., 1998a,b), neurotransmitters and hormones (Cameron et al., 1995; Brezun and Dazsuta, 1999; Tanapat et al., 1999), lesions (Gould and Tanapat, 1997), or hypoxia/ischemia (Liu et al., 1998; BossenmeyerPourié et al., 1999) can result in alterations in neurogenesis in the dentate gyrus.”
Milestones of neuronal development in the adult hippocampus. (2004, background): “ischemia [ 5 ], trauma [6] or seizures [7,8]) all have ‘identical’ effects on adult neurogenesis, in that they plainly just induce proliferation of a precursor cell or increase their survival?”
Increased neurogenesis in a model of electroconvulsive therapy. (2000, background): “In rodents, brain insults such as global ischaemia (Liu et al 1998) and experimentally induced seizures markedly increase hippocampal neurogenesis, although primarily following extended periods of seizure or in association with neuronal damage (Bengzon et al 1997; Parent et al 1998).”
Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury (2001, background): “…training, ischemia, seizure, decreased levels of adrenal steroids, NMDA receptor antagonists as well as specific growth and proliferating factors have been reported to increase neurogenesis in the dentate gyrus (Gould, 1994; Cameron et al., 1994, 1995; Parent et al., 1997; Liu et al., 1998).”
The potential of neural stem cells to repair stroke-induced brain damage (2009, background): “Liu et al. [ 68 ] conducted the pioneering study using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry to demonstrate a 12-fold increase in cell birth in the DG at 1–2 weeks after a 10 min global ischemia in adult gerbils.”
Functional neurogenesis in the adult hippocampus (2002, background): “In addition, new neurons are generated in the hippocampus after strok”
Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways (2006, background): “Indeed , acute increases in excitatory input induced by ischemia or seizure activity can also induce prolifera - tion in the DG in vivo ( Liu et al .”