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Abstract

BackgroundMechanisms that affect recovery from fetal and neonatal hypoxic-ischemic (H-I) brain injury have not been fully elucidated. The incidence of intrapartum asphyxia is approximately 2.5%, but the occurrence of adverse clinical outcome is much lower. One of the factors which may account for this relatively good outcome is the process of neurogenesis, which has been described in adult animals. We used a neonatal mouse model to assess new cells in the hippocampus after H-I injury.ResultsNeonatal mice underwent permanent unilateral carotid ligation on the seventh postnatal day followed by exposure to 8% hypoxia for 75 minutes. The presence of new cells was determined by bromodeoxyuridine (BrdU) incorporation into cells with sacrifice of the animals at intervals. Brain sections were stained for BrdU in combination with neuronal, glial, endothelial and microglial stains.We found a significant increase in BrdU-positive cells in the neonatal mouse hippocampus in the injured area compared to the non-injured area, most prominent in the dentate gyrus (DG) (154.5 ± 59.6 v. 92.9 ± 32.7 at 3 days after injury; 68.9 ± 23.4 v. 52.4 ± 17.1 at 35 days after injury, p < 0.0011). Among the cells which showed differentiation, those which were stained as either microglial or endothelial cells showed a peak increase at three days after the injury in the DG, injured versus non-injured side (30.5 ± 17.8 v. 2.7 ± 2.6, p < 0.0002). As in the adult animal, neurogenesis was significantly increased in the DG with injury (15.0 ± 4.6 v. 5.2 ± 1.6 at 35 days after injury, p < 0.0002), and this increase was subsequent to the appearance of the other dividing cells. Numbers of new oligodendrocytes were significantly higher in the DG on the non-injured side (7.0 ± 24.2 v. 0.1 ± 0.3, p < 0.0002), suggesting that oligodendrocyte synthesis was reduced in the injured hippocampus.ConclusionThese findings demonstrate that the neonatal animal responds to brain injury with neurogenesis, much like the adult animal. In addition, H-I insult leads to more neurogenesis than hypoxia alone. This process may play a role in the recovery of the neonatal animal from H-I insult, and if so, enhancement of the process may improve recovery.

Pathophysiology of perinatal asphyxia: can we predict and improve individual outcomes?

“…Indeed, increased neurogenesis has been observed in brain regions affected by HI [120, 214, 217, 218], including DG, CA1 [43, 213, 219, 220], subventricular zone (SVZ) [221, 222], neostriatum [223] and neocortex [224, 225]. It has been suggested that new cells produced in SVZ can migrate to the lesioned regions [226–229], attracted by stromal cell-derived migratory signalling.…”

Neuroprotective Mechanism of Lycium barbarum Polysaccharides against Hippocampal-Dependent Spatial Memory Deficits in a Rat Model of Obstructive Sleep Apnea

“…Adult hippocampal neurogenesis is responsible for generating new neurons in the brain and found to be triggered by brain injuries and stress including hypoxia to replace damaged and malfunctioned neurons [ 20 , 21 ]. Neurogenic BrdU-labeled and proliferative PCNA-labeled cells were increased in the mice hippocampus and primary hippocampal cultures following hypoxia or ischemia-induced hippocampal apoptosis, which may involve MAP kinase signaling pathway [ 22 , 23 ]. Also, administration of hydrogen sulfide could restore hypoxia-induced cognitive impairment of mice by enhancing hypoxia-triggered hippocampal neurogenesis [ 24 ].…”

Functional Role of Intracellular Calcium Receptor Inositol 1,4,5-Trisphosphate Type 1 in Rat Hippocampus after Neonatal Anoxia

“…The hippocampus has been the subject of several types of research using different models of oxygen deprivation due to its susceptibility to insults [25]. Post-mortem analysis showed that the damage was almost entirely limited to the CA1 subfield of the hippocampus [26], whereas CA2 and CA3 subfields appear to be more resistant to ischaemic events [27,28].…”