Neonatal anoxia induces transitory hyperactivity, permanent spatial memory deficits and CA1 cell density reduction in developing rats

Dell'Anna, M. E.; Calzolari, Stefano; Molinari, Marco; Iuvone, Laura; Calimici, R.

doi:10.1016/s0166-4328(05)80078-6

Cited by 119 publications

(63 citation statements)

References 27 publications

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“…Open-field studies revealed a hyperactive behavior in asphyxiated/hypoxic/anoxic rats. Hershkowitz et al [3] demonstrated that after postnatal anoxia, 3-week-old rats displayed hyperactivity, a finding which was confirmed by results of the studies performed by Speiser et al [4], Dell'Anna et al [5], as well as Iuvone et al [6]. al.…”

Section: Introductionmentioning

confidence: 76%

Long-Term Influence of Perinatal Asphyxia on the Social Behavior in Aging Rats

Weitzdoerfer

Gerstl²,

Pollak³

et al. 2004

Gerontology

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Background: Various groups have been addressing the question of whether perinatal asphyxia (PA) affects the behavior of young animals, but no information is available on long-term effects of PA on the behavior in aged rats, although it has been postulated that PA may lead to neurological and psychiatric deficits in adult life. Objective: We, therefore, decided to study the effects of PA on social and anxiety-related behaviors in 2-year-old rats, using a noninvasive animal model resembling the clinical situation. Methods: For the behavioral studies, the open-field test, the elevated plus-maze test, and a social interaction test in pairs were performed. Magnetic resonance imaging of the brain was selected to rule out neuropathological changes due to the aging process per se, as well as asphyxia-induced pathologies in the brain areas known to play an important role in the modulation of behavior. Results: The social interaction test revealed a statistically significant increase in the number of social grooming episodes and the time spent running alone, whereas the numbers of social sniffing and fighting episodes and the time spent running together were decreased in the asphyxiated group. The elevated plus- maze test revealed a higher presence of entries into the closed arm. Furthermore, sniffing and self-grooming episodes were significantly increased in the asphyxiated group. Conclusions: We found a significantly decreased social aggressiveness and an increased social contact behavior as well as increased anxiety levels in the asphyxiated animals. The present findings may provide important information on the long-term behavioral sequelae of PA in the aged individual.

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Section: Introductionmentioning

confidence: 76%

Long-Term Influence of Perinatal Asphyxia on the Social Behavior in Aging Rats

Weitzdoerfer

Gerstl²,

Pollak³

et al. 2004

Gerontology

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“…As for the third "neonatal asphyxia" model, there are reports of a transient hyperactivity in the open field (peaking immediately after weaning), impaired spatialmemory performance, and significant deficits in tests for passive-and active-avoidance (Hershkowitz et al 1983;Speiser et al 1983Speiser et al , 1988. Spatial-memory abilities in the Morris water maze appeared to be reduced both during adolescence and at adulthood (Dell'Anna et al 1991;Iuvone et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Social withdrawal, neophobia, and stereotyped behavior in developing rats exposed to neonatal asphyxia

et al. 2004

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Perinatal asphyxia is a concern for public health and may promote subtle neuropsychiatric disorders. Anoxic insults to neonatal rats cause long-lasting neurobehavioral deficits. In the present study, we focussed on changes in emotional behaviors as a consequence of neonatal asphyxia in Wistar rats. Newborn pups (24 h after birth) underwent a single 30-min exposure to a 100% N2 atmosphere (or air). The offspring was tested for a) locomotor and exploratory activity with or without a d-amphetamine challenge (0, 1, or 2 mg/kg) on postnatal day (pnd) 15; b) social interactions and novelty seeking during adolescence; c) levels of the brain-derived neurotrophic factor (BDNF). In the open-field test (pnd 15), N2-exposed pups injected with the high (2 mg/kg) amphetamine dose exhibited reduced levels of locomotor hyperactivity, and a more marked involvement in stereotyped behaviors. Individual differences emerged in the locomotor response to the novelty-seeking test: two subgroups of rats (separated on the basis of the median value) showed either arousal/attraction or avoidance/inhibition in response to free-choice novelty. The N2-exposed group showed a more marked novelty-induced avoidance and inhibition. Time devoted to allogrooming and play-soliciting behaviors was reduced, whereas object exploration was increased. Levels of BDNF were reduced in the striatum of N2-exposed rats, suggesting poorer synaptic performance of dopamine pathways. In conclusion, these findings suggest an increased risk of developing social withdrawal, neophobia and behavioral stereotypies (common symptoms found in schizophrenia and autism) as a consequence of neonatal asphyxia in preterm humans.

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“…We therefore tested the hypothesis that exposure to transient neonatal hypoxia may secondarily induce neurogenesis in the rat brain. For this purpose, rat pups were exposed to a 20-min episode of oxygen deprivation within 24 h after birth, a treatment thought to mimic birth asphyxia (29,30). The temporal effects of hypoxia were characterized in the CA1 hippocampus, a brain region known to be exquisitely sensitive to oxygen delivery (31), and potential neurogenesis was monitored by the DNA incorporation of the thymidine analogue, BrdU.…”

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confidence: 99%

Neonatal Hypoxia Triggers Transient Apoptosis Followed by Neurogenesis in the Rat CA1 Hippocampus

et al. 2004

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Continuous generation of new neurons has been demonstrated in the adult mammalian brain, and this process was shown to be stimulated by various pathologic conditions, including cerebral ischemia. Because brain oxygen deprivation is particularly frequent in neonates and represents the primary event of asphyxia, we analyzed long-term consequences of transient hypoxia in the newborn rat. Within 24 h after birth, animals were exposed to 100% N 2 for 20 min at 36°C, and temporal changes in the vulnerable CA1 hippocampus were monitored. Cell density measurements revealed delayed cell death in the pyramidal cell layer reflecting apoptosis, as shown by characteristic nuclear morphology and expression levels of Bcl-2, Bax, and caspase-3. Neuronal loss was confirmed by reduced density of neuron-specific enolase (NSE)-labeled cells, and peaked by 1 wk post insult, to reach 27% of total cells. A gradual recovery then occurred, and no significant difference in cell density could be detected between controls and hypoxic rats at postnatal d 21. Repeated injections of bromodeoxyuridine (50 mg/kg) showed that newly divided cells expressing neuronal markers increased by 225% in the germinative subventricular zone, and they tended to migrate along the posterior periventricle toward the hippocampus. Therefore, transient hypoxia in the newborn rat triggered apoptosis in the CA1 hippocampus followed by increased neurogenesis and apparent anatomical recovery, suggesting that the developing brain may have a high capacity for self-repair. (Pediatr Res 55: 561-567, 2004) Abbreviations BrdU, bromodeoxyuridine CO, cytochrome oxidase DAPI, 4,6-diamidino-2-phenylindole DG, dentate gyrus NSE, neuron-specific enolase SVZ, subventricular zone Transient reduction of oxygen supply to the brain is a common feature of the perinatal period, and remains a major cause of neurologic damage (1-3). Depending on the characteristics of the initial insult, consequences may vary from restricted neuronal loss to extensive brain infarction, reflecting the participation of an apoptotic-necrotic continuum (4 -7). In this respect, hypoxic insults have been associated with delayed selective neuronal apoptosis that involves the active participation of specific gene products (8 -12).The brain response to oxygen deprivation appears as a balance between the activation of neurodestructive components and endogenous protective mechanisms (5, 10). Among the various adaptative responses of the brain to severe injury, it has been recently reported that new neurons can be generated through the proliferation of progenitor cells, and thus might help to repair the damaged CNS (13,14). Several studies have documented that experimental ischemia in the adult brain can trigger neurogenesis as a compensatory mechanism to neural cell death (15)(16)(17)(18)(19). Indeed, it is now clearly established that continuous generation of new neurons occurs in the adult mammalian brain (20,21). Newborn cells originate from specific germinative zones, namely the SVZ surrounding the lateral ventr...

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Neonatal anoxia induces transitory hyperactivity, permanent spatial memory deficits and CA1 cell density reduction in developing rats

Cited by 119 publications

References 27 publications

Long-Term Influence of Perinatal Asphyxia on the Social Behavior in Aging Rats

Long-Term Influence of Perinatal Asphyxia on the Social Behavior in Aging Rats

Social withdrawal, neophobia, and stereotyped behavior in developing rats exposed to neonatal asphyxia

Neonatal Hypoxia Triggers Transient Apoptosis Followed by Neurogenesis in the Rat CA1 Hippocampus

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