Effects of a Period of Asphyxia during Birth on Spatial Learning in the Rat

Boksa, Patricia; Krishnamurthy, Anuradha; Brooks, William D.

doi:10.1203/00006450-199504000-00018

Cited by 76 publications

(41 citation statements)

References 17 publications

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“…Control pups are born by rapid Csection alone or vaginally. Using this model, we have demonstrated that, as adults, rats born by C-section with 10 or 15 min of added acute anoxia, show a subtle deficit in acquisition of spatial learning in a Morris water maze [5]. Components of the stress reponse are also affected by birth condition in this model.…”

Section: Introductionmentioning

confidence: 88%

Responses to Stress and Novelty in Adult Rats Born Vaginally, by Cesarean Section or by Cesarean Section with Acute Anoxia

Boksa

Wilson

Rochford³

1998

Neonatology

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The aim of this study was to test the hypothesis that alterations in birth conditions, specifically vaginal birth vs. birth by Cesarean section (C-section) vs. birth by C-section with an added period of acute global anoxia, produces long-term differences in behavioral responses to stress or novelty in the rat at adulthood. In comparison to animals born by rapid C-section alone, animals born by C-section with 10 or 15 min of added anoxia were significantly more immobile during forced swim stress administered for 6 trials over several weeks. In a step-down passive avoidance task, there were no group differences in acquisition or retention of the avoidance response. However, when initially placed in the passive avoidance apparatus before delivery of shock, animals born by C-section with 15 min of anoxia required significantly more pretrials to step down from the wooden platform, than did vaginally born or C-sectioned animals. No group differences were observed on measures of exploratory behavior in an elevated plus-maze or of approach behavior either to food or to a novel object in an open field. These findings suggest that birth conditions which include a degree of perinatal hypoxia can contribute to variability in selective responses to stress and novelty in the adult rat.

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Section: Introductionmentioning

confidence: 88%

Responses to Stress and Novelty in Adult Rats Born Vaginally, by Cesarean Section or by Cesarean Section with Acute Anoxia

Boksa

Wilson

Rochford³

1998

Neonatology

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“…Shortterm effects (8 d after induction of asphyxia) involve delayed cell death in frontal cortex, striatum, and cerebellum (20,21) and increased dopamine levels in mesencephalic and telencephalic regions (19). Long-term changes involve alterations in dopaminergic system (22) and in myelination patterns (23), as well as motor alterations and slight impairments in retention of a spatial learning task (17). The aim of our investigation was to assess the occurrence of biochemical alterations in the brain of asphyctic rat pups shortly after the insult, which could be related to abnormalities in neonatal behavior patterns, with respect to ultrasonic vocalization pattern, spontaneous motor behaviors, and homing response.…”

mentioning

confidence: 99%

“…Due to the different degree of CNS maturity at birth between rodents and humans (15), this asphyxia model relates more to the condition of the premature rather than the term human infant (16). In this model, neural and behavioral alterations have been identified (17)(18)(19)(20). Shortterm effects (8 d after induction of asphyxia) involve delayed cell death in frontal cortex, striatum, and cerebellum (20,21) and increased dopamine levels in mesencephalic and telencephalic regions (19).…”

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confidence: 99%

Increased Brain Levels of F2-Isoprostane Are an Early Marker of Behavioral Sequels in a Rat Model of Global Perinatal Asphyxia

et al. 2004

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Perinatal asphyxia is a major cause of immediate and postponed brain damage in the newborn. It may be responsible for several delayed neurologic disorders and, in this respect, early markers of brain injury would be relevant for therapeutic intervention as well as for identification of infants at high risk for developmental disabilities. Biochemical measurements (brain F 2 -isoprostane levels) and behavioral tests (ultrasonic vocalization pattern on postnatal days (pnd) 5, 8, and 11, spontaneous motor behaviors on pnd 7 and 12, and homing response on pnd 10) were performed in a rat model of global perinatal asphyxia in the immature neonate. Caesarean section was performed in rats and the pups, still in uterus horns, were placed into a water bath at 37°C for either 10 or 20 min. Caesarean delivered pups were used as controls. Pups experiencing severe (20 min), in contrast to those undergoing the 10 min, asphyctic insult presented with detectable abnormalities including early (two hours after the insult) increase in brain F 2 -isoprostane (a direct marker of oxidative injury) without detectable changes in PGE 2 , COX-2 and iNOS levels, and delayed physical (reduced weight gain on pnd 5 and thereafter) and behavioral disturbances (alterations in ultrasound emission on pnd 11 and spontaneous motricity levels mainly). These findings suggest that increased brain F 2 -isoprostane levels shortly after the asphyctic insult are predictive of delayed behavioral disturbances in the newborn rat. The present 20-min asphyxia model might serve for the assessment of preventive and curative strategies to treat neurologic/behavioral disturbances associated with perinatal asphyxia. Perinatal asphyxia is a major cause of neonatal mortality and irreversible damage to the brain. Severe asphyxia may induce major deficits (cerebral palsy, dystonia, epilepsy) shortly after birth (1), while mild/moderate asphyxia episodes may result in cognitive/attentional disorders later on in development. A critical concept emerging from recent research is that of a "therapeutic window." namely a narrow period of time between the insult and the occurrence of CNS injury, during which adoption of neuroprotective strategies could be effective (2, 3). A primary aim for clinical research is to identify as early as possible reliable indexes of brain injury in the asphyctic newborns to apply potential therapeutic interventions at the optimal time and to identify those infants at high risk for developmental delays and disabilities (4).To date the major advances in the early prediction of hypoxic-ischemic insult have been attained by means of EEG and

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“…This parallels reports of increased mild respiratory distress in humans following C-section vs. vaginal birth (Hales et al 1993). It is important to note, however, that adult rats born by the current C-section procedure perform normally in a wide range of behavioral tests (Boksa et al 1995 and, therefore, are not generally impaired. Rats born by C-section ϩ 10 min global anoxia show reduced brain ATP and increased brain lactate at birth, indicative of CNS hypoxia.…”

Section: Possible Mechanisms By Which C-section Birth and Global Anoxmentioning

confidence: 51%

Caesarean Section Birth Produces Long Term Changes in Dopamine D1 Receptors and in Stress-induced Regulation of D3 and D4 Receptors in the Rat Brain

El-Khodor

Boksa

2001

Neuropsychopharmacology

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Effects of a Period of Asphyxia during Birth on Spatial Learning in the Rat

Cited by 76 publications

References 17 publications

Responses to Stress and Novelty in Adult Rats Born Vaginally, by Cesarean Section or by Cesarean Section with Acute Anoxia

Responses to Stress and Novelty in Adult Rats Born Vaginally, by Cesarean Section or by Cesarean Section with Acute Anoxia

Increased Brain Levels of F2-Isoprostane Are an Early Marker of Behavioral Sequels in a Rat Model of Global Perinatal Asphyxia

Caesarean Section Birth Produces Long Term Changes in Dopamine D1 Receptors and in Stress-induced Regulation of D3 and D4 Receptors in the Rat Brain

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