[Course and neurological/behavioral development of preterm children]. / Parcours et développement neurologique et comportemental de l'enfant prématuré

Preterm birth remains a public health priority given that one child out of ten is born before 37 weeks of gestation. Survival without major neonatal morbidity has increased in high-income countries, in particular in France and in cases of extreme preterm birth before 27 weeks of gestation. Rate of severe handicaps, such as cerebral palsy, is probably decreasing, but specific cognitive disabilities in a variety of domains remain frequent, interfering with normal learning abilities at school and explaining the high rate of special education needs. Prevalence of sequelae increases when gestational age at birth decreases. However, because there are more moderate to late preterm children compared to very preterm children, the absolute number of children with specific cognitive or neurological disabilities is equivalent in these two groups. Better characterization of the development in a recent cohort of very preterm children is necessary to improve the early detection of variations in normal neurodevelopment and to propose trials with remediation actions targeting working memory and language for example. These protocols could decrease the rates of learning disabilities at school.

Prenatal exposure to ethinylestradiol elicits behavioral abnormalities in the rat.

Pregnant rats were i.p. injected with a solution of 17alpha-ethinylestradiol (15 microg kg(-1)) every day between day 9 and day 14 of pregnancy and the behavior of the offspring was compared to that of rats born from dams injected with the vehicle only during the same gestational period. The percentage of neonatal death was dramatically high in the prenatally treated group. Growth of the surviving animals was even better than that of controls, but when adult, they exhibited a number of behavioral abnormalities: increased spontaneous motor activity, decreased exploratory behavior, impaired cognitive processing, qualitatively different exploratory drive, and/or persevering behavior, increased anxiety-like behavior and social neophobia. These behavioral alterations, which resemble a number of psychiatric syndromes, suggest that ethinylestradiol altered the ontogenesis of different parts of the central nervous system involved in cognitive and emotional processes. However, it cannot be excluded that the changes in behavior of ethinylestradiol exposed offspring were due to the abnormal maternal behavior of the estradiol treated dams.

Chronic stress in pregnant rats: effects on growth rate, anxiety and memory capabilities of the offspring.

Female rats were repeatedly stressed for 10 periods of 15 min by the presence of a cat, at the 10th (S10) or the 19th (S19) gestational day. The litter from stressed females often contained a majority of males or a majority of females, especially in the S19 group. The death of pups was dramatically high in the S19 group and, compared with controls, growth of the surviving animals was slower. When adult, their long-term memory was altered and they exhibited an aversive behavior relative to wide areas. Moreover, cognitive alterations were revealed by the low level of exploration and the inability to rapidly process the relevant environmental cues. These deficits resemble those of psychiatric patients who had been submitted to pre-natal stress.

An animal model of autism: behavioural studies in the GS guinea-pig.

Autism is a human behavioural pathology marked by major difficulties in abnormal socialization, language comprehension and stereotypic motor patterns. These behavioural abnormalities have been associated with corticocerebral and cerebellar abnormalities in autistic patients, particularly in vermal folia VI and VII. Progress in understanding this disease has been hindered by the absence of a non-primate animal model. GS guinea-pigs are a partially inbred, non-ataxic guinea-pig strain with cerebellar and corticocerebral abnormalities similar to those reported to exist in human patients with autism. In order to determine if GS guinea-pigs represent an animal model of autism, their behaviour was compared with that of Hartley strain guinea-pigs. GS animals learned a motor task significantly more rapidly than Hartley guinea-pigs, but performed it in a more stereotypic manner and were less influenced by environmental stimuli than Hartleys. GS animals exhibited significantly less exploratory behaviour in a novel environment and were significantly less responsive to 50-95 dBA pure tones than Hartley guinea-pigs. In a social interaction assay, GS guinea-pigs interacted significantly less frequently with each other or with Hartley guinea-pigs than Hartleys did under the same conditions. GS behaviour thus exhibits autistic-like behaviour patterns: motor stereotypy, lack of exploration and response to environment and poor social interaction. Coupled with the neuropathological findings, this abnormal behaviour suggests that GS guinea-pigs could be a useful animal model of autism.

Timed active avoidance learning in lurcher mutant mice.

Lurcher mutant mice (+/Lc) which exhibit a massive loss of neurons in the cerebellar cortex and in the inferior olivary nuclei were subjected to an active avoidance learning task; the animals' avoidance response must occur within a small time window after a short or a long delay. The control mice needed a mean of 8.3 sessions of 10 trials (short delay group) and of 11.8 sessions (long delay group) and showed good retention after a 24 h interval. When subjected to the same number of sessions, the +/Lc mice were unable to learn the timing task. However, a subgroup of lurcher mutants was able to learn after a high number of sessions (25.4 sessions as a mean). There was no intergroup difference in the standard version of one-way active avoidance. These results indicate that the cerebellar cortex is involved in time processing during active avoidance. The cerebellum may be part of a loop including the cerebral cortex known to be involved in time perception. An alternative explanation is that the cerebellar mutant animals had persevering tendencies acquired during performance of the one-way avoidance task.

Acute stress in pregnant rats: effects on growth rate, learning, and memory capabilities of the offspring.

Growth rate of the offspring of female rats stressed by the presence of a cat at the 10th or the 19th gestational day was lower than that of controls whereas footshocks administered at the same periods did not significantly influence growth rate of the young. Whatever the nature of the stress and the time when it was administered to the mother, the death rate of the young rats was much greater than that in controls. When adult, the offspring of stressed mothers exhibited learning and memory impairments in a delayed alternation task as well as in passive avoidance conditioning. Alteration of these cognitive functions is interpreted in terms of subtle dysfunctions in the development of the nervous system through modifications of the hormonal components of the mothers, particularly eventual alterations of the nervous system biochemistry of the offspring.

Influence of olfactory stimulation on nociceptive behavior in mice.

The reactions elicited by nociceptive stimulations were studied in mice exposed to the presence of different odors: positive (attractive), negative (aversive), or neutral. In a first set of experiments, the animals were not habituated to the odors before the nociceptive stimuli were applied; in this case, the olfactory environment during experienced pain had essentially no effect on the nociceptive reactions, whatever the nature of the odors. In a second set of experiments, the animals were habituated to the same odor for 20 days. The control group consisted of mice habituated to and tested in the presence of the odor of the laboratory. In that case, compared to controls, the neutral odor had no influence on nociceptive reactions. By contrast, the positive odor decreased and the negative odor increased the reactions, especially when the intensity of the nociceptive stimulus was low. Moreover, it has been shown that the reactions elicited during a second nociceptive stimulation period depend on the perception of pain animals experience during the first stimulation, which depended, in turn, on the odor associated with it. Results are discussed in terms of opioid-mediated interactions between olfaction and pain.