Jean Sands

Comparative aspects of the brain growth spurt

The brain in all species appears to grow through a sigmoid trajectory when its weight is plotted against its age. The transient period of rapid growth illustrated by such a curve is now commonly known as the ‘brain growth spurt’, and we have previously put forward the hypothesis that this may be a period of enhanced vulnerability to nutritional and other growth restriction [ 61. Since the timing of the brain growth spurt is different in relation to birth in different species, this must be one of the major factors to be taken into account when any attempt is made to extrapolate results obtained in one species to any other. It is a particular problem of many kinds of research into the developing human brain that experimental data must be collected from other animals, because it would be both unethical and impracticable to determine the result in human fetuses and babies. (Perhaps it is worth reflecting that difficulties of practicality would be formidable even if there were no ethical problems, due partly to the very long time span of human growth and development as well as to its complexity. Some would also say the human environment was much too complicated to bear analysis compared with that of other ‘lower’ species, but that is an assumption which may be false, at least for the behavioural scientist.) One of the main attractions of the ‘brain growth spurt’ hypothesis of vulnerability to environmental adversity has been that it links the consequences ln the brain to the timing of the adversity in relation to its developmental age; and it specifies that age in terms of the events of brain growth, regardless of species differences in the timing of birth. Indeed a relation to events or stages, rather than to ages, is so clear a feature of most developmental neuropathology, from the earliest embryological period until the construction of the mature system is eventually accomplished, that it might have been thought too obvious to need further emphasis if it were not still so frequently ignored. *The authors gratefully acknowledge the support of the National Fund for Research into Crippling Diseases, and the Medical Research Council.

Growth and development of the brain and spinal cord of the guinea pig

Summary The growth and development of the brain and spinal cord of the guinea pig has been studied from 29 days of foetal life until maturity. An attempt has been made to describe cell multiplication and degree of myelination in quantitative terms by determining the changing levels of certain chemical indices of histological structure. By this means it has been posssible to distinguish separate peak periods of glial multiplication and myelination both of which occur later than the period of fastest growth in wet weight. This method of describing brain development was undertaken as a preliminary step in an investigation of the heightened vulnerability of the growing brain during its periods of fastest growth. The study has also illustrated the precedence taken by the developing brain over the growth of the rest of the body, the loss of brain water as myelination proceeds, and a falling cell density even at a time when the total number of cells is rising. The timing of all these events in relation to birth is in accordance with the precocity of central nervous system development in this species.

Head circumference, biparietal diameter and brain growth in fetal and postnatal life.

The curves for biparietal diameter, head circumference and brain weight with increasing age have different shapes, and these differences have been explained. Interconversion procedures are suggested. One important consequence of changing growth velocities relates to assessing prognosis for catch-up following adversity. On the assumption that catch-up of brain growth must occur within the period of the brain weight growth spurt, the interpretation of head circumference charts is discussed.

CELL NUMBER AND CELL SIZE: ORGAN GROWTH AND DEVELOPMENT AND THE CONTROL OF CATCH-UP GROWTH IN RATS

One of the most important hypotheses for the control of catch-up after nutritional growth restriction relates developmental vulnerability to an early phase of cell multiplication, rather than to a later phase of growth of cell size. A re-examination of growing tissues, however, does not show the expected sequence of growth events, and the former hypothesis is therefore not supported.

A comparison of the effects of cytosine arabinoside and adenine arabinoside on some aspects of brain growth and development in the rat.

1 Treatment of pregnant rats with cytosine arabinoside (ara‐C, 50 mg/kg, i.p.) at 14 days of gestation severely impaired both prenatal and postnatal whole brain growth in their offspring, although the cerebellum was relatively less affected than whole brain. 2 Rats treated at 5 days of age with ara‐C (250 mg/kg, i.p.) showed an impairment in growth of the cerebellum relative to the rest of the brain. 3 Adenine arabinoside (ara‐A) treatment, either prenatally or postnatally, had negligible effect on brain growth, even at doses considerably higher than those of ara‐C. 4 Adult rats, previously treated with ara‐C (50 mg/kg, i.p.) at 14 days of gestation, showed an impairment in discrimination learning when tested in a water T‐maze. 5 These results are discussed in relation to the proposed use of ara‐C or ara‐A as antiviral agents, particularly against intrauterine infection with cytomegalovirus.

Continuing growth and development of the third-trimester human placenta

Two hundred and nineteen human placentae of well ascertained gestational age were measured for weight and nuclear number. Contrary to previous reports, analysis of the results showed no faltering in either parameter, however expressed. The placentae from babies exhibiting intrauterine growth retardation were appropriate to the size of the babies. However else the placenta ages it does not do so in respect of the rate of increase in the number of its nuclei.

Behaviour, brain and body growth of guinea-pigs after prenatal growth restriction.

I . Guinea-pigs were growth-retarded in early life by feeding their mothers a restricted quantity of food during the second half of pregnancy. After birth, all animals were fed ad Iib. Body-weights were recorded weekly and behavioural tests were made on adult males. The animals were then killed and their brains dissected into forebrain, cerebellum and brain stem. These regions were weighed and DNA-phorphorus content measured. 2. At 14 weeks each male was paired with another male for 10 min on four consecutive days and their social behaviour scored. Tests I and 2 were on like-treatment pairs and tests 3 and 4 on unlike-treatment pairs. At 25 weeks the same animals were subjected to six graded series of brief, unavoidable shocks and their responses recorded. After 3 d, thresholds of aversion to electric shock were measured by recording the period of time spent on the ‘safe’ side of a rectangular box at five shock levels. 3. Undernourished guinea-pigs were significantly lighter than controls at birth but not at adulthood. Regional brain weights and DNA-P content of previously-undernourished guinea-pigs were significantly lower than those of controls, with the greatest deficit in brain stem. 4. Pairs of previously-undernourished guinea-pigs began to interact more quickly and threatened and nosed each other more often than pairs of controls. In mixed pairs previously-undernourished animals chased controls more than their control partners chased them. There were no differences between groups in responsiveness to unavoidable shock or in aversion thresholds.