Alcohol and the Developing Brain : Autopsy, Neuroanatomical Studies

by National Institute of Health

(Page 2 of 4)

Autopsy Studies

Anatomical changes occurring at the cellular level in humans can best be revealed with autopsy material. Although only a very small number of brains are available for this level of analysis, finding any microscopic changes in the brain lends considerable support to the claim that developmental alcohol exposure induces neuronal injury, which ultimately may be responsible for the behavioral and cognitive changes observed in children exposed to alcohol prenatally.

Clarren and associates found changes in the structure of the autopsied brains of four children diagnosed with FAS. The most prevalent findings in these brains were incorrectly located (ectopic) neurons in the white matter, suggesting errors in the migration of neurons throughout the brain. In one case there was a complete absence of the corpus callosum and anterior commissure, another fiber bundle that connects regions of the brain. Ferrer and Galofre found that the short, hair-like projections (dendritic spines) on fibers called dendrites, which extend from neurons to receive information from other neurons, also were affected. They reported that the brain from a 4-month-old infant with FAS showed a significant decrease in the number of dendritic spines on nerve cells projecting from the cortex to other parts of the brain and spinal cord. Another autopsy case, of a 2-month-old infant born to a mother who binge drank during pregnancy (primarily during the first trimester), revealed absent olfactory bulbs and tracts (which the brain uses to sense odors); poorly developed optic tracts; fused anterior brain structures such as the septum, thalamus, and the head of the caudate nucleus; fewer cells in the dentate gyrus, which is part of the hippocampus (an area crucial for memory); and fewer nerve cells in the cerebellum (which regulates balance, posture, movement, and muscle coordination) known as Purkinje cells, and disorientation of these cells. Although these autopsy data are based on a small number of subjects, they seem to show that prenatal alcohol exposure does have a damaging effect on the structural organization of the developing human brain.

Animal Neuroanatomical Studies

Most of the current information on how developmental exposure to alcohol induces brain damage comes from animal studies. Because of the obvious ethical constraints of performing certain procedures on humans, the retrospective nature of the human data, and numerous confounding variables, human studies cannot address issues that can be addressed with animal studies. Researchers are able to control factors such as dose, timing, and pattern of alcohol exposure in animal studies. And because there are so few human autopsy cases, researchers have performed most neuroanatomical assessments, particularly at the cellular level, on animals. The following sections briefly summarize several hallmark findings related to neuroanatomical studies of the effects of developmental alcohol exposure in animals.

Microencephaly

Microencephaly, defined in animal subjects as having a small brain relative to body size, is a gross neuroanatomical anomaly associated with heavy alcohol exposure during development. As described above, such an anomaly in humans is inferred by deficits in head circumference because we cannot remove and weigh the human brain. However, in animals, the most common and traditional means of measuring microencephaly is brain weight.

Numerous reports have shown that alcohol exposure during the brain growth spurt (a period of most intense brain growth) in rats significantly reduces the weight of the forebrain, brain stem, and cerebellum. Importantly, in the microencephalic brain, not every brain region is affected equally. Using state-of-the-art three-dimensional stereological techniques, researchers can estimate the volume of various brain regions to demonstrate microencephaly. Many of these stereological studies have demonstrated that developmental alcohol exposure leads to reductions both in brain weight and volume in a rat model. It appears that heavy alcohol exposure during the brain growth spurt (early postnatal period in rats, and third trimester and early infancy in humans) leads to the most severe and pronounced microencephaly compared with exposure during other developmental stages. Surprisingly, in rats, even 1 day of alcohol exposure at a high dose is sufficient to cause growth deficits in specific brain regions, such as the cerebellum. Olney and colleagues recently have suggested that these alcohol-induced reductions in brain volume and neuronal loss may be attributed to alcohol-induced neurodegeneration via programmed cell death (apoptosis).

Neuronal Loss

One of the most devastating and extreme consequences of developmental alcohol exposure is the loss of neurons, and the data documenting neuronal loss are derived mostly from animal studies. Although selective programmed neuronal death is a normal aspect of CNS development, excessive neuronal death disrupts the development of normal neural networks and may lead to cognitive and behavioral dysfunctions (in both humans and animals). Distinct regions and specific cell types appear to be affected by alcohol-induced neuronal loss. Studies in rats have clearly demonstrated that alcohol causes a reduction of cerebellar Purkinje cells, cells of the olfactory bulb, and pyramidal cells in a part of the hippocampus known as the CA1 region. In other neuronal populations, however, such as those in the ventrolateral nucleus of the thalamus (an area important for voluntary movement) and the locus coeruleus (a group of nerve cells involved in arousal and vigilance), alcohol does not cause cell loss. This pattern of alcohol-induced loss of neurons is important for two reasons: 1. it establishes a correlation between the severity of neuronal loss of a specific neuronal population and the degree of behavioral deficits associated with such a cell population, and 2. it provides insight into the specific characteristics of neuronal populations that are most vulnerable or most resistant to alcohol-induced neuronal loss.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.