It is not the intent of this chapter to provide a comprehensive documentation of all the changes that have been recorded in the cells of the central nervous system as they age. Rather, we have chosen to follow the rather narrow path of using our own studies of the pyramidal neurons and neuroglial cells in the primary auditory cortex (area 41) of the aging rat as a basis for the following account, and to refer to recent studies of our own colleagues and of other investigators as appropriate within that context. This approach is bound to result in a rather biased description of the aging of neurons and neuroglia, but we believe that sufficient information will be given in this account for the reader to use it as a means of gaining access to studies that provide additional information and other views.

Central Nervous System

Image analysis apparatus was used to count and measure glial and neuronal perikarya in ten size classes in the midfrontal region and superior temporal gyrus of 18 patients with senile dementia of the Alzheimer type for comparison with 12 age-matched normal specimens. Brain weight was about 8% less in the dementia group. The major differences had to do with larger neurons, which in dementia were reduced by about 40% in the frontal cortex and 46% in the temporal region. The concentration of neuritic plaques did not correlate significantly with brain weight, cortical thickness, or cell counts.

Some morphometric aspects of the brain in senile dementia of the Alzheimer type.

Neuron numbers and dendritic extent in normal aging and Alzheimer's disease

For half a century, the human brain was believed to contain about 100 billion neurons and one trillion glial cells, with a glia:neuron ratio of 10:1. A new counting method, the isotropic fractionator, has challenged the notion that glia outnumber neurons and revived a question that was widely thought to have been resolved. The recently validated isotropic fractionator demonstrates a glia:neuron ratio of less than 1:1 and a total number of less than 100 billion glial cells in the human brain. A survey of original evidence shows that histological data always supported a 1:1 ratio of glia to neurons in the entire human brain, and a range of 40-130 billion glial cells. We review how the claim of one trillion glial cells originated, was perpetuated, and eventually refuted. We compile how numbers of neurons and glial cells in the adult human brain were reported and we examine the reasons for an erroneous consensus about the relative abundance of glial cells in human brains that persisted for half a century. Our review includes a brief history of cell counting in human brains, types of counting methods that were and are employed, ranges of previous estimates, and the current status of knowledge about the number of cells. We also discuss implications and consequences of the new insights into true numbers of glial cells in the human brain, and the promise and potential impact of the newly validated isotropic fractionator for reliable quantification of glia and neurons in neurological and psychiatric diseases. J. Comp. Neurol. 524:3865-3895, 2016. © 2016 Wiley Periodicals, Inc.

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The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting.

Fifty-one brains from clinically and neuropathologically normal individuals ranging in age from 24 to 100 years were studied to determine what changes occur in neocortical neuroectodermal cell populations as a function of normal aging. Twenty-m-thick sections from the midfrontal, superior temporal, and inferior parietal areas were examined with an image-analysis apparatus with combined manual and automatic editing capacity. Neuroectodermal cells were counted, measured, and assigned to one of ten categories, which were later summarized in three: large neurons (<90 m2), small neurons (41 to 90 m2), and glia (5 to 40 m2). Determinations were also made of brain weight, cortical thickness, neuronal density, neuron--glia ratio, and percentage of cell area. The results showed statistically significant age-related decrements in the following values: brain weight, cortical thickness in the midfrontal and superior temporal areas, large neurons in all three areas, and the neuron--glia ratio in the midfrontal and inferior parietal areas. The total number of neurons, neuronal density, and percentage of cell area were all unchanged. Increasing with age were the number of small neurons in the midfrontal cortex and glia in the midfrontal and superior temporal areas. The following conclusions were drawn: (1) Aging affects the frontal and temporal lobes more than the parietal; the salient change is shrinkage of large neurons with consequently increasing numbers of small neurons; (2) constant neuronal density coupled with diminished cortical volume (decreased brain weight and cortical thinning) indicate that there is some neuronal loss with age, but it is of much lesser magnitude than previously supposed; and (3) the number of glia increases with age.

Neocortical cell counts in normal human adult aging.

Volume of the ventral cochlear nucleus in man: its relationship to neuronal population and age.

THE deterioration of mental function in old age may be due to loss of neurones or decay of their function. Several studies support the former view1,2 but sample sizes and the number of cases reviewed were small. Accordingly we studied the ventral cochlear nucleus (VCN) because it is well defined and small enough to make accurate counts feasible.

Neuronal populations in the human brain.

The unique pathological findings of a case of congenital familial hyperbilirubinemia are presented. The patient (Case 3 of Crigler and Najjar9s original report), although severely jaundiced, had developed normally without evidence of neurological disease until 15½ years of age. He then developed a progressive neurological deterioration which was clinically similar to infantile kernicterus. At autopsy most of his organs showed extensive intra- and extracellular deposition of bile pigment, particularly the renal papillae, atrial endocardium, intestinal mucosa, Kupffer cells of the liver, and the perivascular adventitia. Although no pigment was found in the central nervous system, there was striking neuronal loss and gliosis of the thalamus. Moderate neuronal loss was found in the putamen, caudate nucleus, dentate nucleus, and red nuclei. No histopathological changes were found in the hippocampus or cerebral cortex. It is suggested that the patient suffered from a late onset of "kernicterus" with involvement, in this older patient, of regions of the nervous system somewhat different from those in infantile kernicterus.

Familial nonhemolytic jaundice: bilirubinosis and encephalopathy

Hereditary childhood hearing loss andintegumentary system disease

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0022215100072145

Bruce W. Konigsmark

Papers

Volume of the ventral cochlear nucleus in man: its relationship to neuronal population and age.

Neuronal populations in the human brain.

Familial nonhemolytic jaundice: bilirubinosis and encephalopathy

Hereditary childhood hearing loss andintegumentary system disease

Familial congenital moderate neural hearing loss