Total Number Of Neocortical Neurons Research Articles

Neocortical Development in Brain of Young Children-A Stereological Study.

The early postnatal development of neuron and glia numbers is poorly documented in human brain. Therefore we estimated using design-based stereological methods the regional volumes of neocortex and the numbers of neocortical neurons and glial cells for 10 children (4 girls and 6 boys), ranging from neonate to 3 years of age. The 10 infants had a mean of 20.7 × 109 neocortical neurons (range 18.0-24.8 × 109) estimated with a coefficient of variation (CV) = 0.11; this range is similar to adult neuron numbers. The glia populations were 10.5 × 109 oligodendrocytes (range 5.0-16.0 × 109; CV = 0.40); 5.3 × 109 astrocytes (range 2.7-8.3 × 109, CV = 0.39); and 0.32 × 109 microglia (range 0.15-0.43 × 109, CV = 0.31). Thus, the estimated mean composite number of neocortical neuron and glial cells was 36.8 × 109 (range26.8-48.3 × 109, CV = 0.21), of which approximately one-half were glial cells. There was a significant linear increase in oligodendrocyte and astrocyte numbers during the first 3 years of life, but no change in the total number of neurons. This is in line with our expectation that the total number of neocortical neurons is already determined in mid-fetal life.

Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain. A possible new animal model of autism

The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20mg/kg or 100mg/kg) continuously during the last 9–12 days of pregnancy and during the lactation period until sacrifice on the 23rd postnatal day. Total number of neocortical neurons was estimated using the optical fractionator and frontal cortical thicknesses were sampled in VPA exposed pups compared with an unexposed control group. We found that pups exposed to 20mg/kg and 100mg/kg doses of VPA had statistically significant higher total number of neurons in neocortex by 15.8% and 12.3%, respectively (p<0.05) compared to controls amounting to 15.5×106 neocortical neurons (p<0.01). There was no statistical difference between the two VPA groups. Pups exposed to100mg/kg, but not to 20mg/kg VPA displayed a significant (p<0.05) broader (7.5%) of frontal cortical thickness compared to controls. Our results support the hypothesis that fetal exposure of VPA may interfere with normal brain development by disturbing neocortical organization, resulting in overgrowth of frontal lobes and increased neuronal cell numbers. The results indirectly suggest that prenatal VPA may contribute as a causative factor in the brain developmental disturbances equivalent to those seen in human autism spectrum disorders. We therefore suggest that this version of the VPA model may provide a translational model of autism.

Effect of age on neocortical brain cells in 90+ year old human females—a cell counting study

An increasing number of people are living past the age of 100 years, but little is known about what differentiates centenarians from the rest of the population. In this study, brains from female subjects in 3 different age groups, 65–75 years (n = 8), 76–85 years (n = 8), and 94–105 years (n = 7), were examined to estimate the total number of neocortical neurons, astrocytes, oligodendrocytes, and microglia. There was no statistically significant difference in the mean number of neocortical neurons between the 3 groups: 17.9 × 109 (CV = SD/mean = 0.15) in the youngest group, 18.1 × 109 (CV = 0.22) in the second group, and 16.32 × 109 (CV = 0.24) in the oldest group. However, there was a significant difference in the total number of neocortical glial cells between the youngest (41.0 × 109) and oldest (29.0 × 109) age groups (p = 0.013). The significance was probably driven by a significant difference in the total number of neocortical oligodendrocytes that differed significantly between the youngest (27.5 × 109) and oldest (18.1. × 109, p = 0.006) age groups. In conclusion, very old individuals have brain neuron numbers comparable with younger individuals, which may be encouraging for those who live into the “fourth age” and may contribute to the longevity of this exceptional group of people.

Neocortical glial cell numbers in human brains

Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18–93 years, 18 females (average age 65 years, range 18–93) and 13 males (average age 57 years, range 19–87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex.

Total neocortical cell number in the mysticete brain

The cetacean brain has long been of scientific interest, not only because of its large size - the largest in the animal kingdom - but also because of its high gyrification. It shows several adaptations to the aquatic environment, especially in the cortical arrangements of functional areas. To study structural aspects of the mysticete brain we estimated neocortical features in the common minke whale using stereological methods. The neocortex was surprisingly thick, equal to that in humans. The total neocortical neuron number was 12.8 x 10(9), and the total neocortical glia number 98.2 x 10(9). Total cell numbers in the auditory and visual cortex were also estimated, and showed that the auditory cortex contained more cells than the visual cortex. In this small sample, no sexual dimorphism was seen within the neocortex of the common minke whale. Our aim was to estimate the total cell number, cortical volume and cell density in the entire mysticete neocortex and compare the total cell number in the auditory cortex with that of the visual cortex using stereological methods. Here, we used the common minke whale as a model of all mysticetes. We wanted to compare these neocortical features to those of other mammals to forward understanding of the evolution of the mammalian brain.

The postnatal development of neocortical neurons and glial cells in the Göttingen minipig and the domestic pig brain

The first mathematically unbiased estimates of neocortical cell numbers are presented from the developing pig brain, including a full description of tissue processing and optimal sampling for application of the stereological optical fractionator method in this species. The postnatal development of neocortical neurons and glial cells from the experimental Göttingen minipig was compared with the postnatal development of neocortical neurons in the domestic pig. A significant postnatal development was observed in the Göttingen minipig brain for both neuronal (28%; P=0.01) and glial cells (87%; P<0.01). A corresponding postnatal development of neurons was not detected in the domestic pig brain. The reason for this strain difference is not known. The mean total number of neocortical neurons is 324 million in the adult Göttingen minipig compared with 432 million in the domestic pig. The glial-to-neuron cell ratio is around 2.2 in the adult Göttingen minipig. Based on these results, the domestic pig seems to be a more suitable model for evaluating the effects of developmental insults on human brain growth and neuronal development than the Göttingen minipig.

Total number of cells in the human newborn telencephalic wall

The total cell numbers were estimated in the neocortical part of the human telencephalon in 10 normal brains of newborn babies within four major developmental zones: the cortical plate/marginal zone, the subplate, the intermediate zone and the ventricular/subventricular zone. Furthermore, the total number of neuron and glial cells was estimated in the cortical plate. The gestational ages ranged from 38+0–42+5 weeks+days of gestation. The mean total cell number was 32.6×10 9 (coefficient of error=0.04) and the total number of neurons in the cortical plate 19.8×10 9 (coefficient of error=0.06). This indicates that the total number of neocortical neurons equals the total number in the adults, which, however, is not the case for the glial cells.

Parcellation and Area-Area Connectivity as a Function of Neocortex Size

Via the accumulation of data from across the neuroanatomy literature, we estimate the manner in which (i) the number of neocortical areas varies with neocortex size, and (ii) the number of area-area connections varies with neocortex size. Concerning parcellation, we find that the number of areas scales approximately as the 1/3 power of gray matter volume, or, equivalently, as the square root of the total number of neocortical neurons. A consequence of this is that the average number of neurons per area also scales approximately as the square root of the total number of areas. Concerning area-area connectivity, we find evidence that the total number of area-area connections scales as the square of the number of areas. These scaling results help constrain theories about the principles underlying neocortical organization.

A volumetric screening procedure for the Göttingen minipig brain

A screening procedure was developed to provide quantitative estimates of structural parameters, regional volumes and neuron number, in a neurotoxicologic study of the Göttingen minipig brain. The study material consisted of normal controls and brains collected from young minipigs which had been exposed in utero to the mitotic inhibitor methylazoxymethanol acetate (MAM). Based on stereological principles and systematic sampling techniques, volumetric data from pre-selected regions of the pig brain was obtained using Cavalieri's principles and point-counting. Secondarily, estimates of total hemispheric neocortical cell numbers were obtained from pre-selected groups to test the potential effect of MAM on neuron number. No significant differences were observed in volume of the pre-selected regions of MAM intoxicated pigs nor in estimates of total neocortical neuron number.

Cerebral Cortical Abnormalities Seen in a Non-Human Primate Model of Prenatal Cocaine Exposure are not Related to Vasoconstriction

In our previous studies [J. Comp. Neurol. 435 (2001) 263] we demonstrated that rhesus monkeys born to mothers receiving cocaine orally during the period of pregnancy when neurons destined for the cerebral neocortex were generated displayed inappropriate positioning of neocortical neurons, loss of normal neocortical lamination, and reduction in neocortical volume, density and total number of neocortical neurons. In the present paper, we examined whether these cytoarchitectural abnormalities were related to the relatively high blood levels of the cocaine metabolite, benzoylecgonine, associated with oral cocaine administration. We also evaluated the role of vasoconstriction of the uteroumbilical and fetal brain vessels in the generation of these abnormalities. For these purposes, we compared cerebral neocortical cytoarchitecture in 2-month-old monkeys from five groups of mothers: (1) a drug-naı̈ve group, (2) a cocaine-treated group, (3) a group treated with benzoylecgonine at doses producing higher blood levels of this metabolite and stronger vasoconstriction that those in the cocaine-treated group, (4) a group treated with cocaine plus the vasodilator, isosorbide dinitrate, which counteracted the vasoconstrictive actions of cocaine, and (5) a group exposed to isosorbide dinitrate alone. All treatments were carried out from the 45th through 102nd day of pregnancy. We found that the general appearance of the neocortex and the position and number of neocortical neurons in the offspring of benzoylecgonine- and isosorbide dinitrate-treated mothers were indistinguishable from those in the offspring of drug-naı̈ve mothers. In contrast, significant alterations in these parameters (similar to those seen in our previous studies) were observed in the offspring of cocaine and cocaine + isosorbide dinitrate-treated mothers. These findings suggest that it is unlikely that either benzoylecgonine or vasoconstriction are responsible for the abnormalities seen in the neocortical cytoarchitecture in our non-human primate model of prenatal cocaine exposure.

Neocortical Glial Cell Numbers in Alzheimer’s Disease

Most studies agree that specific regions of the hippocampus and specific subcortical regions show neuronal loss in Alzheimer’s disease (AD). The aim of the study was to use design-based stereological methods to obtain an estimate of the total glial cell population in 14 AD cases and 20 controls to determine whether brains from AD patients have a different number of neocortical glial cells than controls. The mean total number of neocortical glial cells was 25.9 × 10⁹ for the AD group and 29.1 × 10⁹ for the control group, 2p = 0.18. The mean total number of neocortical neurons was 18.9 × 10⁹ for the AD group and 21.2 × 10⁹ for the control group, 2p = 0.059. Estimates of the sum of all glial cells and neurons in the neocortex were in the order of 50 billion cells with a glia to neuron ratio of 1.37 in both groups.

Primates exposed to cocaine in utero display reduced density and number of cerebral cortical neurons.

This study examined the effects of cocaine use during the second trimester of pregnancy on cerebral neocortical volume and density, and total number of neocortical neurons and glia in offspring. We also evaluated the extent of postnatal recovery of cytoarchitectural abnormalities previously observed in the neocortex of two-month-old primates born from cocaine-treated mothers (Lidow [1995] Synapse 21:332-334). Pregnant monkeys received cocaine orally (20 mg/kg/day) from the 40th to 102nd days of pregnancy (embryonic day [E]40-E102). On E64 and E65, the animals were injected with [(3)H]thymidine. Cerebral hemispheres of the offspring were examined at three years of age. We found a reduction in the neocortical volume and density and total number of neocortical neurons. The observed reduction in neuronal number within the neocortex was not accounted for by the increase in the number of neurons in the white matter of cocaine-exposed animals, because the number of these "extra" neurons was equal to only half that of missing neurons. We detected no significant changes in the number of neocortical glia. The cytoarchitectural abnormalities in the neocortex of prenatally cocaine-exposed three-year-old monkeys closely resembled previously described neocortical abnormalities in similarly exposed two-month-old animals: the neocortex lacked a discernible lamination; the majority of the cells labeled by [(3)H]thymidine injected during neocortical neurogenesis did not reach their proper position within the cortical plate. Therefore, postnatal maturation is not associated with significant improvement in neocortical organization in primates prenatally exposed to cocaine. There was, however, a postnatal recovery of low glial fibrillary acidic protein (GFAP) immunoreactivity previously observed in 2-month-old cocaine-exposed animals.

Preferential loss of large neocortical neurons during HIV infection: a study of the size distribution of neocortical neurons in the human brain

The infection with human immunodeficiency virus (HIV) is associated with a global and severe loss of neocortical neurons. However, there is limited knowledge concerning whether all neurons are equally susceptible to damage during HIV infection. Other studies have reported low vulnerability of small interneurons and high vulnerability of large motor neurons. Thus, it is natural to suggest that HIV infection, which causes damage to neurons in several ways, may predominantly affect large neurons in the neocortex. In this study we have used three unbiased stereological probes: Cavalieri's principle, the optical dissector and the rotator method, to obtain both total neocortical neuron number and their size distribution in formalin-fixed brains from six male acquired immunodeficiency syndrome (AIDS) patients and six male controls. The material is a selection of a large material choosing the youngest. The number of neurons in neocortex was reduced by 25% from 24.4×10 9 in controls to 18.3×10 9 in the AIDS patients; the reduction is similar to that of 27% found in the large material. In the normal size distribution of the neocortical neurons most neurons were smaller than 5000 μm 3 and no sampled neurons were larger than 28,000 μm 3. In addition, the absolute size distribution of neocortical neurons showed a significant decrease of the largest group of neurons by 50% (2 p=0.01) in the AIDS group, while there was no significant difference between controls and AIDS patients in the number of small neurons. The pattern of reduction in the number of large neocortical neurons was found in frontal, temporal, parietal as well as in occipital regions. This suggests that large neurons are more sensitive than small neurons to the destruction caused by the HIV infection.

Neocortical neuron number in humans: Effect of sex and age

Modern stereological methods provide precise and reliable estimates of the number of neurons in specific regions of the brain. We decided to estimate the total number of neocortical neurons in the normal human brain and to analyze it with respect to the major macro- and microscopical structural components, to study the internal relationships of these components, and to quantitate the influence of important physiological variables on brain structure. The 94 brains reported represent a consecutive collection of brains from the general Danish population. The average numbers of neocortical neurons were 19 billion in female brains and 23 billion in male brains, a 16% difference. In our study, which covered the age range from 20 years to 90 years, approximately 10% of all neocortical neurons are lost over the life span in both sexes. Sex and age were the main determinants of the total number of neurons in the human neocortex, whereas body size, per se, had no influence on neuron number. Some of the data presented have been analyzed by using new mathematical designs. An equation predicting the total neocortical neuron number in any individual in which sex and age are known is provided.

Forebrain hypoplasia following acute prenatal ethanol exposure: quantitative analysis of effects on specific forebrain nuclei

The effects of acute prenatal exposure to ethanol on the volumes and neuronal populations of selected forebrain nuclei of postnatal animals have been examined in a mouse model. Pregnant mice were exposed to ethanol (25% ethanol, either two doses at 0.015 ml/g separated by 4 hrs, or a single dose at 0.03 ml/g) on the 8th gestational day and the cytoarchitecture of the basal forebrain, paleo- and neocortex examined quantitatively at P15. Significant reductions in the volume and total number of neurons of ventromedial and central forebrain structures, such as the olfactory bulb, septal nuclei, diagonal band nuclei and caudatoputamen, were observed in mice exposed to the divided ethanol dose, but not following the single dose. The neocortex and primary olfactory cortex were also reduced in volume in offspring exposed to the divided ethanol dose. However increased neuronal density in some neocortical regions of ethanol-exposed offspring suggests that the total number of neocortical neurons is not significantly affected by acute ethanol exposure. The findings indicate that pulse exposure to ethanol on a single day of early development causes deficits in neuronal populations of the ventromedial forebrain and caudatoputamen even in offspring without other major malformations. The results also indicate that caution should be exercised in interpreting the significance of nuclear volume reduction in human infants with fetal alcohol syndrome (FAS) in the absence of neuronal density estimates.

Solutions to old problems in the quantitation of the central nervous system

New stereological techniques, superior to conventional methods in quantitating macroscopic and microscopic structures in the central nervous system, have been developed within the last decade. By the use of a new counting method, the dissector, it is possible to obtain an efficient and yet precise estimate of the total number of neurons in any specific region, where a delineation of the region can be made, and the cells identified. The method has been applied to brains from patients with different neurological disorders. The latest effort has concentrated on the estimation of the total neocortical neuron number in brains from normal individuals of both sexes in the age from 20 to 90 years to see whether there are differences in total neocortical neuron numbers between males and females.

Six billion neurons lost in AIDS. A stereological study of the neocortex.

Human immunodeficiency virus type 1 (HIV1) is neurotropic. One of the morphological changes that is seen in patients with acquired immunodeficiency syndrome (AIDS) is cerebral atrophy affecting various structures including the neocortex. The cause of atrophy is not known. The total number of neocortical neurons was estimated in formalin fixed brains of 12 males with AIDS and 12 male controls matched for age and height. The mean number of neocortical neurons was 16.0 x 10(9) (coefficient of variation = 0.11) in the AIDS patients compared with 21.9 x 10(9) (coefficient of variation = 0.22) in the controls, a difference of approximately six billion (p < 0.005, 2-tailed). The global neuronal loss was 37%, and affected all four neocortical lobes. Ten patients did not have a history of central nervous system symptoms; two patients had a history of dementia. The number of neurons in the AIDS cases was not associated with dementia. AIDS is the first disease in which a global loss of neocortical neurons has been demonstrated using unbiased stereological methods. The loss of more than one third of the neurons may partly explain the cortical atrophy. Focal neuron loss has been reported by several authors, but none have been based on unbiased methods. In this group of AIDS patients the severe loss of neurons did not correspond to neurological deficits.

The 6th Sandbjerg Symposium. Dementia Research in Denmark. The Danish Society of Neurosciences. May 1992. Abstracts.

Acta Neurologica ScandinavicaVolume 86, Issue 5 p. 532-540 The Sixth Sandbjerg Symposium, May 1992 Dementia Research in Denmark. The Danish Society of Neurosciences First published: November 1992 https://doi.org/10.1111/j.1600-0404.1992.tb05139.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract New strategies in dementia research, Nordberg A Dementia research in Denmark, Fog R Neurotoxic and neurotrophic factors in Alzheimer dementia, Jørgensen OS Alzheimer's disease and amyloid precursor protein, Linnemann D Neuron network in an experimental set-up. focus on intracellular calcium, Undén M Molecular approaches towards understanding ageing, Rattan SIS Jørgensen AL New stereology on the neurosciences: neurostereology, Pakkenberg B Neuron loss in the aging human hippocampus, West MJ, Gundersen HJG No neocortical nerve cell loss in brains from women patients with senile dementia of Alzheimer's type, Regeur L Total neocortical neuronnumber in brains from chronic alcoholics, Jensen GB Quantitation of the human cerebellum and volume estimation of Purkinje cells, Andersen BB, Korbo L Learning and memory models for dementia including the Alzheimer type, Christensen AV, Scheel-Krüger J Reversible dementia, indications for brain biopsy in dementia, Gjerris F, Juhler M, Garde L Secundary psychiatric phenomena in Alzheimer's disease. Borderland between psychiatry and neuropsychology, Gulmann N Autobiographical memory in normals and in demented patients (Alzheimer type), Fromholt F Incidence and prevalence of dementia in the Odense elderly, A project, Lolk A, Nielsen H, Kragh-Ssrensen P Excitatory amino acids and serotonin in dementia, Møller SE SPECT with [99mTc]-d,l-HMPAO in dementia of the Alzheimer type: topographical heterogeneity of neocortical cerebral blood flow deficits, Waldemar G, Bruhn P, Kristensen M, Johnsen A, Lassen NA, Paulson OB Correlation between ICP, diagnostic imagine and biopsy in the diagnose of dementia, Juhler M, Garde L, Waldemer G, Gjerris F Muscarinic agonists as possible drugs against senile dementia of Alzheimer's type, Meier E, Hyttel J Clinical research strategies and visions, Kragh-Sørensen P Volume86, Issue5November 1992Pages 532-540 RelatedInformation

Total number and mean cell volume of neocortical neurons in rats exposed to 2,5-hexanedione with and without acetone

The toxicological effects of 2,5-hexanedione (2,5-HD) alone and combined with acetone on the number and size of neurons in the cerebral cortex of rats were evaluated with stereological techniques. Thirty rats were equally divided into three groups: One control, one receiving 0.5% 2,5-HD, and one receiving 0.5% 2,5-HD and 0.5% acetone in the drinking water for seven weeks. Unbiased estimates of the total number of neocortical neurons, as well as the mean neuronal nuclei and cell body volumes were obtained from systematically sampled 3.5-μm sections. The total number of neurons in the 2,5-HD group was significantly smaller than the control group ( p<0.05, one-tailed t-test). Both test groups showed significant changes in the mean cell body volume: Compared with the control group, animals exposed to 2,5-HD had 11% smaller cell body volumes while animals exposed to 2,5-HD and acetone had 13% larger cell body volumes. These data represent the first unbiased estimation of mean cell volume in toxicology. We propose the nucleator method as an efficient and accurate tool for estimating quantitative changes in toxicological research.

The total number of neurons in the human neocortex unbiasedly estimated using optical disectors

An efficient method is presented for obtaining, in under 4 h, an unbiased estimate of the total number of neurons in the human neocortex, with a coefficient of error on the estimate of approximately 5%. The novel sampling scheme used in this study is unbiased and was designed so that only a small amount of neocortical grey matter had to be removed. Hence, the majority of the cerebral grey matter and all the internal grey matter was left intact for further resampling and analysis. Each cerebral hemisphere was subdivided into the four major neocortical regions, sliced coronally at 7-mm intervals and the volume of the neocortex determined using Cavalieri's principle. Uniform sampling of neocortex was performed in the hemisphere followed by regional subsampling with a varying sampling fraction being taken from each region. Neuronal density estimates were made in thick plastic sections using optical disectors. Shrinkage estimates were made in parallel with the number estimates and found to be negligible. The total number of neocortical neurons in the right hemisphere of five normal 80-year-old men was found to be 13.7 x 10(9) with an inter-individual coefficient of variation of 12%.