Cited by 1,153Point processes and geometric inequalitiesMemory and Neural MechanismsClassical Anatomy and Histology

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Unbiased stereological estimation of the number of neurons in the human hippocampus

West, Mark J., Gundersen, H. J. G.·1990·Journal of Comparative Neurology

Open this paper in CoChat — free account

Abstract

The total numbers of neurons in five subdivisions of human hippocampi were estimated using unbiased Stereological principles and systematic sampling techniques. The method addresses the problems associated with the results and conclusions of previous quantitative studies, virtually all of which have been based on biased estimates of neuron densities. For each subdivision, the total number of neurons was calculated as the product of the estimate of the volume of the neuron‐containing layers and the estimate of the numerical density of neurons in the layers. Each hippocampus was cut into 3‐mm‐thick slabs, transverse to the rostrocaudal axis. One 70‐μUm‐thick section from each slab was used in the analysis. The volumes of the layers containing neurons in five major subdivisions of the hippocampus (granule cell layer, hilus, CA3–2, CA1, and subiculum) were estimated with point‐counting techniques after delineation of the layers on each section. The numerical densities of neurons in each subdivision were estimated on the same sections with optical directors. The sampling used in both estimates was performed systematically in all three dimensions. In an example of five hippocampi, the mean numbers of neurons (CV = SD/mean) in the different subdivisions were as follows: granule cells 15 × 10 6 (0.28), hilus 2.0 × 10 6 (0.16), CA3‐2 2.7 × 10 6 (0.22), CA1 16 × 10 6 (0.32), subiculum 4.5 × 10 6 (0.19). The stereological measurements contributed approximately 25% of the observed variance. Among the five subjects there was a significant inverse relationship between age (which ranged from 47 to 85 years) and the total number of neurons in CA1 (which ranged from 24 to 11 × 10 6). An optimized sampling scheme for studies of the number of neurons in the human hippocampus has been designed on the basis of an analysis of variance of the estimates at different levels of the sampling scheme. Counting neurons in the five subdivisions of the human hippocampus with the optimized sampling scheme takes less than 4 hours.

Integrity signals

Registry

Crossref · 10.1002/cne.902960102

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Estimation of nuclear population from microtome sections
Abercrombie, M. (1946) · The Anatomical Record · doi:10.1002/ar.1090940210 · Cited by 4,363
The efficiency of systematic sampling in stereology and its prediction*
Gundersen, H. J. G., & Jensen, E. B. V. (1987) · Journal of Microscopy · doi:10.1111/j.1365-2818.1987.tb02837.x · Cited by 3,519
Self-citation
The unbiased estimation of number and sizes of arbitrary particles using the disector
Sterio, D. C. (1984) · Journal of Microscopy · doi:10.1111/j.1365-2818.1984.tb02501.x · Cited by 2,533
The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis
Gundersen, H. J. G., Bagger, P. V., Bendtsen, T. F., Evans, S. M., Korbo, L., Marcussen, N., Møller, A., Nielsen, K. N., Nyengaard, J. R., Pakkenberg, B., et al. (1988) · Apmis · doi:10.1111/j.1699-0463.1988.tb00954.x · Cited by 2,480
Self-citation
Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus
Zola-Morgan, S., Squire, L., & Amaral, D. (1986) · The Journal of Neuroscience · doi:10.1523/jneurosci.06-10-02950.1986 · Cited by 1,997
Studies on the structure of the cerebral cortex. II. Continuation of the study of the ammonic system.
de Nó, R. L. (1934) · Cited by 1,974
Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson.
Gundersen, H. J. G. (1986) · PubMed · Cited by 1,658
Self-citation
Stereology of arbitrary particles*
Gundersen, H. J. G. (1986) · Journal of Microscopy · doi:10.1111/j.1365-2818.1986.tb02764.x · Cited by 1,444
Self-citation
Notes on the estimation of the numerical density of arbitrary profiles: the edge effect
Gundersen, H. J. G. (1977) · Journal of Microscopy · doi:10.1111/j.1365-2818.1977.tb00062.x · Cited by 1,265
Self-citation
Neuron numbers and dendritic extent in normal aging and Alzheimer’s disease
Coleman, P. D., & Flood, D. G. (1987) · Neurobiology of Aging · doi:10.1016/0197-4580(87)90127-8 · Cited by 772

Flagged first, then by citations

Show all 47 references

Research works printed but not linked: 3

Floderus S., 1944, Untersuchungen über den Bau der menschlichen Hypophyse mit besonderer Berücksichtigung der quantitativen mikromorphologischen Verhältnisse, Acta Pathol. Microbiol. Immunol. Scand., 53, 1
Krekule I., 1989, Computer graphics enhancement of measures in stereology, Acta. Stereologica., 8, 533
Stephan H., 1975, Handbuch der Mikros‐kopischen Anatomic des Menschen, Bd 4: Nervensystem, Teil 9, 1

Sorted by citations

Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994
“Vref scheme has the disadvantage that the shrinkage or expansion that occurs between the preparation of the blocks and the analysis of the sections must be known and that the sectional area of the extensive thin layers, like the dentate granule cell layer must be estimated with a somewhat involved point counting schem…”
BackgroundMethodInfluentialSelf-citation
Time Is Brain—Quantified
Saver, J. L. (2005) · Stroke · doi:10.1161/01.str.0000196957.55928.ab · Cited by 2,197
Dynamics of hippocampal neurogenesis in adult humans
Spalding, K. L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H. B., Boström, E., Westerlund, I., Vial, C., Buchholz, B. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.002 · Cited by 1,841
Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796
“Detailed descriptions of these techniques have been presented elsewhere (West and Gundersen, 1990).”
MethodInfluential
Reconstruction and Simulation of Neocortical Microcircuitry
Markram, H., Muller, E., Ramaswamy, S., Reimann, M. W., Abdellah, M., Sanchez, C. A., Ailamaki, A., Alonso-Nanclares, L., Antille, N., Arsever, S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.029 · Cited by 1,557
“Layer boundaries and densities per layer were computed on slices using optical dissectors on NeuN-stained tissue (West and Gundersen, 1990; Williams and Rakic, 1988) and Stereo Investigator software (StereoInvestigator 7.”
Method
Life and Death of Neurons in the Aging Brain
Morrison, J. H., & Hof, P. R. (1997) · Science · doi:10.1126/science.278.5337.412 · Cited by 1,344
Human Hippocampal Neurogenesis Persists throughout Aging
Boldrini, M., Fulmore, C. A., Tartt, A. N., Simeon, L. R., Pavlova, I., Poposka, V., Rosoklija, G. B., Stankov, A., Arango, V., Dwork, A. J., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.03.015 · Cited by 1,345
“…of the hippocampus, treated tissue at 80°C for 1 hr and at low pH to obtain deparaffinization and antigen retrieval, and assessed cell density without using stereology, which is the gold standard, given that cell density does not necessarily reflect total cell number (West and Gundersen, 1990).”
Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease
West, M. J., Coleman, P. D., Flood, D. G., & Troncoso, J. C. (1994) · The Lancet · doi:10.1016/s0140-6736(94)92338-8 · Cited by 1,267
Self-citation
Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease
Giannakopoulos, P., Herrmann, F. R., Bussière, T., Bouras, C., Kövari, E., Perl, D. P., Morrison, J. H., Gold, G., & Hof, P. R. (2003) · Neurology · doi:10.1212/01.wnl.0000063311.58879.01 · Cited by 1,118
Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models
Hsia, A. Y., Masliah, E., McConlogue, L., Yu, G.-Q., Tatsuno, G., Hu, K., Kholodenko, D., Malenka, R. C., Nicoll, R. A., & Mucke, L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3228 · Cited by 1,123
Computational analysis of the role of the hippocampus in memory
Treves, A., & Rolls, E. T. (1994) · Hippocampus · doi:10.1002/hipo.450040319 · Cited by 1,272
The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting
von Bartheld, C. S., Bahney, J., & Herculano‐Houzel, S. (2016) · Journal of Comparative Neurology · doi:10.1002/cne.24040 · Cited by 1,063
“Thus, utilization of the Giemsa stain predates the adoption of this stain by Gundersen, West, and Pakkenberg for their resin sections in the 1980s and 1990s (e.g., Gundersen et al., 1988; West and Gundersen, 1990; Regeur et al., 1994a).”
Method
Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment
Scheff, S. W., Price, D. A., Schmitt, F. A., & Mufson, E. J. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.012 · Cited by 1,017
New stereological methods for counting neurons
West, M. J. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90112-o · Cited by 940
Self-citation
An Official Research Policy Statement of the American Thoracic Society/European Respiratory Society: Standards for Quantitative Assessment of Lung Structure
Hsia, C. C. W., Hyde, D. M., Ochs, M., & Weibel, E. R. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200809-1522st · Cited by 906
Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala
Ghashghaei, H. T., Hilgetag, C. C., & Barbas, H. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.09.046 · Cited by 845
“We then employed standard stereological procedures to estimate the areal and laminar density of boutons, using the optical fractionator according to the method described by West and Gundersen (e.g., Gundersen et al., 1988; West and Gundersen, 1990).”
Method
Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model
Choi, S. H., Bylykbashi, E., Chatila, Z. K., Lee, S. W., Pulli, B., Clemenson, G. D., Kim, E., Rompala, A., Oram, M. K., Asselin, C., et al. (2018) · Science · doi:10.1126/science.aan8821 · Cited by 802
“The total number of GCL neurons was obtained by using the formula developed as described previously (55).”
Method
Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network
Treves, A., & Rolls, E. T. (1992) · Hippocampus · doi:10.1002/hipo.450020209 · Cited by 725
“Interestingly, it was recently reported (West and Gundersen, 1990) that, when correcting appropriately for postmortem shrinkage of tissues, the numbers for humans increase to 15 x 106 :t 28% (DG), 2.7 x 106 :t 22% (CA3), and 16 x 166 :t 32% (CAl). tex, make synapses on the apical dendrites of CA3…”
BackgroundInfluential
Antidepressants increase neural progenitor cells in the human hippocampus
Boldrini, M., Underwood, M. D., Hen, R., Rosoklija, G. B., Dwork, A. J., John Mann, J., & Arango, V. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.75 · Cited by 686
Design-based stereology in neuroscience.
Schmitz, C., & Hof, P. R. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.08.050 · Cited by 681
“Estimated total numbers of neurons within a BROI can be obtained by the " V Ref ϫN V " method (West and Gundersen , 1990), i.e. by calculating the product of the mean neuron density within the unbiased virtual counting spaces (N V ) and the global volume of the BROI (V Ref ; estimated with…”
Method
A model for memory systems based on processing modes rather than consciousness
Henke, K. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2850 · Cited by 739
Microstructure of the neocortex: comparative aspects
DeFelipe, J., Alonso-Nanclares, L., & Arellano, J. I. (2002) · Journal of Neurocytology · doi:10.1023/a:1024130211265 · Cited by 686
Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice
Shi, Q., Chowdhury, S., Ma, R., Le, K. X., Hong, S., Caldarone, B. J., Stevens, B., & Lemere, C. A. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6295 · Cited by 593
“M. J. West, H. J. G. Gundersen, Unbiased stereological estimation of the number of neurons in the human hippocampus.”
Method
Regionally specific loss of neurons in the aging human hippocampus
West, M. J. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90113-p · Cited by 626
Self-citation
Neocortical glial cell numbers in human brains
Pelvig, D. P., Pakkenberg, H., Stark, A. K., & Pakkenberg, B. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.04.013 · Cited by 601
A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause
Hansen, K. R., Knowlton, N. S., Thyer, A., Charleston, J. S., Soules, M. R., & Klein, N. A. (2008) · Human Reproduction · doi:10.1093/humrep/dem408 · Cited by 564
Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps
Apostolova, L. G., Dutton, R. A., Dinov, I. D., Hayashi, K. M., Toga, A. W., Cummings, J. L., & Thompson, P. M. (2006) · Archives of Neurology · doi:10.1001/archneur.63.5.693 · Cited by 553
Attenuation of Delayed Neuronal Death after Mild Focal Ischemia in Mice by Inhibition of the Caspase Family
Endres, M., Namura, S., Shimizu‐Sasamata, M., Waeber, C., Zhang, L., Gómez‐Isla, T., Hyman, B. T., & Moskowitz, M. A. (1998) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199803000-00002 · Cited by 543
“The appropriateness of the sampling scheme chosen was evaluated by calculating the precision of the esti mates in each animal, expressed as the coefficient of error (West and Gundersen, 1990).”
Method
Dynamics of Oligodendrocyte Generation and Myelination in the Human Brain
Yeung, M. S. Y., Zdunek, S., Bergmann, O., Bernard, S., Salehpour, M., Alkass, K., Perl, S., Tisdale, J., Possnert, G., Brundin, L., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.011 · Cited by 541
A consideration of neural counting methods
Coggeshall, R. E. (1992) · Trends in Neurosciences · doi:10.1016/0166-2236(92)90339-a · Cited by 540
The cerebral cortex is damaged in chronic alcoholics
Kril, J. J., Halliday, G. M., Svoboda, M. D., & Cartwright, H. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00083-3 · Cited by 507
Aβ Deposition Is Associated with Neuropil Changes, but not with Overt Neuronal Loss in the Human Amyloid Precursor Protein V717F (PDAPP) Transgenic Mouse
Irizarry, M. C., Soriano, F., McNamara, M., Page, K. J., Schenk, D., Games, D., & Hyman, B. T. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-18-07053.1997 · Cited by 497
“Neuron counts were performed using the optical disector technique (West and Gundersen, 1990) in 40 mM cresyl violet-stained coronal sections spaced 240 mM apart.”
Method
Aging and the human neocortex
Pakkenberg, B. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00151-1 · Cited by 485
“…aging and disease showed normal individuals to lose neurons in two regions of the hippocampus, subiculum and the hilus as a function of age, while patients with AD lost more neurons in these two regions than normal aging individuals (West and Gundersen, 1990; West et al., 1994; Simic et al., 1997).”
Background
Three distinct families of GABAergic neurons in rat visual cortex
Gonchar, Y. (1997) · Cerebral Cortex · doi:10.1093/cercor/7.4.347 · Cited by 481
The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease
Bobinski, M., de Leon, M. J., Wegiel, J., DeSanti, S., Convit, A., Saint Louis, L. A., Rusinek, H., & Wisniewski✠, H. M. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00476-5 · Cited by 455
Complement in the brain
Veerhuis, R., Nielsen, H. M., & Tenner, A. J. (2011) · Molecular Immunology · doi:10.1016/j.molimm.2011.04.003 · Cited by 436
What causes the hippocampal volume decrease in depression?: Are neurogenesis, glial changes and apoptosis implicated?
Czéh, B., & Lucassen, P. J. (2007) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-007-0728-0 · Cited by 419
“7 million pyramidal neurons in the CA2-3 region, plus ~2 million neurons located in the hilus [112].”
Background
Region-specific Dissociation of Neuronal Loss and Neurofibrillary Pathology in a Mouse Model of Tauopathy
Spires, T. L., Orne, J. D., SantaCruz, K., Pitstick, R., Carlson, G. A., Ashe, K. H., & Hyman, B. T. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050840 · Cited by 401
Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology
Perez-Nievas, B. G., Stein, T. D., Tai, H.-C., Dols-Icardo, O., Scotton, T. C., Barroeta-Espar, I., Fernandez-Carballo, L., de Munain, E. L., Perez, J., Marquie, M., et al. (2013) · Brain · doi:10.1093/brain/awt171 · Cited by 387
“Stereologically-based counts of neurofibrillary tangles, neurons, GFAP-positive astrocytes and CD68-positive microglial cells were performed as previously described (West and Gundersen, 1990; Gomez-Isla et al., 1996).”
Method
Age-associated increases of α-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson's disease?
Chu, Y., & Kordower, J. H. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.08.021 · Cited by 423
“The coefficients of error (CE) were calculated according to the procedure of Gunderson and colleagues as estimates of precision (West and Gundersen, 1990; Schmitz and Hof, 2000).”
Method
Dopamine depletion increases the power and coherence of β‐oscillations in the cerebral cortex and subthalamic nucleus of the awake rat
Sharott, A., Magill, P. J., Harnack, D., Kupsch, A. R., Meissner, W. G., & Brown, P. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03973.x · Cited by 391
“Unbiased stereological techniques (Gundersen et al., 1988; West & Gundersen, 1990; West, 1999) were used to estimate cell number in the substantia nigra pars compacta (SNc).”
Method
The multifarious hippocampal mossy fiber pathway: a review
Henze, D. A., Urban, N. N., & Barrionuevo, G. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00146-9 · Cited by 403
Use-Dependent Exaggeration of Neuronal Injury after Unilateral Sensorimotor Cortex Lesions
Kozlowski, D. A., James, D. C., & Schallert, T. J. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-15-04776.1996 · Cited by 389
“The coefficient of error (SD/mean) (Gundersen and Jensen, 1987; West and Gundersen, 1990) was Ͻ0.”
Background
Consequences of neonatal seizures in the rat: Morphological and behavioral effects
Gl, H., Gairsa, J., Chevassus-au-Louis, N., & Ben‐Ari, Y. (1998) · Annals of Neurology · doi:10.1002/ana.410440602 · Cited by 388
Hippocampal granule neuron number and dentate gyrus volume in antidepressant-treated and untreated major depression
Boldrini, M., Santiago, A. N., Hen, R., Dwork, A. J., Rosoklija, G. B., Tamir, H., Arango, V., & John Mann, J. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.5 · Cited by 361
A novel GSK-3β inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo
Serenó, L., Coma, M., Rodríguez, M., Sánchez-Ferrer, P., Sánchez, M. B., Gich, I., Agulló, J. M., Pérez, M., Avila, J., Guardia-Laguarta, C., et al. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.05.025 · Cited by 368
Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline
Shi, Q., Colodner, K. J., Matousek, S. B., Merry, K., Hong, S., Kenison, J. E., Frost, J. L., Le, K. X., Li, S., Dodart, J.-C., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1698-15.2015 · Cited by 368
“The number of neurons per section in each brain region was estimated using 15 optical dissectors and the Bioquant image analysis system according to the principles of Cavalieri (West and Gundersen, 1990).”
Method
Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB
Polito, V. A., Li, H., Martini‐Stoica, H., Wang, B., Li, Y., Xu, Y., Swartzlander, D. B., Palmieri, M., di Ronza, A., Lee, V. M. ‐., et al. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201303671 · Cited by 356
Autophagy flux in CA1 neurons of Alzheimer hippocampus: Increased induction overburdens failing lysosomes to propel neuritic dystrophy
Bordi, M., Berg, M. J., Mohan, P. S., Peterhoff, C. M., Alldred, M. J., Che, S., Ginsberg, S. D., & Nixon, R. A. (2016) · Autophagy · doi:10.1080/15548627.2016.1239003 · Cited by 353
Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage
Jones, T. A., & Schallert, T. J. (1992) · Brain Research · doi:10.1016/0006-8993(92)90356-e · Cited by 346
Delayed effects of chronic variable stress during peripubertal‐juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats
Isgor, C., Kabbaj, M., Akil, H., & Watson, S. J. (2004) · Hippocampus · doi:10.1002/hipo.10207 · Cited by 341
“The coefficient of variation was determined as described by West and Gundersen (1990) and was reported with the neuronal count estimates below.”
Method
Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress
Dong, H., Goico, B., Martin, M., Csernansky, C. A., Bertchume, A., & Csernansky, J. G. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.05.040 · Cited by 342
Mitochondrial function and morphology are impaired in parkin‐mutant fibroblasts
Mortiboys, H., Craig, K. J. T., Koopman, W. J. H., Klaffke, S., Abou‐Sleiman, P. M., Olpin, S. E., Wood, N. W., Willems, P. H. G. M., Smeitink, J. A. M., Cookson, M., et al. (2008) · Annals of Neurology · doi:10.1002/ana.21492 · Cited by 346
Complement C3 Deficiency Leads to Accelerated Amyloid Plaque Deposition and Neurodegeneration and Modulation of the Microglia/Macrophage Phenotype in Amyloid Precursor Protein Transgenic Mice
Maier, M., Peng, Y., Jiang, L., Seabrook, T. J., Carroll, M. C., & Lemere, C. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0829-08.2008 · Cited by 323
“The average number of neurons per section in the CA3 region of hippocampus was estimated using 12 optical dissectors and the Bioquant Image Analysis System according to the principle of Cavalieri (West and Gundersen, 1990).”
Method
Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim, J. G., Suyama, S., Koch, M., Jin, S., Argente-Arizon, P., Argente, J., Liu, Z.-W., Zimmer, M. R., Jeong, J. K., Szigeti-Buck, K., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3725 · Cited by 336
Neural Cell Adhesion Molecule-Stimulated Neurite Outgrowth Depends on Activation of Protein Kinase C and the Ras–Mitogen-Activated Protein Kinase Pathway
Kolkova, K., Novitskaya, V., Pedersen, N. M., Berezin, V., & Bock, E. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-06-02238.2000 · Cited by 335
A review of recent advances in stereology for quantifying neural structure
Mayhew, T. M. (1992) · Journal of Neurocytology · doi:10.1007/bf01191700 · Cited by 330
Age-induced white matter changes in the human brain: a stereological investigation.
Tang, Y., Nyengaard, J., Pakkenberg, B., & Gundersen, H. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00155-3 · Cited by 345
Self-citation
Hippocampal neurons in pre-clinical Alzheimer's disease.
West, M. J., Kawas, C. H., Stewart, W. F., Rudow, G. L., & Troncoso, J. C. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.12.005 · Cited by 317
“method combines fractionator sampling [12] with optical disector counting[13,37].”
MethodSelf-citation
The pre-mild cognitive impairment, subjective cognitive impairment stage of Alzheimer’s disease.
Reisberg, B., Prichep, L., Mosconi, L., John, E. R., Glodzik‐Sobanska, L., Boksay, I., Monteiro, I., Torossian, C., Vedvyas, A., Ashraf, N., et al. (2008) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2007.11.017 · Cited by 312
Hippocampal markers of age-related memory dysfunction: Behavioral, electrophysiological and morphological perspectives
Geinisman, Y., deToledo‐Morrell, L., Morrell, F., & Heller, R. E. (1995) · Progress in Neurobiology · doi:10.1016/0301-0082(94)00047-l · Cited by 327
Subregional hippocampal atrophy predicts Alzheimer's dementia in the cognitively normal
Apostolova, L. G., Mosconi, L., Thompson, P. M., Green, A. E., Hwang, K., Ramírez, A., Mistur, R. L., Tsui, W. H., & de Leon, M. J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.008 · Cited by 327
“Thus our conclusions in respect to selective subeld involvement are based on assumptions about the location f each subfield boundary made in consultation with two ell-established hippocampal histologic atlases (Duvernoy, 988; West and Gundersen, 1990).”
BackgroundMethod
Loss of Neurons in Magnocellular and Parvocellular Layers of the Lateral Geniculate Nucleus in Glaucoma
Yücel, Y. H. (2000) · Archives of Ophthalmology · doi:10.1001/archopht.118.3.378 · Cited by 305
“Stereological procedures that provide unbiased estimates of cell numbers were used.(19-22) Neurozoom software (Human Brain Project, La Jolla Calif) enabled digital superposition of the sampling grids on the tissue.”
Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation
Le, D. A., Wu, Y., Huang, Z., Matsushita, K., Plesnila, N., Augustinack, J. C., Hyman, B. T., Yuan, J., Kuida, K., Flavell, R. A., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.232473399 · Cited by 303
Hippocampal interneurons are abnormal in schizophrenia
Konradi, C., Yang, C. K., Zimmerman, E. I., Lohmann, K. M., Gresch, P., Pantazopoulos, H., Berretta, S., & Heckers, S. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.06.007 · Cited by 288
“Each human hippocampus contains approximately 10 million neurons, of which 90% are large, pyramidal-shaped, glutamatergic neurons and the remaining 10% are small, non-pyramidal, gammaamino-butyric acid (GABA)ergic neurons (Olbrich and Braak, 1985; West and Gundersen, 1990; Freund and Buzsaki, 1996).”
Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons
van den Munckhof, P., Luk, K. C., Ste‐Marie, L., Montgomery, J. A., Blanchet, P. J., Sadikot, A. F., & Drouin, J. (2003) · Development · doi:10.1242/dev.00464 · Cited by 303
“Unbiased estimates of midbrain DA neurons were obtained using the optical dissector method of West and Gundersen (West and Gundersen, 1990; West, 1993).”
Brain-derived neurotrophic factor/neurotrophin-4 receptor TrkB is localized on ganglion cells and dopaminergic amacrine cells in the vertebrate retina
Cellerino, A., & Köhler, K. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970915)386:1 · Cited by 149
High Mobility Group Box 1/Toll-like Receptor Danger Signaling Increases Brain Neuroimmune Activation in Alcohol Dependence
Crews, F. T., Qin, L., Sheedy, D. L., Vetreno, R. P., & Zou, J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.030 · Cited by 305
Activation of c-Jun N-Terminal Kinase and p38 in an Alzheimer's Disease Model Is Associated with Amyloid Deposition
Savage, M. J., Lin, Y.-G., Ciallella, J. R., Flood, D. G., & Scott, R. W. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03376.2002 · Cited by 291
“Neurons were counted with the CASTGrid System (Olympus Optical, Denmark, Copenhagen) using the optical dissector technique (West and Gundersen, 1990).”
Method
If you assume, you can make an ass out of u and me': a decade of the disector for stereological counting of particles in 3D space.
Mayhew, T. M., & Gundersen, H. J. G. (1996) · PubMed · Cited by 291
Self-citation
Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the developing rat hippocampus
Livy, D. J., Miller, E. K., Maier, S. E., & West, J. R. (2003) · Neurotoxicology and Teratology · doi:10.1016/s0892-0362(03)00030-8 · Cited by 290
NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration
Qin, L., & Crews, F. T. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-5 · Cited by 290
“optical disector method [34,35], which was calculated as follows:”
Method
Pyramidal cell regulation of interneuron survival sculpts cortical networks
Wong, F. K., Bercsenyi, K., Sreenivasan, V., Portalés, A., Fernández-Otero, M., & Marín, O. (2018) · Nature · doi:10.1038/s41586-018-0139-6 · Cited by 286
Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA A dysregulation and impaired spatial learning
Samuelsson, A., Jennische, E., Hansson, H., & Holmäng, A. B. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00268.2005 · Cited by 300
“Neuronal density in the hilus, CA1, CA2, and CA3 regions was estimated as the average percentage of Nissl-stained neurons in five counting frames (50 50 m) distributed systematically and randomly in the study area, as described previously (62).”
Method
Age-related differences in the functional connectivity of the hippocampus during memory encoding
Grady, C. L., McIntosh, A. R., & Craik, F. I. M. (2003) · Hippocampus · doi:10.1002/hipo.10114 · Cited by 277
“For example, one study reported a loss of neurons in CA1 and subiculum with age, but not in other subdivisions of the hippocampus (Simic et al., 1997).”
Background
Neutralization of Transthyretin Reverses the Neuroprotective Effects of Secreted Amyloid Precursor Protein (APP) in APPSwMice Resulting in Tau Phosphorylation and Loss of Hippocampal Neurons: Support for the Amyloid Hypothesis
Stein, T. D., Anders, N. J., DeCarli, C. S., Chan, S. L., Mattson, M. P., & Johnson, J. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2211-04.2004 · Cited by 286
“Every sixth section was stained with cresyl violet , and neurons with healthy and intact nuclei were counted within the cornu ammonis 1 ( CA1 ) pyramidal neuronal field using the optical fractionator technique ( West and Gundersen , 1990 ) .”
Method
A quantitative study of the human cerebellum with unbiased stereological techniques
Andersen, B. B., Korbo, L., & Pakkenberg, B. (1992) · Journal of Comparative Neurology · doi:10.1002/cne.903260405 · Cited by 276
Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach
Schmitz, C., & Hof, P. R. (2000) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(00)00066-1 · Cited by 272
“(5) (West and Gundersen, 1990): nV×N=6ref×nV (5) To obtain estimates of the average total boundary length of the sections (B( ), a third set of rectangular lattices with uniform side length slB was placed in a systematic–random manner on the upper surface of the sections (Fig.”
BackgroundMethodInfluential
Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with down syndrome and in Ts65Dn mice
Contestabile, A., Fila, T., Ceccarelli, C., Bonasoni, P., Bonapace, L., Santini, D., Bartesaghi, R., & Ciani, E. (2007) · Hippocampus · doi:10.1002/hipo.20308 · Cited by 281
“In P30 animals, granule cell density (NV) in the granule cell layer of the DG was stereologically (West and Gundersen, 1990) determined in NeuN-stained section, by counting in one out of every 12 sections the number of granule cells present in dissectors with dimensions of 25 lm 3 25 lm 3 10 lm,…”
RESEARCH ARTICLE: Neurogenesis Impairment and Increased Cell Death Reduce Total Neuron Number in the Hippocampal Region of Fetuses with Down Syndrome
Guidi, S., Bonasoni, P., Ceccarelli, C., Santini, D., Gualtieri, F., Ciani, E., & Bartesaghi, R. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00113.x · Cited by 276
“Based on the Cavalieri principle (17, 52), we estimated the reference volume (Vref) of the granule cell layer, pyramidal layer, lamina principalis interna and lamina principalis externa of the PRES and EC and single cellular lamina of the LPHG by multiplying the sum of the areas measured in the series of sections by t…”
Method
A test of the adaptive specialization hypothesis: Population differences in caching, memory, and the hippocampus in black-capped chickadees (Poecile atricapilla).
Витальевич, П. В., & Clayton, N. S. (2002) · Behavioral Neuroscience · doi:10.1037/0735-7044.116.4.515 · Cited by 256
“In accordance with the Cavalieri principle (Gundersen & Jensen, 1987; West & Gundersen, 1990 ), we chose the first section randomly from the first 4 sections containing the hippocampus.”
MethodInfluential
Distribution and steroid hormone regulation of aromatase mRNA expression in the forebrain of adult male and female rats: A cellular-level analysis using in situ hybridization
Wagner, C. K., & Morrell, J. I. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960617)370:1 · Cited by 127
Self-citation
Adult neurogenesis in Humans
Bergmann, O., Spalding, K. L., & Frisén, J. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018994 · Cited by 256
Mapping local hippocampal changes in Alzheimer's disease and normal ageing with MRI at 3 Tesla
Frisoni, G. B., Ganzola, R., Canu, E., Rub, U., Pizzini, F. B., Alessandrini, F., Zoccatelli, G., Beltramello, A., Caltagirone, C., & Thompson, P. M. (2008) · Brain · doi:10.1093/brain/awn280 · Cited by 256
“For example, pyramidal cells are lost in the subiculum between age 30 and 60 years (Trillo and Gonzalo, 1992), but stabilize thereafter (West and Gundersen, 1990; Trillo and Gonzalo, 1992), while cell loss in the presubiculum and CA1 subfield is more linearly associated with increasing age at least…”
Background
Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain
Anton, E. S., Ghashghaei, H. T., Weber, J. L., McCann, C. M., Fischer, T. M., Cheung, I. D., Gassmann, M., Messing, A., Klein, R., Schwab, M. H., et al. (2004) · Nature Neuroscience · doi:10.1038/nn1345 · Cited by 256
“The numbers of calbindin + , calretinin + and GAD65 + cells in the periglomerular layer of the OB were estimated using the optical fractionator metho”
3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer's disease
Apostolova, L. G., Dinov, I. D., Dutton, R. A., Hayashi, K. M., Toga, A. W., Cummings, J. L., & Thompson, P. M. (2006) · Brain · doi:10.1093/brain/awl274 · Cited by 251
“A schematic of subregional hippocampal anatomy in 3D was prepared in consultation with two wellestablished sources (Duvernoy, 1988; West and Gundersen, 1990) (Fig.”
Method
Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury
Carlton, S. M., Du, J., Tan, H. Y., Nešić, O., Hargett, G. L., Bopp, A. C., Yamani, A., Lin, Q., Willis, W. D., & Hulsebosch, C. E. (2009) · Pain · doi:10.1016/j.pain.2009.09.030 · Cited by 251
“Using ‘‘fractionator sampling” [28,93], total numbers of cresyl violet stained neurons and numbers of ATF3-labeled neurons were estimated by multiplying ‘‘Q-” by the reciprocal of the fraction (1/f) of each sampled section pair.”
Method
Synaptic organization of projections from the amygdala to visual cortical areas TE and V1 in the macaque monkey
Freese, J. L., & Amaral, D. G. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.20945 · Cited by 246
“The volumes of these boutons were measured according to the Cavalieri principal (Gundersen and Jensen, 1987; West and Gundersen, 1990).”
Method
Hippocampal Formation
Insausti, R., & Amaral, D. G. (2004) · Elsevier eBooks · doi:10.1016/b978-012547626-3/50024-7 · Cited by 256
Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy
Smith, D. E., Roberts, J. A., Gage, F. H., & Tuszynski, M. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.19.10893 · Cited by 244
Feature article: are neurons lost from the primate cerebral cortex during normal aging?
Peters, A. (1998) · Cerebral Cortex · doi:10.1093/cercor/8.4.295 · Cited by 245
“Initially the study concentrated on the CA1 and subicular subfields because of the prominent cell loss reported there in humans (West and Gundersen, 1990) and monkeys (Brizzee et al., 1980).”
Background
Quantitative Architecture Distinguishes Prefrontal Cortical Systems in the Rhesus Monkey
Dombrowski, S. M. (2001) · Cerebral Cortex · doi:10.1093/cercor/11.10.975 · Cited by 240
“The density of neurons and glia was estimated using a counting method adapted from previous studies (Sterio, 1984; Braendgaard and Gundersen, 1986; Williams and Rakic, 1988; Gundersen et al., 1988; West and Gundersen, 1990; West, 1993) [for a review see (Coggeshall and Lekan, 1996)].”
Method
Correlates of hippocampal neuron number in Alzheimer's disease and ischemic vascular dementia
Zarow, C., Vinters, H. V., Ellis, W. G., Weiner, M. W., Mungas, D., White, L., & Chui, H. C. (2005) · Annals of Neurology · doi:10.1002/ana.20503 · Cited by 241
“One gallocyanine-stained section was systematically chosen from each slab, and the CA1 and CA2 regions were identified and outlined on the coverslip using waterproof markers.(17) The slide was placed on the microscope stage in a random orientation and overlaid with a uniform grid.”
Method
From genotype to phenotype: A clinical, pathological, and biochemical investigation of frontotemporal dementia and parkinsonism (FTDP-17) caused by the P301L tau mutation
Nasreddine, Z. S., Loginov, M., Clark, L. N., Lamarche, J. B., Miller, B. L., Lamontagne, A., Zhukareva, V. A., Lee, V. M. ‐., Wilhelmsen, K. C., & Geschwind, D. H. (1999) · Annals of Neurology · doi:10.1002/1531-8249(199906)45:6 · Cited by 135
Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus
Redila, V. A., & Christie, B. R. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.10.050 · Cited by 244
“This represents some 6% of a structure that is stimated to be composed of some 2.4 million neurons Cameron and McKay, 2001; West and Gundersen, 1990). oreover, the number of new neurons being produced is ikely much larger in animals that exercise (Eadie et al., 005).”
BackgroundInfluential
Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction
Annese, J., Schenker-Ahmed, N. M., Bartsch, H., Maechler, P., Sheh, C., Thomas, N., Kayano, J., Ghatan, A., Bresler, N., Frosch, M. P., et al. (2014) · Nature Communications · doi:10.1038/ncomms4122 · Cited by 234
“Additional quantitative analyses involving unbiased stereological methods can provide information regarding neuronal size and number 43 in this region.”
Method
Age-Related Amyloid β Deposition in Transgenic Mice Overexpressing Both Alzheimer Mutant Presenilin 1 and Amyloid β Precursor Protein Swedish Mutant Is Not Associated with Global Neuronal Loss
Takeuchi, A., Irizarry, M. C., Duff, K., Saido, T. C., Hsiao Ashe, K., Hasegawa, M., Mann, D. M. A., Hyman, B. T., & Iwatsubo, T. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64544-0 · Cited by 229
Oxygen causes cell death in the developing brain
Felderhoff‐Mueser, U., Bittigau, P., Sifringer, M., Jarosz, B., Korobowicz, E. M., Mahler, L., Piening, T., Moysich, A., Grune, T., Thor, F., et al. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.07.019 · Cited by 229
Layer I of primary sensory neocortex: where top-down converges upon bottom-up
Cauller, L. (1995) · Behavioural Brain Research · doi:10.1016/0166-4328(95)00032-1 · Cited by 228
Spiny calretinin-immunoreactive neurons in the hilus and CA3 region of the rat hippocampus: Local axon circuits, synaptic connections, and glutamic acid decarboxylase 65/67 mRNA expression
Mart�nez, A., Ruiz, M., & Soriano, E. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990222)404:4 · Cited by 15

Authors: West, M. J., & Gundersen, H. J. G.
Affiliations: Aarhus University (DK)
Corresponding author: West, Mark J.
ORCID: West, Mark J.
Venue: Journal of Comparative Neurology
Publisher: Wiley
Published: 1990-06
Volume: 296
Issue: 1
Pages: 1-22
ISSN: 0021-9967 (ISSN-L)
1096-9861
DOI: 10.1002/cne.902960102
OpenAlex: W2014892312
Cited by: 1,153
References: 47
Citations by year: 2026: 7 · 2025: 13 · 2024: 10 · 2023: 17 · 2022: 24 · 2021: 22 · 2020: 24 · 2019: 19 · 2018: 40 · 2017: 27 · 2016: 32 · 2015: 30 · 2014: 38 · 2013: 40 · 2012: 41
FWCI: 46.01
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5244 d)
Locations: The Journal of Comparative Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: Sundhed og Sygdom, Det Frie Forskningsråd
Topics: Physical Sciences › Mathematics › Applied Mathematics › Point processes and geometric inequalities
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Health Sciences › Medicine › Anatomy › Classical Anatomy and Histology
Keywords: human hippocampus, neuron number estimation, neuronal density, unbiased stereology, optical disector, point counts, CA1, CA3, subiculum, granular layer, hilus, age-related neuronal loss
MeSH terms: Aged, Aged, 80 and over, Cell Count, Hippocampus, Humans, Middle Aged

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Unbiased stereological estimation of the number of neurons in the human hippocampus

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks