Journal of Autism and Developmental Disorders

, Volume 46, Issue 4, pp 1307–1318 | Cite as

Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

  • E. C. AzmitiaEmail author
  • Z. T. Saccomano
  • M. F. Alzoobaee
  • M. Boldrini
  • P. M. Whitaker-Azmitia
Original Paper


In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was seen throughout superior temporal cortex (primary auditory cortex), fusiform cortex (face recognition center), pons/midbrain and cerebellum in postmortem brains from ASD patients but not control brains. We found significant increases in both nestin and CD34, which are markers of angiogenesis localized to pericyte cells and endothelial cells, respectively. This labeling profile is indicative of splitting (intussusceptive), rather than sprouting, angiogenesis indicating the blood vessels are in constant flux rather than continually expanding.


Intussusceptive Pericytes Endothelial Nestin CD34 Superior temporal cortex 



NYU Challenge Grant 2014–2015 (Azmitia) and NIMH R01MH083862-05 (Boldrini) provided the necessary support for this work. Dr. Jerzy Wegiel for his invaluable advice and support during this work and also for contributing human postmortem tissue. Dr. Jane Pickett for her encouragement throughout this project and her help in obtaining postmortem tissue from the Autism Tissue Program. Dr. H.R. Zielke for providing postmortem brain tissue from the NICHD brain bank and, in particular, for making available samples from a autism donor who died from serotonin syndrome. Finally, helpful technical work was supplied by Victoria Lee, Amritpal Saini, Hanna Chen, Pooja P Kothari and Gordon Jiang.

Author Contributions

EA participated in all aspects of the study from concept to drafting the manuscript; ZS coordination of the study and performed the measurement; participated in the design and interpretation of the data; performed the statistical analysis; helped to draft the manuscript; MA coordination of the study and performed the measurement; helped to draft the manuscript; MB participated in the design of the study and performed the statistical analysis; PW participated in the design of the study and helped to draft the manuscript. All authors read and approved the final manuscript.

Supplementary material

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  1. Akbari, H. M., Whitaker-Azmitia, P. M., & Azmitia, E. C. (1994). Prenatal cocaine decreases the trophic factor S-100beta and induced microcephaly: Reversal by postnatal 5-HT1A receptor agonist. Neuroscience Letters, 170(1), 141–144.CrossRefPubMedGoogle Scholar
  2. Anderson, G. M. (2002). Genetics of childhood disorders: XLV. Autism, part 4: Serotonin in autism. Journal of American Academy of Child. Adolescent Psychiatry, 41(12), 1513–1516.CrossRefGoogle Scholar
  3. Azmitia, E. C., & Impallomeni, A. (2014). Dynamic brain changes in autism: review of telencephalic structures. In Comprehensive guide to autism (pp 695–716).Google Scholar
  4. Azmitia, E. C., & Nixon, R. (2008). Dystrophic serotonergic axons in neurodegenerative diseases. Brain Research, 27(1217), 185–194.CrossRefGoogle Scholar
  5. Azmitia, E. C., Singh, J. S., Hou, X. P., & Wegiel, J. (2011a). Dystrophic serotonin axons in postmortem brains from young autism patients. Anatomical Record, 294, 1653–1662.CrossRefGoogle Scholar
  6. Azmitia, E. C., Singh, J. S., Whitaker-Azmitia, P. M., et al. (2011b). Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors. Neuropharmacology, 60, 1347–1354.CrossRefPubMedGoogle Scholar
  7. Bandopadhyay, R., Orte, C., Lawrenson, J. G., Reid, A. R., De Silva, S., & Allt, G. (2001). Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. Journal of Neurocytology, 30(1), 35–44.CrossRefPubMedGoogle Scholar
  8. Bigler, E. D., Mortensen, S., Neeley, E. S., Ozonoff, S., Krasny, L., Johnson, M., et al. (2007). Superior temporal gyrus, language function, and autism. Developmental Neuropsychology, 31(2), 217–238.CrossRefPubMedGoogle Scholar
  9. Blatt, G. J. (2012). The neuropathology of autism. Scientifica (Cairo), 2012(2012), 703675.Google Scholar
  10. Boddaert, N., Zilbovicius, M., Philipe, A., Robel, L., Bourgeois, M., Barthélemy, C., et al. (2009). MRI findings in 77 children with non-syndromic autistic disorder. PLoS ONE, 4(2), e4415.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Boldrini, M., Hen, R., Underwood, M. D., Rosoklija, G. B., Dwork, A. J., Mann, J. J., et al. (2012). Hippocampal angiogenesis and progenitor cell proliferation are increased with antidepressant use in major depression. Biological Psychiatry, 72(7), 562–571.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Burri, P. H., Djonov, V. G., & Kurz, H. (2002). Optimality in the developing vascular system: Branching remodeling by means of intussusception as an efficient adaptation mechanism. Developmental Dynamics, 224(4), 391–402.CrossRefPubMedGoogle Scholar
  13. Casanova, M. F., van Kooten, I. A., Switala, A. E., van Engeland, H., Heinsen, H., Steinbusch, H. W., et al. (2006). Minicolumnar abnormalities in autism. Acta Neuropathologica, 112(3), 287–303.CrossRefPubMedGoogle Scholar
  14. Casanova, M. F., El-Baz, A., Mott, M., Mannheim, G., Hassan, H., Fahmi, R., et al. (2009). Reduced gyral window and corpus callosum size in autism: Possible macroscopic correlates of a minicolumnopathy. Journal of Autism and Developmental Disorders, 39(5), 751–764.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Casanova, M. F., El-Baz, A. S., Kamat, S. S., Dombroski, B. A., Khalifa, F., Elnakib, A., et al. (2013). Focal cortical dysplasias in autism spectrum disorders. Acta Neuropathologica Communications, 1(1), 67.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Courchesne, E. (1997). Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism. Current Opinion in Neurobiology, 7(2), 269–278.CrossRefPubMedGoogle Scholar
  17. Courchesne, E., Mouton, P. R., Calhoun, M. E., Semendeferi, K., Ahrens-Barbeau, C., Hallet, M. J., et al. (2011). Neuron number and size in prefrontal cortex of children with autism. Journal of the American Medical Association, 306(18), 2001–2010.CrossRefPubMedGoogle Scholar
  18. Covas, D. T., Panepucci, R. A., Fontes, A. M., Silva, W. A., Orellana, M. D., Freitas, M. C., et al. (2008). Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146 + perivascular cells and fibroblasts. Experimental Hematology, 36, 642–654.CrossRefPubMedGoogle Scholar
  19. De Spiegelaere, W., Cornillie, P., Van den Broeck, W., Plendl, J., & Bahramsoltani, M. (2011). Angiopoietins differentially influence in vitro angiogenesis by endothelial cells of different origin. Clinical Hemorheology Microcirculation, 48, 15–27.PubMedGoogle Scholar
  20. Djonov, V. G., Kurz, H., & Burri, P. H. (2002). Optimality in the developing vascular system: In branching remodeling by means of intussusception as an efficient adaptation mechanism. Developmental Dynamics, 224(4), 391–402.CrossRefPubMedGoogle Scholar
  21. Dore-Duffy, P., Katychev, A., Van Buren, E., & Wang, X. (2006). CNS microvascular pericytes exhibit multipotential stem cell activity. Journal of Cerebral Blood Flow and Metabolism, 26, 613–624.CrossRefPubMedGoogle Scholar
  22. Dore-Duffy, P., Bradley, M., Gow, A., Mehedi, A., Trotter, R., & Wang, X. (2011). Immortalized CNS pericytes are quiescent smooth muscle actin-negative and pluripotent. Microvascular Research, 82(1), 18–27.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Dzietko, M., Derugin, N., Ferriero, D. M., Wendland, M. F., & Vexler, Z. S. (2013). Delayed VEGF treatment enhances angiogenesis and recovery after neonatal focal rodent stroke. Translational Stroke Research, 4, 189–200.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Farahani, R. M., Sarrafpour, B., Simonian, M., Li, Q., & Hunter, N. (2012). Directed glia-assisted angiogenesis in a mature neurosensory structure: Pericytes mediate an adaptive response in human dental pulp that maintains blood-barrier function. Journal of Comparative Neurology, 520(17), 3803–3826.CrossRefPubMedGoogle Scholar
  25. Fatemi, S. H., Earle, J., Halt, A. R., Kirst, D. A., Merz, A., Realmuto, G., et al. (2002). Purkinje cell size is reduced in cerebellum of patients with autism. Cell Molecular Neurobiology, 22(2), 171–175.CrossRefGoogle Scholar
  26. Fatemi, S. H., Reutiman, T. J., Folsom, T. D., Rustan, O. G., Rooney, R. J., & Thuras, P. D. (2014). Downregulation of GABAA receptor protein subunits α6, β2, δ, ε, γ2, θ, and ρ2 in superior frontal cortex of subjects with autism. Journal of Autism and Developmental Disorders, 44(8), 1833–1845.CrossRefPubMedGoogle Scholar
  27. Fraser, R. A., Ellis, E. M., & Stalker, A. L. (1979). Experimental angiogenesis in the chorio-allantoic membrane. Bibliotheca Anatomia, 18, 25–27.Google Scholar
  28. Fung, L. K., Libove, R. A., Phillips, J., Haddad, F., & Hardan, A. Y. (2014). Brief report: An open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. Journal of Autism and Developmental Disorders, 44(11), 2971–2977.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Gerlach, J. C., Over, P., Turner, M. E., Thompson, R. L., Foka, H. G., Chen, W. C., et al. (2012). Perivascular mesenchymal progenitors in human fetal and adult liver. Stem Cells and Development, 21(18), 3258–3269.CrossRefPubMedGoogle Scholar
  30. Goligorsky, M. S., & Salven, P. (2013). Concise review: Endothelial Stem and progenitor cells and their habitats. Stem Cells Translational Medicine, 2(7), 499–504.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Guy, J., Perreault, A., Mottron, L., & Bertone, A. (2015). A systematic examination of early perceptual influences on low-, mid and high-level visual abilities in autism spectrum disorder. Journal of Vision, 15(12), 644. doi: 10.1167/15.12.644.CrossRefPubMedGoogle Scholar
  32. Haar, S., Berman, S., Behrmann, M., & Dinstein, I. (2014). Anatomical abnormalities in autism? Cerebral Cortex, 1–13.Google Scholar
  33. Hellendoorn, A., Wijnroks, L., van Daalen, E., Dietz, C., Buitelaar, J. K., & Leseman, P. (2015). Motor functioning, exploration, visuospatial cognition and language development in preschool children with autism. Research in Developmental Disabilities, 39, 32–42.CrossRefPubMedGoogle Scholar
  34. Hirschi, K. K., & D’Amore, P. A. (1997). Control of angiogenesis by the pericyte: Molecular mechanisms and significance. Experientia Supplementum, 79, 419–428.CrossRefGoogle Scholar
  35. Holthöfer, H., Virtanen, I., Kariniemi, A. L., Hormia, M., Linder, E., & Miettinen, A. (1982). Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Laboratory Investigation, 47(1), 60–66.PubMedGoogle Scholar
  36. Hughes, J. R., & Melyn, M. (2005). EEG and seizures in autistic children and adolescents: Further findings with therapeutic implications. Clinical EEG and Neuroscience, 36(1), 15–20.CrossRefPubMedGoogle Scholar
  37. Hutsler, J. J., & Casanova, M. F. (2015). Cortical construction in autism spectrum disorder: columns, connectivity and the subplate. Neuropathololgy and Applied Neurobiology (in press).Google Scholar
  38. Jacot-Descombes, S., Uppal, N., Wicinski, B., Santos, M., Schmeidler, J., Giannakopoulos, P., et al. (2012). Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism. Acta Neuropathologica, 124(1), 67–79.CrossRefPubMedGoogle Scholar
  39. Jones, K. B., Cottle, K., Bakian, A., Farley, M., Bilder, D., Coon, H., et al. (2015). A description of medical conditions in adults with autism spectrum disorder: A follow-up of the 1980 s Utah/UCLA Autism Epidemiologic Study. Autism (in press).Google Scholar
  40. Kennedy, D. P., Redcay, E., & Courchesne, E. (2006a). Failing to deactivate: Resting functional abnormalities in autism. Proceedings of the National Academy of Sciences of the United States America, 103(21), 8275–8280.CrossRefGoogle Scholar
  41. Kennedy, D. P., Redcay, E., & Courchesne, E. (2006b). Failing to deactivate: Resting functional abnormalities in autism. Proceedings of the National Academy of Sciences of the United States America, 103(21), 8275–8280.CrossRefGoogle Scholar
  42. Keown, C. L., Shih, P., Nair, A., Peterson, N., Mulvey, M. E., & Müller, R. A. (2013). Local functional overconnectivity in posterior brain regions is associated with symptom severity in autism spectrum disorders. Cell Reports, 5(3), 567–572.CrossRefPubMedGoogle Scholar
  43. Kulesza Jr., R. J., Lukose, R., & Stevens, L. V. (2011). Malformation of the human superior olive in autistic spectrum disorders. Brain Research, 1367:360–371. (significant decrease in the number of SOC neurons in the autistic brain).Google Scholar
  44. Kurth, F., Narr, K. L., Woods, R. P., O’Neill, J., Alger, J. R., Caplan, R., et al. (2011). Diminished gray matter within the hypothalamus in autism disorder: A potential link to hormonal effects? Biology Psychiatry, 70(3), 278–282.CrossRefGoogle Scholar
  45. Lam, K. S., Aman, M. G., & Arnold, L. E. (2006). Neurochemical correlates of autistic disorder: A review of the literature. Research on Developmental Disabilities, 27(3), 254–289.CrossRefGoogle Scholar
  46. Lendahl, U., Zimmerman, L. B., & McKay, R. D. (1990). CNS stem cells express a new class of intermediate filament protein. Cell, 60(4), 585–595.CrossRefPubMedGoogle Scholar
  47. Leyfer, O. T., Folstein, S. E., Bacalman, S., Davis, N. O., Dinh, E., Morgan, J., et al. (2006). Comorbid psychiatric disorders in children with autism: Interview development and rates of disorders. Journal of Autism and Developmental Disorders, 36(7), 849–861.CrossRefPubMedGoogle Scholar
  48. Maenner, M. J., Arneson, C. L., Levy, S. E., Kirby, R. S., Nicholas, J. S., Durkin, M. S., et al. (2012). Brief report: Association between behavioral features and gastrointestinal problems among children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 42(7), 1520–1525.CrossRefPubMedGoogle Scholar
  49. Marchi, N., & Lerner-Natoli, M. (2013). Cerebrovascular remodeling and epilepsy. Neuroscientist, 19(3), 304–312.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Marcon, J., Gagliardi, B., Balosso, S., Maroso, M., Noe, F., Morin, M., et al. (2009). Age-dependent vascular changes induced by status epilepticus in rat forebrain: Implications for epileptogenesis. Neurobiology of Disease, 34(1), 121–132.CrossRefPubMedGoogle Scholar
  51. Michalczyk, K., & Ziman, M. (2005). Nestin structure and predicted function in cellular cytoskeletal organization. Histology and Histopathology, 20(2), 665–671.PubMedGoogle Scholar
  52. Morin-Brureau, M., Rigau, V., & Lerner-Natoli, M. (2012). Why and how to target angiogenesis in focal epilepsies. Epilepsia, 53(Supplement s6), 64–68.CrossRefPubMedGoogle Scholar
  53. Mulligan, C. K., & Trauner, D. A. (2014). Incidence and behavioral correlates of epileptiform abnormalities in autism spectrum disorders. Journal of Autism and Developmental Disorders, 44, 452–458.CrossRefPubMedGoogle Scholar
  54. O’Connor, K., & Kirk, I. (2008). Brief report: atypical social cognition and social behaviours in autism spectrum disorder: A different way of processing rather than an impairment. Journal of Autism and Developmental Disorders, 38(10), 1989–1997.CrossRefPubMedGoogle Scholar
  55. Ozen, S., Darcan, S., Bayindir, P., Karasulu, E., Simsek, D. G., & Gurler, T. (2012). Effects of pesticides used in agriculture on the development of precocious puberty. Environmental Monitoring and Assessment, 184(7), 4223–4232.CrossRefPubMedGoogle Scholar
  56. Peichev, M., Naiyer, A. J., Pereira, D., Zhu, Z., Lane, W. J., Williams, M., et al. (2000). Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood, 95(3), 952–958.PubMedGoogle Scholar
  57. Perez Velazquez, J. L., Barcelo, F., Hung, Y., Leshchenko, Y., Nenadovic, V., Belkas, J., et al. (2009). Decreased brain coordinated activity in autism spectrum disorders during executive tasks: Reduced long-range synchronization in the fronto-parietal networks. International Journal of Psychophysiology, 73(3), 341–349.CrossRefPubMedGoogle Scholar
  58. Peters, M. A., Walenkamp, A. M., Kema, I. P., Meijer, C., de Vries, E. G., & Oosting, S. F. (2014). Dopamine and serotonin regulate tumor behavior by affecting angiogenesis. Drug Resistance Updates, 17(4–6), 96–104.CrossRefPubMedGoogle Scholar
  59. Poole, D., Gowen, E., Warren, P. A., & Poliakoff, E. (2015). Investigating visual–tactile interactions over time and space in adults with autism. Journal of Autism and Developmental Disorders, 45(10), 3316–3326.CrossRefPubMedGoogle Scholar
  60. Rigau, V., Morin, M., Rousset, M. C., de Bock, F., Lebrun, A., Coubes, P., et al. (2007). Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy. Brain, 130(7), 1942–1956.CrossRefPubMedGoogle Scholar
  61. Rodier, P. M., Ingram, J. L., Tisdale, B., Nelson, S., & Romano, J. (1996). Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. Journal of Comparative Neurology, 370(2), 247–261.CrossRefPubMedGoogle Scholar
  62. Romariz, S. A., Garcia, K. de O., Paiva, D. de S., Bittencourt, S., Covolan, L., Mello, L. E., et al. (2014). Articipation of bone marrow-derived cells in hippocampal vascularization after status epilepticus. Seizure, 23, 386-389.Google Scholar
  63. Rumsey, J. M., & Ernst, M. (2000). Functional neuroimaging of autistic disorders. Mental Retardation and Developmental Disabilities Research Reviews, 6(3), 171–179.CrossRefPubMedGoogle Scholar
  64. Rumsey, J. M., Duara, R., Grady, C., Rapoport, J. L., Margolin, R. A., Rapoport, S. I., et al. (1985). Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography. Archives of General Psychiatry, 42(5), 448–455.CrossRefPubMedGoogle Scholar
  65. Sakurai, M., Morita, T., Takeuchi, T., & Shimada, A. (2013). Relationship of angiogenesis and microglial activation to seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy. American Journal of Veterinary Research, 74(5), 763–770.CrossRefPubMedGoogle Scholar
  66. Seal, B. C., & Bonvillian, J. D. (1997). Sign language and motor functioning in students with autistic disorder. Journal of Autism and Developmental Disorders, 27(4), 437–466.CrossRefPubMedGoogle Scholar
  67. Siegel, B. V, Jr, Asarnow, R., Tanguay, P., Call, J. D., Abel, L., Ho, A., et al. (1992). Regional cerebral glucose metabolism and attention in adults with a history of childhood autism. Journal of Neuropsychiatry and Clinical Neurosciences, 4(4), 406–414.CrossRefPubMedGoogle Scholar
  68. Simonoff, E., Pickles, A., Charman, T., Chandler, S., Loucas, T., & Baird, G. (2008). Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample. Journal of American Academy of Child & Adolescent Psychiatry, 47(8), 921–929.CrossRefGoogle Scholar
  69. Stiegler, L., & Davis, R. (2010). Understanding sound sensitivity in individuals with autism spectrum disorders. Focus on Autism and Other Developmental, 20(10), 1–9.Google Scholar
  70. Supekar, K., Uddin, L. Q., Khouzam, A., Phillips, J., Gaillard, W. D., Kenworthy, L. E., et al. (2013). Brain hyperconnectivity in children with autism and its links to social deficits. Cell Reports, 5(3), 738–747.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Thabet, E. M. (2014). Ocular vestibular evoked myogenic potentials n10 response in autism spectrum disorders children with auditory hypersensitivity: An indicator of semicircular canal dehiscence. European Archives of Oto-Rhino-Laryngology, 271(5), 1283–1288.CrossRefPubMedGoogle Scholar
  72. Thanabalasundaram, G., Arumalla, N., Tailor, H. D., & Khan, W. S. (2011). Regulation of differentiation of mesenchymal stem cells into musculoskeletal cells. Current Stem Cell Research Therapy, 7(2), 95–102.CrossRefGoogle Scholar
  73. Toribatake, Y., Tomita, K., Kawahara, N., Baba, H., Ohnari, H., & Tanaka, S. (1997). Regulation of vasomotion of arterioles and capillaries in the cat spinal cord: Role of alpha actin and endothelin-1. Spinal Cord, 35(1), 26–32.CrossRefPubMedGoogle Scholar
  74. Tuchman, R. (2013). Autism and social cognition in epilepsy: Implications for comprehensive epilepsy care. Current Opinion in Neurology, 26, 214–218.CrossRefPubMedGoogle Scholar
  75. Uppal, N., Wicinski, B., Buxbaum, J. D., Heinsen, H., Schmitz, C., & Hof, P. R. (2014). Neuropathology of the anterior midcingulate cortex in young children with autism. Journal of Neuropathology and Experimental Neurology, 73(9), 891–902.CrossRefPubMedGoogle Scholar
  76. Valvo, G., Baldini, S., Retico, A., Rossi, G., Tancredi, R., Ferrari, A.R., et al. (2015). Temporal lobe connects regression and macrocephaly to autism spectrum disorders. European Child and Adolescent Psychiatry (in press).Google Scholar
  77. Van Kooten, I. A., Palmen, S. J., von Cappeln, P., Steinbusch, H. W., Korr, H., Heinsenm, H., et al. (2008). Neurons in the fusiform gyrus are fewer and smaller in autism. Brain, 131(4), 987–999.CrossRefPubMedGoogle Scholar
  78. Ventola, P. E., Oosting, D., Anderson, L. C., & Pelphrey, K. A. (2013). Brain mechanisms of plasticity in response to treatments for core deficits in autism. Progress in Brain Research, 207, 255–272.CrossRefPubMedGoogle Scholar
  79. Warner-Schmidt, J. L., & Duman, R. S. (2007). VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proceedings of the National Academy of Science USA, 104(11), 4647–4652.CrossRefGoogle Scholar
  80. Wegiel, J., Kuchna, I., Nowicki, K., Imaki, H., Wegiel, J., Marchi, E., et al. (2010). The neuropathology of autism: Defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathologica, 119(6), 755–770.CrossRefPubMedPubMedCentralGoogle Scholar
  81. Wegiel, J., Kuchna, I., Nowicki, K., Imaki, H., Wegiel, J., Ma, S. Y., et al. (2013). Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism. Brain Research, 28(1512), 106–122.CrossRefGoogle Scholar
  82. Whitaker-Azmitia, P. M. (2005). Behavioral and cellular consequences of increasing serotonergic activity during brain development: A role in autism? International Journal of Developmental Neuroscience, 23(1), 75–83.CrossRefPubMedGoogle Scholar
  83. Whyte, E., Elbich, D., Behrmann, M., Minshew, N., & Scherf, K. S. (2015). Altered functional connectivity in the core and extended face-processing network in adolescents with autism. Journal of Vision, 15(12), 1209.CrossRefPubMedGoogle Scholar
  84. Xiao, Z., Qiu, T., Ke, X., Xiao, X., Xiao, T., Liang, F., et al. (2014). Autism spectrum disorder as early neurodevelopmental disorder: Evidence from the brain imaging abnormalities in 2–3 years old toddlers. Journal of Autism and Developmental Disorders, 44(7), 1633–1640.CrossRefPubMedPubMedCentralGoogle Scholar
  85. Zengin, E., Chalajour, F., Gehling, U. M., Ito, W. D., Treede, H., Lauke, H., et al. (2006). Vascular wall resident progenitor cells: A source for postnatal vasculogenesis. Development, 133(8), 1543–1551.CrossRefPubMedGoogle Scholar
  86. Zhang, Z. G., Zhang, L., Tsang, W., Soltanian-Zadeh, H., Morris, D., Zhang, R., et al. (2002). Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia. Journal Cerebral Blood Flow and Metabolism, 22, 379–392.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • E. C. Azmitia
    • 1
    Email author
  • Z. T. Saccomano
    • 1
  • M. F. Alzoobaee
    • 1
  • M. Boldrini
    • 2
    • 3
  • P. M. Whitaker-Azmitia
    • 4
  1. 1.Departments of Biology and PsychiatryNew York UniversityNew YorkUSA
  2. 2.Division of Molecular Imaging and NeuropathologyNew York State Psychiatric InstituteNew YorkUSA
  3. 3.Department of PsychiatryColumbia UniversityNew YorkUSA
  4. 4.Departments of Psychology Program in Integrative Neuroscience, and PsychiatryStony Brook UniversityStony BrookUSA

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