title: An in vitro model for investigating human autologous neuronal-astrocyte and immune cell interactions underlying neurodegenerative and immunosuppressive processes in neuropathy.
abstract: Primary mixed neuronal-astrocytic cultures were established from human brain tissues from elective surgical procedures and maintained in vitro for over 21 days. The majority of cells (a) expressed morphological and cytoskeletal markers of differentiated neurons (MAP2a&b; Tau) or astrocytes (GFAP) in anticipated proportion (1:2), and (b) regenerated synaptic connections and neural-astrocytic associations. Co-cultures with autologous blood leukocytes established that alterations in the viability (by Annexin V/PI) of brain and immune cells over 3 days were indicative of neurodegenerative or immunosuppressive processes. During co-culture, B-cells (CD19+) remained largely unaffected while T-lymphocytes (CD3+) and monocytes (CD14+) declined, consistent with immunosuppressive process. Indications of immunosuppression were not observed when immune cells were maintained in free of neural cells medium collected from neuro-cultures. Decline in brain cell viability in neuro-immune co-cultures may be associated with density of activated monocytes (HLA-DR+/CD14+), consistent with neurodegenerative process. Our findings, though preliminary and associated with significant variability between individuals, establish an approach to investigate neuroimmune pathology in humans.
authors.affiliation: Laboratory of Surgical Research, First Department of Propaedeutic Surgery, National Kapodistrian University of Athens, Athens, Greece. Electronic address: aderventz@med.uoa.gr.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Derventzi
authors.affiliation: Laboratory of Surgical Research, First Department of Propaedeutic Surgery, National Kapodistrian University of Athens, Athens, Greece.
authors.forename: Muarilena
authors.initials: M
authors.lastname: Nikolopoulou
authors.affiliation: Laboratory of Surgical Research, First Department of Propaedeutic Surgery, National Kapodistrian University of Athens, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Apostolou
authors.affiliation: Laboratory of Surgical Research, First Department of Propaedeutic Surgery, National Kapodistrian University of Athens, Athens, Greece.
authors.forename: Agapi
authors.initials: A
authors.lastname: Kataki
authors.affiliation: Laboratory of Surgical Research, First Department of Propaedeutic Surgery, National Kapodistrian University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Bakopoulos
authors.affiliation: Department of Neurosurgery, 'KAT' National Hospital, Athens, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Androulis
authors.affiliation: Neurologic Clinic, 'Aeginiteio' Hospital, National Kapodistrian University of Athens, Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Kilidireas
authors.affiliation: First Department of Propaedeutic Surgery, 'Hippocration' Hospital, National Kapodistrian University of Athens, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Zografos
authors.affiliation: Laboratory of Surgical Research, First Department of Propaedeutic Surgery, National Kapodistrian University of Athens, Athens, Greece; First Department of Propaedeutic Surgery, 'Hippocration' Hospital, National Kapodistrian University of Athens, Athens, Greece.
authors.forename: Manousos M
authors.initials: MM
authors.lastname: Konstadoulakis
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D001921:Brain / Q000166:cytology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002450:Cell Communication; D002470:Cell Survival; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003599:Cytoskeleton / Q000648:ultrastructure; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007249:Inflammation / Q000473:pathology; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009410:Nerve Degeneration / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D015213:Neuroimmunomodulation / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D061251:Primary Cell Culture; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014947:Wounds and Injuries / Q000097:blood / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins
keywords: Autologous neuro–immune co-cultures; Primary human adult neuronal and astrocytic cultures