title: Human neuronal changes in brain edema and increased intracranial pressure.
abstract: Functional and molecular changes associated with pathophysiological conditions are relatively easily detected based on tissue samples collected from patients. Population specific cellular responses to disease might remain undiscovered in samples taken from organs formed by a multitude of cell types. This is particularly apparent in the human cerebral cortex composed of a yet undefined number of neuron types with a potentially different involvement in disease processes. We combined cellular electrophysiology, anatomy and single cell digital PCR in human neurons identified in situ for the first time to assess mRNA expression and corresponding functional changes in response to edema and increased intracranial pressure. In single pyramidal cells, mRNA copy numbers of AQP1, AQP3, HMOX1, KCNN4, SCN3B and SOD2 increased, while CACNA1B, CRH decreased in edema. In addition, single pyramidal cells increased the copy number of AQP1, HTR5A and KCNS1 mRNAs in response to increased intracranial pressure. In contrast to pyramidal cells, AQP1, HMOX1and KCNN4 remained unchanged in single cell digital PCR performed on fast spiking cells in edema. Corroborating single cell digital PCR results, pharmacological and immunohistochemical results also suggested the presence of KCNN4 encoding the α-subunit of KCa3.1 channels in edema on pyramidal cells, but not on interneurons. We measured the frequency of spontaneous EPSPs on pyramidal cells in both pathophysiological conditions and on fast spiking interneurons in edema and found a significant decrease in each case, which was accompanied by an increase in input resistances on both cell types and by a drop in dendritic spine density on pyramidal cells consistent with a loss of excitatory synapses. Our results identify anatomical and/or physiological changes in human pyramidal and fast spiking cells in edema and increased intracranial pressure revealing cell type specific quantitative changes in gene expression. Some of the edema/increased intracranial pressure modulated and single human pyramidal cell verified gene products identified here might be considered as novel pharmacological targets in cell type specific neuroprotection.
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.|Laboratory of Functional Genomics, Department of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.|Avidin Ltd., Alsó kikötő sor 11, Szeged, H-6726, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Faragó
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Ágnes Katalin
authors.initials: ÁK
authors.lastname: Kocsis
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Braskó
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Lovas
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Rózsa
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Judith
authors.initials: J
authors.lastname: Baka
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Kovács
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Mikite
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Szemenyei
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Molnár
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Ozsvár
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Gáspár
authors.initials: G
authors.lastname: Oláh
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Piszár
authors.affiliation: Laboratory of Functional Genomics, Department of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Zvara
authors.affiliation: MTA Lendület Hereditary Endocrine Tumors Research Group, Semmelweis University, Szentkirályi u. 46, Budapest, H-1088, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Patócs
authors.affiliation: Department of Neurosurgery, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Barzó
authors.affiliation: Laboratory of Functional Genomics, Department of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.|Avidin Ltd., Alsó kikötő sor 11, Szeged, H-6726, Hungary.
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.affiliation: MTA-SZTE Research Group for Cortical Microcircuits of the Hungarian Academy of Sciences, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary. gtamas@bio.u-szeged.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Tamás
mesh_terms: D000328:Adult; D001929:Brain Edema / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation; D066128:Gray Matter / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D019586:Intracranial Hypertension / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007427:Intracranial Pressure / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D012333:RNA, Messenger