Dataset Information

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 ?-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.

SUBMITTER: Farago N

PROVIDER: S-EPMC4972952 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Human neuronal changes in brain edema and increased intracranial pressure.

Faragó Nóra N Kocsis Ágnes Katalin ÁK Braskó Csilla C Lovas Sándor S Rózsa Márton M Baka Judith J Kovács Balázs B Mikite Katalin K Szemenyei Viktor V Molnár Gábor G Ozsvár Attila A Oláh Gáspár G Piszár Ildikó I Zvara Ágnes Á Patócs Attila A Barzó Pál P Puskás László G LG Tamás Gábor G

Acta neuropathologica communications 20160804 1

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 elect ...[more]

PMID: 27487831

Similar Datasets

Project description:BackgroundRepeated invasive intracranial pressure (ICP) monitoring is desirable because many neurosurgical pathologies are associated with elevated ICP. On the other hand, it could become a risk for children to repeat sedation, anesthesia, or radiation exposure. As a non-invasive method, measurements of optic nerve sheath diameter (ONSD) has been revealed to accurately predict increased ICP. However, no studies have indicated a relationship among age, brain, and ventricular parameters in normal children, nor a prediction of increased ICP with artificial intelligence.Methods and findingsThis study enrolled 400 normal children for control and 75 children with signs of increased ICP between 2009 and 2019. Measurements of the parameters including ONSD on CT were obtained. A supervised machine learning was applied to predict suspected increased ICP based on CT measurements. A linear correlation was shown between ln(age) and mean ONSD (mONSD) in normal children, revealing mONSD = 0.36ln(age)+2.26 (R2 = 0.60). This study revealed a linear correlation of mONSD measured on CT with ln(age) and the width of the brain, not the width of the ventricles in 400 normal children based on the univariate analyses. Additionally, the multivariate analyses revealed minimum bicaudate nuclei distance was also associated with mONSD. The results of the group comparison between control and suspected increased ICP revealed a statistical significance in mONSD and the width of the ventricles. The study indicated that supervised machine learning application could be applied to predict suspected increased ICP in children, with an accuracy of 94% for training, 91% for test.ConclusionsThis study clarified three issues regarding ONSD and ICP. Mean ONSD measured on CT was correlated with ln(age) and the width of the brain, not the width of the ventricles in 400 normal children based on the univariate analyses. The multivariate analyses revealed minimum bicaudate nuclei distance was also associated with mONSD. Mean ONSD and the width of ventricles were statistically significant in children with signs of elevated ICP. Finally, the study showed that machine learning could be used to predict children with suspected increased ICP.

Dataset Information

Human neuronal changes in brain edema and increased intracranial pressure.

Publications

Human neuronal changes in brain edema and increased intracranial pressure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets