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.

Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential

“…However, direct osmotically-driven water influx is not likely to be a major pathway, because central neurons lack aquaporins [15,90,102,121,122]. While some aquaporin genes are up-regulated in neurons after brain edema, their functional role in the development of cytotoxic edema is much less clear [132]. Movement of water via CCCs is observed in conditions that induce cell/dendritic edema including spreading depression [133,134].…”

Neurophysiological predictors of aphasia recovery in patients with large left-hemispheric infarction

“…During the first 7 days, patients with LHI consistently suffer from different extents of brain edema and overall metabolic depression, which dampen neural processes and affect brain electrical activity. [19] In patients with effective compensation via enhanced branch circulation after vascular occlusion, brain edema is less severe, and neurofunction can be restored after the edema period. However, in patients with inadequate branch compensation, excessive perfusion or hemorrhagic transformation after recanalization, brain function cannot recover or even deteriorate.…”

Intelligent image-based in situ single-cell isolation

“…: 4458095), and nuclease-free water (3 μl) were mixed to obtain a total volume of 20 μl, and the mixture was evenly distributed on four subarrays (256 nanocap­illary holes) of an OpenArray plate by using the OpenArray autoloader. Processing of the OpenArray slide, cycling in the OpenArray NT cycler, and data analysis were done as previously described 22 . For our dPCR protocol amplification, reactions having CT values less than 23 or greater than 33 were considered primer dimers or background signals, respectively, and excluded from the data set.…”