Citation

Smith ME, Eskandari R. J. Neurosci. Methods 2017; 293: 247-253.

Affiliation

Department of Neurosurgery, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: eskandar@musc.edu.

Copyright

(Copyright © 2017, Elsevier Publishing)

DOI

10.1016/j.jneumeth.2017.10.004

PMID

28993205

Abstract

BACKGROUND: Elevated intracranial pressure (ICP) accompanying a number of neurological emergencies is poorly understood, and lacks a model to determine cellular pathophysiology. This limits our ability to identify cellular and molecular biomarkers associated with the pathological progression from physiologic to pathologic ICP. NEW METHOD: We developed an ex vivo model of pressure-induced brain injury, which combines 3D neural cell cultures and a newly developed Pressure Controlled Cell Culture Incubator (PC(3)I). Human astrocytes and neurons maintained in 3D peptide-conjugated alginate hydrogels were subjected to pressures that mimic both physiologic and pathologic levels of ICP for up to 48hours to evaluate the earliest impacts of isolated pressure on cellular viability and quantify early indicators of pressure-induced cellular injury.

RESULTS: Compared to control cell cultures grown under physiologic pressure, sustained pathologic pressure exposure increased the release of intracellular ATP in a cell-specific manner. Eighteen hours of sustained pressure resulted in increased ATP release from neurons but not astrocytes. COMPARISON WITH EXISTING METHODS: Cell culture incubators maintain cultures at normal atmospheric pressure. Based on multiple literature searches, we are not aware of any other cell culture incubator systems that modify the pressure at which primary CNS cells are maintained.

CONCLUSION: This model simulates the clinical features of elevated ICP encountered in patients with hydrocephalus, and provides a first estimate of the pathological signaling encountered during the earliest perid of progression in neonatal hydrocephalus. This model should provide a means to better understand the pathological biomarkers associated with the earliest stages of elevated ICP.

Copyright © 2017 Elsevier B.V. All rights reserved.

Language: en

Keywords

3D model; Hydrocephalus; engineered neural tissue; pressure injury; traumatic brain injury