This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McKinney, J.S. Articles by Ellis, E.F. Search for Related Content PubMed PubMed Citation Articles by McKinney, J.S. Articles by Ellis, E.F.

(Stroke. 1996;27:934-940.)
© 1996 American Heart Association, Inc.

Articles

Stretch-Induced Injury of Cultured Neuronal, Glial, and Endothelial Cells

Effect of Polyethylene Glycol–Conjugated Superoxide Dismutase

J.S. McKinney, BS; K.A. Willoughby, BS; S. Liang, BS E.F. Ellis, PhD

From the Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University (Richmond).

Correspondence to Dr Earl F. Ellis, Box 980613, MCV Station, Richmond, VA 23298-0613.

Background and Purpose There is abundant evidence that after in vivo traumatic brain injury, oxygen radicals contribute to changes in cerebrovascular structure and function; however, the cellular source of these oxygen radicals is not clear. The purpose of these experiments was to use a newly developed in vitro tissue culture model to elucidate the effect of strain, or stretch, on neuronal, glial, and endothelial cells and to determine the effect of the free radical scavenger polyethylene glycol–conjugated superoxide dismutase (PEG-SOD; pegorgotein, Dismutec) on the response of each cell type to trauma.

Methods Rat brain astrocytes, neuronal plus glial cells, and aortic endothelial cells were grown in cell culture wells with 2-mm-thick silastic membrane bottoms. A controllable, 50-millisecond pressure pulse was used to transiently deform the silastic membrane and thus stretch the cells. Injury was assessed by quantifying the number of cells that took up the normally cell-impermeable dye propidium iodide. Some cultures were pretreated with 100 to 300 U/mL PEG-SOD.

Results Increasing degrees of deformation produced increased cell injury in astrocytes, neuronal plus glial cultures, and aortic endothelial cells. By 24 hours after injury, all cultures showed evidence of repair as demonstrated by cells regaining their capacity to exclude propidium iodide. Compared with astrocytes or neuronal plus glial cultures, endothelial cells were much more resistant to stretch-induced injury and more quickly regained their capacity to exclude propidium iodide. PEG-SOD had no effect on the neuronal or glial response to injury but reduced immediate posttraumatic endothelial cell dye uptake by 51%.

Conclusions These studies further document the utility of the model for studying cell injury and repair and further support the vascular endothelial cell as a site of free radical generation and radical-mediated injury. On the assumption that, like aortic endothelial cells, stretch-injured cerebral endothelial cells also produce oxygen radicals, our results further suggest the endothelial cell as a site of therapeutic action of free radical scavengers after traumatic brain injury.

Key Words: brain injuries • cerebral blood flow • free radicals

This article has been cited by other articles:

				J. D. Bell, J. Ai, Y. Chen, and A. J. Baker Mild in vitro trauma induces rapid Glur2 endocytosis, robustly augments calcium permeability and enhances susceptibility to secondary excitotoxic insult in cultured Purkinje cells Brain, October 1, 2007; 130(10): 2528 - 2542. [Abstract] [Full Text] [PDF]

				J. T. Neary, Y. Kang, K. A. Willoughby, and E. F. Ellis Activation of Extracellular Signal-Regulated Kinase by Stretch-Induced Injury in Astrocytes Involves Extracellular ATP and P2 Purinergic Receptors J. Neurosci., March 15, 2003; 23(6): 2348 - 2356. [Abstract] [Full Text] [PDF]

				J. E. Slemmer, E. J. T. Matser, C. I. De Zeeuw, and J. T. Weber Repeated mild injury causes cumulative damage to hippocampal cells Brain, December 1, 2002; 125(12): 2699 - 2709. [Abstract] [Full Text] [PDF]

				P. B. Goforth, E. F. Ellis, and L. S. Satin Enhancement of AMPA-Mediated Current after Traumatic Injury in Cortical Neurons J. Neurosci., September 1, 1999; 19(17): 7367 - 7374. [Abstract] [Full Text] [PDF]

				D. G. Binion, S. Fu, K. S. Ramanujam, Y. C. Chai, R. A. Dweik, J. A. Drazba, J. G. Wade, N. P. Ziats, S. C. Erzurum, and K. T. Wilson iNOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion Am J Physiol Gastrointest Liver Physiol, September 1, 1998; 275(3): G592 - G603. [Abstract] [Full Text] [PDF]

				R. Schmid-Elsaesser, S. Zausinger, E. Hungerhuber, N. Plesnila, A. Baethmann, and H.-J. Reulen Superior Neuroprotective Efficacy of a Novel Antioxidant (U-101033E) With Improved Blood-Brain Barrier Permeability in Focal Cerebral Ischemia Stroke, October 1, 1997; 28(10): 2018 - 2024. [Abstract] [Full Text]

				L. Zhang, B. A. Rzigalinski, E. F. Ellis, and L. S. Satin Reduction of Voltage-Dependent Mg2+ Blockade of NMDA Current in Mechanically Injured Neurons Science, December 13, 1996; 274(5294): 1921 - 1923. [Abstract] [Full Text]

				J. T. Weber, B. A. Rzigalinski, and E. F. Ellis Traumatic Injury of Cortical Neurons Causes Changes in Intracellular Calcium Stores and Capacitative Calcium Influx J. Biol. Chem., January 12, 2001; 276(3): 1800 - 1807. [Abstract] [Full Text] [PDF]