Mouse hippocampal organotypic tissue cultures exposed to in vitro "ischemia" show selective and delayed CA1 damage that is aggravated by glucose.

Abstract

Oxygen and glucose deprivation (OGD) in cell cultures is generally studied in a medium, such as artificial cerebrospinal fluid (CSF), with an ion composition similar to that of the extracellular fluid of the normal brain (2 to 4 mmol/L K+, 2 to 3 mmol/L Ca2+; pH 7.4). Because the distribution of ions across cell membranes dramatically shifts during ischemia, the authors exposed mouse organotypic hippocampal tissue cultures to OGD in a medium, an ischemic cerebrospinal fluid, with an ion composition similar to the extracellular fluid of the brain during ischemia (70 mmol/L K+, 0.3 mmol/L Ca2+; pH 6.8). In ischemic CSF, OGD induced a selective and delayed cell death in the CA1 region, as assessed by propidium iodide uptake. Cell death was glutamate receptor dependent since blockade of the N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors mitigated cell damage. Hyperglycemia aggravates ischemic brain damage whereas glucose in artificial CSF prevents oxygen deprivation-induced damage. The authors demonstrate that glucose in ischemic CSF significantly exacerbates cell damage after oxygen deprivation. This new model of "ischemia" can be useful in future studies of the mechanisms and treatment of ischemic cell death, including studies using genetically modified mice.

• Authors: Anna Rytter, Tobias Cronberg, Fredrik Asztély, Sailasree Nemali, Tadeusz Wieloch
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 23 Issue 1 Pg. 23-33 (Jan 2003) ISSN: 0271-678X [Print] United States
• PMID: 12500088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Antagonists
• Ions
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• Dizocilpine Maleate
• Hydrogen
• Glucose
• Potassium
• Calcium

Topics

• Animals
• Brain Ischemia (metabolism, pathology, physiopathology)
• Calcium (metabolism)
• Cerebrospinal Fluid (metabolism)
• Culture Techniques (methods)
• Dizocilpine Maleate (pharmacology)
• Electrophysiology
• Excitatory Amino Acid Antagonists (pharmacology)
• Glucose (deficiency, pharmacology)
• Hippocampus (drug effects, metabolism, pathology, physiopathology)
• Hydrogen (metabolism)
• Hypoxia (pathology)
• Ions
• Mice
• Mice, Inbred BALB C
• Potassium (metabolism)
• Receptors, AMPA (antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)