Protection against hypoxia-induced blood-brain barrier disruption: changes in intracellular calcium.

Abstract

Tissue damage after stroke is partly due to disruption of the blood-brain barrier (BBB). Little is known about the role of calcium in modulating BBB disruption. We investigated the effect of hypoxic and aglycemic stress on BBB function and intracellular calcium levels. Bovine brain microvessel endothelial cells were treated with A-23187 to increase intracellular calcium without hypoxia or treated with a calcium chelator (BAPTA) or calcium channel blockers (nifedipine or SKF-96365) and 6 h of hypoxia. A-23187 alone did not increase paracellular permeability. Hypoxia increased intracellular calcium, and hypoxia or hypoxia-aglycemia increased paracellular permeability. Treatment with nifedipine and SKF-96365 increased intracellular calcium under normoglycemic conditions, instead of blocking calcium influx, and was protective against hypoxia-induced BBB disruption under normoglycemia. Protection by nifedipine and SKF-96365 was not due to antioxidant properties of these compounds. These data indicate that increased intracellular calcium alone is not enough to disrupt the BBB. However, increased intracellular calcium after drug treatment and hypoxia suggests a potential mechanism for these drugs in BBB protection; nifedipine and SKF-96365 plus hypoxic stress may trigger calcium-mediated signaling cascades, altering BBB integrity.

• Authors: Rachel C Brown, Karen S Mark, Richard D Egleton, Thomas P Davis
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 286 Issue 5 Pg. C1045-52 (May 2004) ISSN: 0363-6143 [Print] United States
• PMID: 15075203 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antioxidants
• Calcium Channel Blockers
• Chelating Agents
• Imidazoles
• Ionophores
• Calcimycin
• Egtazic Acid
• 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
• Nifedipine
• 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
• Calcium

Topics

• Animals
• Antioxidants (pharmacology)
• Blood-Brain Barrier (drug effects)
• Calcimycin (pharmacology)
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Cattle
• Cell Membrane Permeability (drug effects)
• Cells, Cultured
• Chelating Agents (pharmacology)
• Egtazic Acid (analogs & derivatives, pharmacology)
• Endothelium, Vascular (drug effects, metabolism)
• Hypoxia (metabolism, physiopathology)
• Imidazoles (pharmacology)
• Intracellular Fluid (metabolism)
• Ionophores (pharmacology)
• Nifedipine (pharmacology)