Brain study may lead to improved epilepsy treatments

Using isolated brain capillaries from mice and rats and an animal model of epilepsy, the researchers found that glutamate, a neurotransmitter released when neurons fire during seizures, turns on a signaling pathway that activates cyclooxygenase-2 (COX-2), causing increased synthesis of P-glycoprotein in these experiments. Increased transporter expression was abolished in COX-2 knockout mice or by COX-2 inhibitors. It has yet to be shown in animals or patients that targeting COX-2 will reduce seizure frequency or increase the effectiveness of anti-epileptic drugs.

"These findings provide insight into one mechanism that underlies drug resistance in epilepsy and possibly other central nervous system disorders," said Bjoern Bauer, Ph.D., lead author on the publication. "Targeting blood-brain barrier signals that increase P-glycoprotein expression rather than the transporter itself suggests a promising way to improve the effectiveness of drugs that are used to treat epilepsy, though more research is needed before new therapies can be developed.”

The primary mission of the National Institute of Environmental Health Sciences (http://www.niehs.nih.gov) (NIEHS), one of 27 Institutes and Centers at the National Institutes of Health, is to reduce the burden of human illness and disability by understanding how the environment influences the development and progression of human disease. For additional information, visit the NIEHS Web site at http://www.niehs.nih.gov/.

The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Reference: Bauer B, Hartz AM, Pekcec A, Toellner K, Miller DS, Potschka H. Seizure-Induced Upregulation of P-glycoprotein at the Blood-Brain Barrier through Glutamate and COX-2 Signaling. Molecular Pharmacology. 2007 Dec 19 [Epub ahead of print] doi:10.1124/mol.107.041210.