Navigation Links
Brain study may lead to improved epilepsy treatments
Date:4/14/2008

Using a rodent model of epilepsy, researchers found one of the bodys own neurotransmitters released during seizures, glutamate, turns on a signaling pathway in the brain that increases production of a protein that could reduce medication entry into the brain. Researchers say this may explain why approximately 30 percent of patients with epilepsy do not respond to antiepileptic medications. The study, conducted by researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, and the University of Minnesota College of Pharmacy and Medical School, in collaboration with Heidrun Potschkas laboratory at Ludwig-Maximilians-University in Munich, Germany, is available online and will appear in the May 2008, issue of Molecular Pharmacology.

Our work identifies the mechanism by which seizures increase production of a drug transport protein in the blood brain barrier, known as P-glycoprotein, and suggests new therapeutic targets that could reduce resistance, said David Miller, Ph.D., a principal investigator in the NIEHS Laboratory of Pharmacology and co-author on the paper.

The blood-brain barrier (BBB), which resides in brain capillaries, is a limiting factor in treatment of many central nervous system disorders. It is altered in epilepsy so that it no longer permits free passage of administered antiepileptic drugs into the brain. Miller explained that P-glycoprotein forms a functional barrier in the BBB that protects the brain by limiting access of foreign chemicals.

The problem is that the protein does not distinguish well between neurotoxicants and therapeutic drugs, so it can often be an obstacle to the treatment of a number of diseases, including brain cancer, Miller said. Increased levels of P-glycoprotein in the BBB has been suggested as one probable cause of drug resistance in epilepsy.

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.


'/>"/>

Contact: Robin Mackar
rmackar@niehs.nih.gov
919-541-0073
NIH/National Institute of Environmental Health Sciences
Source:Eurekalert

Related biology news :

1. Invasion of the brain tumors
2. HIV is a double hit to the brain
3. AIDS interferes with stem cells in the brain
4. 60 second test could help early diagnosis of common brain diseases
5. U of MN researchers discover noninvasive diagnostic tool for brain diseases
6. U of Minnesota researchers discover noninvasive diagnostic tool for brain diseases
7. Influence of sex and handedness on brain is similar in capuchin monkeys and humans
8. Inside the brain of a crayfish
9. Specific brain protein required for nerve cell connections to form and function
10. Brains timing linked with timescales of the natural visual world
11. Adult brain can change, study confirms
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/12/2016)... May 12, 2016 WearablesResearch.com , a ... the overview results from the Q1 wave of its ... wave was consumers, receptivity to a program where they ... a health insurance company. "We were surprised ... says Michael LaColla , CEO of Troubadour Research, ...
(Date:4/26/2016)... BANGALORE, India and LONDON ... Infosys Finacle, part of EdgeVerve Systems, a ... ), and Onegini today announced a partnership to ... banking solutions.      (Logo: http://photos.prnewswire.com/prnh/20151104/283829LOGO ... banks to provide their customers enhanced security to ...
(Date:4/14/2016)... 14, 2016 BioCatch ™, ... today announced the appointment of Eyal Goldwerger ... Goldwerger,s leadership appointment comes at a time ... the deployment of its platform at several of the ... which discerns unique cognitive and physiological factors, is a ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... YORK , June 23, 2016 ... trading session at 4,833.32, down 0.22%; the Dow Jones Industrial ... S&P 500 closed at 2,085.45, down 0.17%. Stock-Callers.com has initiated ... INFI ), Nektar Therapeutics (NASDAQ: NKTR ), ... Therapeutics Inc. (NASDAQ: BIND ). Learn more about ...
(Date:6/23/2016)... ... June 23, 2016 , ... Regulatory Compliance Associates® Inc. ... a free webinar on Performing Quality Investigations: Getting to Root Cause. ... at no charge. , Incomplete investigations are still a major concern to the ...
(Date:6/23/2016)... FRANCISCO , June 22, 2016  Amgen (NASDAQ: ... sponsorship of the QB3@953 life sciences incubator ... human health. The shared laboratory space at QB3@953 was ... overcome a key obstacle for many early stage organizations ... part of the sponsorship, Amgen launched two "Amgen Golden ...
(Date:6/22/2016)... SAN DIEGO , June 22, 2016 /PRNewswire/ ... partnership that will allow them to produce up ... (HiPSC) from one lot within one week. These ... their time laboriously preparing cells and spend more ... made possible through a proprietary, high-volume manufacturing process ...
Breaking Biology Technology: