Navigation Links
Brain study may lead to improved epilepsy treatments

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
NIH/National Institute of Environmental Health Sciences

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:
(Date:11/9/2015)... SAN JOSE, Calif. , Nov. 9, 2015 /PRNewswire/ ... of human interface solutions, today announced broader entry into ... of vehicle-specific solutions that match the pace of consumer ... drivers, and biometric sensors are ideal for the automotive ... the vehicle. Europe , ...
(Date:10/29/2015)... Oct. 29, 2015   MedNet Solutions , an ... spectrum of clinical research, is pleased to announce that ... Association (MHTA) as one of only three finalists for ... – Small and Growing" category. The Tekne Awards honor ... shown superior technology innovation and leadership. ...
(Date:10/29/2015)... ARBOR, Mich. , Oct. 29, 2015 /PRNewswire/ ... Eurofins Genomics for U.S. distribution of its DNA ... DNA-seq kit and Rubicon,s new ThruPLEX Plasma-seq kit. ... to enable the preparation of NGS libraries for ... plasma for diagnostic and prognostic applications in cancer ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... Nov. 24, 2015  Clintrax Global, Inc., a worldwide provider of ... , today announced that the company has set a new quarterly ... quarter on quarter growth posted for Q3 of 2014 to Q3 ... Mexico , with the establishment of an ... --> United Kingdom and ...
(Date:11/24/2015)... ... , ... This fall, global software solutions leader SAP and AdVenture Capital brought ... pitch their BIG ideas to improve health and wellness in their schools. , Now, ... the title of SAP's Teen Innovator, an all-expenses paid trip to Super Bowl 50, ...
(Date:11/24/2015)... LEXINGTON, Massachusetts , November 24, 2015 ... Officer, will participate in the Piper Jaffray 27 th Annual ... on Tuesday, December 1, 2015, at 8:30 a.m. EST (1:30 p.m. ... Poulton , Chief Financial Officer, will participate in the Piper Jaffray ... City , NY on Tuesday, December 1, 2015, at 8:30 ...
(Date:11/24/2015)... 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) today announced that its ... at 11:00 a.m. Israel time, at the law ... Allon Street, 36 th Floor, Tel Aviv, Israel ... and Izhak Tamir to the Board of Directors; ... directors; , approval of an amendment to certain terms of options ...
Breaking Biology Technology: