Navigation Links
Blocking toxic effects could make clot-buster safer
Date:1/23/2009

ATLANTA--Since the introduction of the life-saving clot-busting drug tPA more than a decade ago, evidence has been accumulating that tPA (tissue-type plasminogen activator) can be a double-edged sword for a brain affected by stroke. Although it remains the only FDA-approved treatment for acute stroke, tPA can also contribute to inflammation and brain cell damage.

Scientists at Emory University School of Medicine are testing strategies for blocking LRP1, a molecule that appears to transmit inflammation signals triggered by tPA. They have found that in mice, genetically removing LRP1 from certain brain cells called microglia softens tPA's impact on the brain.

The results, published online this week by the American Journal of Pathology, suggest that blocking tPA's toxic effects could make it safer and allow doctors to use it more often on patients experiencing a stroke.

"tPA is a protein released naturally by the body in response to a blood clot," says Manuel Yepes, MD, PhD, assistant professor of neurology at Emory University School of Medicine. "But it's clearly not just lysing the clot."

Doctors in community hospitals can often be reluctant to administer tPA to patients who appear to be having a stroke, Yepes says. One reason is that tPA has been shown to increase the risk of bleeding in the brain, he says.

Researchers have shown that tPA treatment increases the permeability of the blood-brain barrier, and that it can cross from the blood vessels into the brain tissue, generating inflammation. tPA targets cells called microglia, which are similar to white blood cells of the immune system, although they live in the brain.

"Our strategy was to show that by blocking LRP1, you can prevent the inflammatory response to tPA," Yepes says. "This can be done either genetically, by deleting LRP1, or perhaps pharmacologically."

Yepes and his colleagues are now testing a natural inhibitor of LRP1 called RAP in the laboratory. Co-treating or even pre-treating stroke patients with RAP might soften tPA's effects.

Researchers had previously been unable to examine the effects of deleting LRP1, a protein involved in transporting cholesterol and other molecules around the brain, because mice completely lacking the gene die in the womb.

Yepes and his colleagues collaborated with Dudley Strickland, PhD, professor of surgery and physiology at University of Maryland School of Medicine, who provided mice deficient in LRP1 in macrophages (white blood cells) and microglia only.

The authors showed that the genetically altered mice have half the number of activated microglia in the brain after treatment with tPA. In addition, the volume of brain tissue damaged by a simulated stroke was cut in half in the genetically altered mice.


'/>"/>

Contact: Jennifer Johnson
jrjohn9@emory.edu
404-727-5696
Emory University
Source:Eurekalert

Related medicine news :

1. Stopping ovarian cancer by blocking proteins coded by notorious gene
2. Blocking Oncogene Can Stop Spread of Ovarian Cancer
3. Blocking molecular pathway with whimsical name possible therapeutic target for pancreatic cancer
4. Pennsylvania Medical Society and AARP Criticize Senator Specter for Blocking Bill to Protect Access to Doctors and Improve Medicare
5. Blocking signaling protein prevents prostate cancer spread, Jefferson scientists find
6. Blocking the effect of inflammation-causing cells lowered prostate cancer cells invasion
7. Blocking protein kills prostate cancer cells, inhibits tumor growth, Jefferson scientists find
8. Blocking Potent Oxidant Could Prevent Morphine Tolerance
9. Pre-emptive treatment helped curtail skin toxicity with panitumumab
10. DrScore.com Identifies Toxic Combination
11. Amira Announces the Successful Completion of GLP Toxicity Studies for a Novel DP2 Antagonist.
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/27/2016)... ... 27, 2016 , ... An educational campaign aimed at everyone ... courtesy of awareness-driven celebrities and thought leaders. It also provides insight to the ... leaders such as Bioness. , As patients feel increasingly concerned about the ...
(Date:5/27/2016)... Killeen, Texas (PRWEB) , ... May 27, 2016 , ... ... with satisfying Army body fat composition regulations. This is the first time that ... are normally screened at least every six months to ensure they meet the prescribed ...
(Date:5/27/2016)... ... May 27, 2016 , ... Aimed at nurses and employees in the health ... of leaders in the nursing and health care industry. It also provides insight to ... Christian University. , As the nursing industry is coming out of one of ...
(Date:5/27/2016)... ... 27, 2016 , ... With a team of certified experts, ... Aside from its GMP accreditation, Validation Center is also a registered authority of ... and staff. , Validation Center is ISO17025 accredited and only offers its clients ...
(Date:5/26/2016)... ... 26, 2016 , ... There are many ways to cook a hot dog, ... that Americans prefer their dogs straight off the grill. Of the 90 percent of ... way to cook a hot dog, far outpacing other cooking methods such as steaming ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... Germany and GERMANTOWN, Maryland ... (NASDAQ: QGEN ; Frankfurt Prime Standard: QIA) today ... co-development agreement with Therawis Diagnostics GmbH to develop and commercialize ... develop and market PITX2 as a marker to predict effectiveness ... cancer patients. "We are pleased to partner with ...
(Date:5/25/2016)... , May 25, 2016 ... & Expo earlier this month, the numbers and momentum ... continue to climb into the billions, more research and ... released 4th Edition State of Legal Marijuana Markets Report ... cannabis-focused data-analysis firm, much of the increase in sector ...
(Date:5/25/2016)... , May 25, 2016 ... employing the precision of circulating tumour DNA (ctDNA) ... announces the appointment of Professor Clive Morris ... medical leadership across the clinical development programme, scientific ... products help deliver significant improvements in clinical outcomes ...
Breaking Medicine Technology: