Navigation Links
Blocking toxic effects could make clot-buster safer

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
Emory University

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. Identifies Toxic Combination
11. Amira Announces the Successful Completion of GLP Toxicity Studies for a Novel DP2 Antagonist.
Post Your Comments:
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a leading Health and Nutrition ... the Purzorb™process to full spectrum CBD oil will revolutionize the rapidly growing CBD market ... can be easily incorporated into liquid products, while reducing costs to end users. , ...
(Date:10/13/2017)... ... October 13, 2017 , ... Apple Rehab Shelton Lakes , which specializes ... of the facility as part of a disaster drill on October 3rd. , Apple ... Shelton City Emergency Manager, as well as the Connecticut Long Term Care Mutual ...
(Date:10/13/2017)... ... ... Ellevate Network, the leading network for professional women, brought together some of ... their inaugural Summit in New York City in June. The event was livestreamed with ... 3 million. To watch the Mobilize Women video, click here . , ...
(Date:10/13/2017)... ... October 13, 2017 , ... Talented ... the lowdown on sciatica in a new episode of "Success Files," which is ... events and innovation and investigates each subject in-depth with passion and integrity. , ...
(Date:10/13/2017)... ... 2017 , ... “America On The Brink”: the Christian history of the United ... the creation of published author, William Nowers. Captain Nowers and his wife, Millie, ... spent thirty years in the Navy. Following his career as a naval aviator ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... PARK, Calif. , Oct. 11, 2017  BioPharmX ... national scientific team that developed an innovative way to ... quantity of the delivery of new drugs. ... 2017 Fall Clinical Dermatology Conference will show how researchers ... General Hospital, Harvard Medical School used a suite of ...
(Date:10/10/2017)... 10, 2017  NDS received FDA 510(k) clearance in May 2017 ... display stand specifically designed for endoscopy environments. An innovative secondary monitor ... clinical solution to support the improvement of patient outcomes, procedural efficiency, ... ... ...
(Date:10/4/2017)... Korea , Oct. 4, 2017  South Korean-based ... next-generation CPR training aide "cprCUBE" on Kickstarter. The device ... compression during cardiac arrests with better efficiency compared to ... also offers real-time feedback on efficacy of the compression ... crowdfunding campaign has a goal to raise $5,000. ...
Breaking Medicine Technology: