Many safe therapy forms, however, are often associated with hazards, and therefore indications for therapy must be weighed on an individual basis. In stroke thrombolysis, it is the risk of perithrombolytic hemorrhage formation and expansive brain edema that are most feared complications, and may preclude from administering the therapy. Even after proper precautions, perithrombolytic hemorrhages occur in 6 to 10 % of treated patients. Therefore, experimental research is needed to clarify the mechanisms leading to these complications.
The now reported study led by Dr. Perttu J. Lindsberg from the Helsinki University Central Hospital investigated thrombolytics-related brain hemorrhage formation in an experimental stroke model in rats. It found that, in addition to the clot lysing effect, the drug used for this purpose, alteplase (recombinant tissue plasminogen activator) also possesses proinflammatory properties and activates and degranulates mast cells, a kind of tissue-based immune cell. On degranulation, mast cells release potent enzymes that cleave proteins (eg, chymase, tryptase, and metalloproteases) in the vessel wall. The result is increased vascular permeability, which can lead to hazardous brain edema and potentially to frank brain hemorrhage formation. A pharmacological mast cell stabilizer, cromoglycate, was administered before alteplase, and it reduced these detrimental effects significantly and led to improved neurological outcome and reduced mortality.
The amount of brain hemorrhage was reduced by 97% at 3 hours, by 76% at 6 hours, and by 96% after 24 hours of follow-up. Ischemic brain edema was reduced by 80% at 3 hours, by 55% at 6 hours and by 85% after 24 hours of follow-up. The mortality in control group was 29%, 64% in alteplase group, and 0% in a group treated with a combination of alteplase and cromoglycate. kromoglikaatti+alteplaasiryhmässä 0%). Furthermore, genetically engineered animals were used which lacked mast cells, and they showed minimal brain edema and alteplase-related hemorrhage formation. They also had improved neurological outcome and mortality compared with wild-type littermates. In addition to proteolytic enzymes, mast cells release vasodilators such as histamine as well as heparin (s.c. “blood thinning” anticoagulant drug), which may locally prevent blood coagulation, predispose to bleeding and edema formation and ultimately lead to hazardous expansion of hemorrhagic and edematous brain events. The intracranial space is tight and does not allow expansion of its tissue content without harmful and potentially fatal consequences.
This study revealed a novel proinflammatory cellular mechanism related to an every-day dilemma in routine patient care that may provide a novel pharmacological target if confirmed in the clinical setting. At best, mast cell stabilization could eventually be applied as an adjuvant to thrombolysis.
Terttu Nurro | alfa
Cholesterol-lowering drugs may fight infectious disease
22.08.2017 | Duke University
Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy