(Press-News.org) Philadelphia, PA, October 16, 2014 – Traumatic spinal cord injury (SCI) is a devastating condition with few treatment options. Studies show that damage to the barrier separating blood from the spinal cord can contribute to the neurologic deficits that arise secondary to the initial trauma. Through a series of sophisticated experiments, researchers reporting in The American Journal of Pathology suggest that matrix metalloproteinase-3 (MMP-3) plays a pivotal role in disruption of the brain/spinal cord barrier (BSCB), cell death, and functional deficits after SCI. This link also presents new therapeutic possibilities.
"Matrix metalloproteinases (MMPs) are enzymes known to degrade the extracellular matrix and other extracellular proteins and are essential for remodeling of the extracellular matrix and wound healing. Excessive proteolytic activity of MMPs can be detrimental, leading to numerous pathological conditions, including blood brain barrier (BBB)/BSCB disruption after injury," explains Tae Young Yune, PhD, of the Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Korea. Although other MMPs have been linked to SCI (i.e. MMP-2, MMP-9, and MMP-12), there has been no previous direct evidence of a similar role for MMP-3.
By comparing mice that underwent spinal cord injury to a control group, investigators found that both MMP3 messenger RNA (mRNA) and MMP-3 protein levels in spinal cord segments were increased after SCI, peaking one day after surgery in the experimental group, whereas no changes were seen in the controls. MMP-3 immunoreactivity was detected in cells within the lesion site, invading neutrophils, and blood vessel endothelial cells in the area outside of the initial injured area (the penumbra).
Another series of experiments focused on the role of MMP-3 in BSCB permeability, using dye to visualize leakage through the BSCB. Similar to MMP-3 mRNA and protein levels, dye leakage reached a maximum one day after SCI. Leakage was lower in Mmp3 knockout mice that were genetically altered to be deficient in MMP-3 as well as in mice injected with either Mmp3 small interfering RNA (siRNA) or a general MMP inhibitor. Injection of MMP-3 into normal spinal cord also significantly increased dye leakage.
MMP-3 was found to contribute to the degradation of tight junction proteins that are responsible for maintaining the integrity of the BSCB barrier. In addition, the researchers reported that MMP-3 induced blood cell infiltration and hemorrhage after SCI in wild-type mice, but not in Mmp3 knockout mice. MMP-3 also mediated activation of other MMPs (MMP-2 and MMP-9) that are up-regulated after SCI. "This is the first study to demonstrate that MMP-3 is involved in MMP-9 activation in central nervous system injury," says Dr. Yune.
A significant finding was that mice deficient in MMP-3 showed significantly better functional recovery 14 and 28 days after injury than non-deficient mice. Histological analysis showed that after SCI the mice deficient in MMP-3 had smaller volumes of injured tissue and more healthy axons than non-deficient wild-type mice.
"The evidence suggests that BBB/BSCB disruption plays a pivotal role in acute and chronic neurological disorders. The inhibition of MMP-3 may be a promising therapeutic target for human central nervous system disease, including SCI," notes Dr. Yune.
INFORMATION: END
Presence of enzyme may worsen effects of spinal cord injury and impair long-term recovery
Findings suggest MMP-3 disrupts blood-spinal cord barrier and promotes hemorrhage, according to study published in The American Journal of Pathology
2014-10-17
ELSE PRESS RELEASES FROM THIS DATE:
Scientists opens black box on bacterial growth in cystic fibrosis lung infection
2014-10-17
Researchers from the University of Copenhagen have shown for the first time how bacteria can grow directly in the lungs of Cystic fibrosis patients, giving them the opportunity to get tremendous insights into bacteria behavior and growth in chronic infections.
The study also discovered the bacterial growth in chronic lung infections among cystic fibrosis (CF) patients was halted or slowed down by the immune cells. The researchers discovered the immune cells consumed all the oxygen and helped "suffocate" the bacteria, forcing the bacteria to switch to a much slower growth.
The ...
High-speed evolution in the lab
2014-10-17
DNA analysis has become increasingly efficient and cost-effective since the human genome was first fully sequenced in the year 2001. Sequencing a complete genome, however, still costs around US$1,000. Sequencing the genetic code of hundreds of individuals would therefore be very expensive and time-consuming. In particular for non-human studies, researchers very quickly hit the limit of financial feasibility.
Sequencing Groups Instead of Individuals
The solution to this problem is pool sequencing (Pool-Seq). Schlötterer and his team sequence entire groups of fruit ...
Scientific breakthrough will help design the antibiotics of the future
2014-10-17
Scientists have used computer simulations to show how bacteria are able to destroy antibiotics – a breakthrough which will help develop drugs which can effectively tackle infections in the future.
Researchers at the University of Bristol focused on the role of enzymes in the bacteria, which split the structure of the antibiotic and stop it working, making the bacteria resistant.
The new findings, published in Chemical Communications, show that it's possible to test how enzymes react to certain antibiotics.
It's hoped this insight will help scientists to develop ...
Physicists warning to 'nail beauty fans' applies to animals too
2014-10-17
The daily trimming of fingernails and toenails to make them more aesthetically pleasing could be detrimental and potentially lead to serious nail conditions. The research, carried out by experts in the School of Veterinary Medicine and Science at The University of Nottingham, will also improve our understanding of disease in the hooves of farm animals and horses.
Dr Cyril Rauch, a physicist and applied mathematician, together with his PhD Student Mohammed Cherkaoui-Rbati, devised equations to identify the physical laws that govern nail growth, and used them to throw ...
Emergency aid for overdoses
2014-10-17
This news release is available in German. To date, antidotes exist for only a very few drugs. When treating overdoses, doctors are often limited to supportive therapy such as induced vomiting. Treatment is especially difficult if there is a combination of drugs involved. So what can be done if a child is playing and accidentally swallows his grandmother's pills? ETH professor Jean-Christophe Leroux from the Institute of Pharmaceutical Sciences at ETH Zurich wanted to find an answer to this question. "The task was to develop an agent that could eliminate many different ...
How the brain leads us to believe we have sharp vision
2014-10-17
Its central finding is that our nervous system uses past visual experiences to predict how blurred objects would look in sharp detail.
"In our study we are dealing with the question of why we believe that we see the world uniformly detailed," says Dr. Arvid Herwig from the Neuro-Cognitive Psychology research group of the Faculty of Psychology and Sports Science. The group is also affiliated to the Cluster of Excellence Cognitive Interaction Technology (CITEC) of Bielefeld University and is led by Professor Dr. Werner X. Schneider.
Only the fovea, the central area of ...
UCLA research could help improve bladder function among people with spinal cord injuries
2014-10-17
People who have suffered spinal cord injuries are often susceptible to bladder infections, and those infections can cause kidney damage and even death.
New UCLA research may go a long way toward solving the problem. A team of scientists studied 10 paralyzed rats that were trained daily for six weeks with epidural stimulation of the spinal cord and five rats that were untrained and did not receive the stimulation. They found that training and epidural stimulation enabled the rats to empty their bladders more fully and in a timelier manner.
The study was published in ...
First step: From human cells to tissue-engineered esophagus
2014-10-17
In a first step toward future human therapies, researchers at The Saban Research Institute of Children's Hospital Los Angeles have shown that esophageal tissue can be grown in vivo from both human and mouse cells. The study has been published online in the journal Tissue Engineering, Part A.
The tissue-engineered esophagus formed on a relatively simple biodegradable scaffold after the researchers transplanted mouse and human organ-specific stem/progenitor cells into a murine model, according to principal investigator Tracy C. Grikscheit, MD, of the Developmental Biology ...
High-fat meals could be more harmful to males than females, according to new obesity research
2014-10-17
LOS ANGELES (Oct. 16, 2014) – Male and female brains are not equal when it comes to the biological response to a high-fat diet. Cedars-Sinai Diabetes and Obesity Research Institute scientist Deborah Clegg, PhD, and a team of international investigators found that the brains of male laboratory mice exposed to the same high-fat diet as their female counterparts developed brain inflammation and heart disease that were not seen in the females.
"For the first time, we have identified remarkable differences in the sexes when it comes to how the body responds to high-fat ...
Divide and conquer: Novel trick helps rare pathogen infect healthy people
2014-10-17
New research into a rare pathogen has shown how a unique evolutionary trait allows it to infect even the healthiest of hosts through a smart solution to the body's immune response against it.
Scientists at the University of Birmingham have explained how a particular strain of a fungus, Cryptococcus gattii, responds to the human immune response and triggers a 'division of labour' in its invading cells, which can lead to life-threatening infections.
Once inhaled, the pathogen can spread through the body to cause pneumonia or meningitis. The outbreak strain of this fungus ...
LAST 30 PRESS RELEASES:
Clinical trial at Emory University reveals twice-yearly injection to be 96% effective in HIV prevention
Discovering the traits of extinct birds
Are health care disparities tied to worse outcomes for kids with MS?
For those with CTE, family history of mental illness tied to aggression in middle age
The sound of traffic increases stress and anxiety
Global food yields have grown steadily during last six decades
Children who grow up with pets or on farms may develop allergies at lower rates because their gut microbiome develops with more anaerobic commensals, per fecal analysis in small cohort study
North American Early Paleoindians almost 13,000 years ago used the bones of canids, felids, and hares to create needles in modern-day Wyoming, potentially to make the tailored fur garments which enabl
Higher levels of democracy and lower levels of corruption are associated with more doctors, independent of healthcare spending, per cross-sectional study of 134 countries
In major materials breakthrough, UVA team solves a nearly 200-year-old challenge in polymers
Wyoming research shows early North Americans made needles from fur-bearers
Preclinical tests show mRNA-based treatments effective for blinding condition
Velcro DNA helps build nanorobotic Meccano
Oceans emit sulfur and cool the climate more than previously thought
Nanorobot hand made of DNA grabs viruses for diagnostics and blocks cell entry
Rare, mysterious brain malformations in children linked to protein misfolding, study finds
Newly designed nanomaterial shows promise as antimicrobial agent
Scientists glue two proteins together, driving cancer cells to self-destruct
Intervention improves the healthcare response to domestic violence in low- and middle-income countries
State-wide center for quantum science: Karlsruhe Institute of Technology joins IQST as a new partner
Cellular traffic congestion in chronic diseases suggests new therapeutic targets
Cervical cancer mortality among US women younger than age 25
Fossil dung reveals clues to dinosaur success story
New research points way to more reliable brain studies
‘Alzheimer’s in dish’ model shows promise for accelerating drug discovery
Ultraprocessed food intake and psoriasis
Race and ethnicity, gender, and promotion of physicians in academic medicine
Testing and masking policies and hospital-onset respiratory viral infections
A matter of life and death
Huge cost savings from more efficient use of CDK4/6 inhibitors in metastatic breast cancer reported in SONIA study
[Press-News.org] Presence of enzyme may worsen effects of spinal cord injury and impair long-term recoveryFindings suggest MMP-3 disrupts blood-spinal cord barrier and promotes hemorrhage, according to study published in The American Journal of Pathology