Posts tagged brain damage
Articles and news from the latest research reports.
Alzheimer’s patients show striking individual differences in molecular basis of disease
Alzheimer’s disease is thought to be caused by the buildup of abnormal, thread-like protein deposits in the brain, but little is known about the molecular structures of these so-called beta-amyloid fibrils. A study published by Cell Press September 12th in the journal Cell has revealed that distinct molecular structures of beta-amyloid fibrils may predominate in the brains of Alzheimer’s patients with different clinical histories and degrees of brain damage. The findings pave the way for new patient-specific strategies to improve diagnosis and treatment of this common and debilitating disease.
"This work represents the first detailed characterization of the molecular structures of beta-amyloid fibrils that develop in the brains of patients with Alzheimer’s disease," says senior study author Robert Tycko of the National Institutes of Health. "This detailed structural model may be used to guide the development of chemical compounds that bind to these fibrils with high specificity for purposes of diagnostic imaging, as well as compounds that inhibit fibril formation for purposes of prevention or therapy."
Tycko and his team had previously noticed that beta-amyloid fibrils grown in a dish have different molecular structures, depending on the specific growth conditions. Based on this observation, they suspected that fibrils found in the brains of patients with Alzheimer’s disease are also variable and that these structural variations might relate to each patient’s clinical history. But it has not been possible to directly study the structures of fibrils found in patients because of their low abundance in the brain.
To overcome this hurdle, Tycko and his collaborators developed a new experimental protocol. They extracted beta-amyloid fibril fragments from the brain tissue of two patients with different clinical histories and degrees of brain damage and then used these fragments to grow a large quantity of fibrils in a dish. They found that a single fibril structure prevailed in the brain tissue of each patient, but the molecular structures were different between the two patients.
"This may mean that fibrils in a given patient appear first at a single site in the brain, then spread to other locations while retaining the identical molecular structure," Tycko says. "Our study also shows that certain fibril structures may be more likely than others to cause Alzheimer’s disease, highlighting the importance of developing imaging agents that target specific fibril structures to improve the reliability and specificity of diagnosis."
(Source: eurekalert.org)
Questions answered with the pupils of your eyes
Patients who are otherwise completely unable to communicate can answer yes or no questions within seconds with the help of a simple system—consisting of just a laptop and camera—that measures nothing but the size of their pupils. The tool, described and demonstrated in Current Biology, a Cell Press publication, on August 5 takes advantage of changes in pupil size that naturally occur when people do mental arithmetic. It requires no specialized equipment or training at all.
The new pupil response system might not only help those who are severely motor-impaired communicate, but might also be extended to assessing the mental state of patients whose state of consciousness is unclear, the researchers say.
"It is remarkable that a physiological system as simple as the pupil has such a rich repertoire of responses that it can be used for a task as complex as communication," says Wolfgang Einhäuser of Philipps-Universität Marburg in Germany.
The researchers asked healthy people to solve a math problem only when the correct answer to a yes or no question was shown to them on a screen. The mental load associated with solving that problem caused an automatic increase in pupil size, which the researchers showed they could measure and translate into an accurate answer to questions like “Are you 20 years old?”
They then tested out their pupil response algorithm on seven “typical” locked-in patients who had suffered brain damage following a stroke. In many cases, they were able to discern an answer based on pupil size alone.
"We find it remarkable that the system worked almost perfectly in all healthy observers and then could be transferred directly from them to the patients, with no need for training or parameter adjustment," Einhäuser says.
While the system could still use improvement in terms of speed and accuracy, those are technical hurdles Einhäuser is confident they can readily overcome. Their measures of pupil response could already make an important difference for those who need it most.
"For patients with altered state of consciousness—those who are in a coma or other unresponsive state—any communication is a big step forward," he says.
New Scientific Analysis Shines a Light on Ötzi the Iceman’s Dark Secrets
Protein investigation supports brain injury theory and opens up new research possibilities for mummies
After decoding the Iceman’s genetic make-up, a research team from the European Academy of Bolzano/Bozen (EURAC), Saarland University, Kiel University and other partners has now made another major breakthrough in mummy research: using just a pinhead-sized sample of brain tissue from the world-famous glacier corpse, the team was able to extract and analyse proteins to further support the theory that Ötzi suffered some form of brain damage in the final moments of his life.
Two dark coloured areas at the back of the Iceman’s cerebrum had first been mentioned back in 2007 during a discussion about the fracture to his skull. Scientists surmised from a CAT scan of his brain that he had received a blow to the forehead during his deadly attack that caused his brain to knock against the back of his head, creating dark spots from the bruising. Till now, this hypothesis had been left unexplored.
In 2010, with the help of computer-controlled endoscopy, two samples of brain tissue the size of a pinhead were extracted from the glacier mummy. This procedure was carried out via two tiny (previously existing) access holes and was thus minimally invasive. Microbiologist Frank Maixner (EURAC, Institute for Mummies and the Iceman) and his fellow scientist Andreas Tholey (Institute for Experimental Medicine, Kiel University) conducted two parallel, independent studies on the tiny bundles of cells. Tholey’s team provided the latest technology used in the study of complex protein mixtures known as “proteomes”. The various analyses were coordinated by Frank Maixner and Andreas Keller.
The protein research revealed a surprising amount of information. Scientists were able to identify numerous brain proteins, as well as proteins from blood cells. Microscopic investigation also confirmed the presence of astonishingly well-preserved neural cell structures and clotted blood cells. On the one hand, this led the scientists to conclude that the recovered samples did indeed come from brain tissue in remarkably good condition (the proteins contained amino acid sequence features specific to Ötzi). On the other hand, these blood clots in a corpse almost devoid of blood provided further evidence that Ötzi’s brain had possibly suffered bruising shortly before his death. Whether this was due to a blow to the forehead or a fall after being injured by the arrow remains unclear.
The discoveries represent a major breakthrough for the scientists. The research team emphasised that “the use of new protein-analysis methods has enabled us to pioneer this type of protein investigation on the soft tissue of a mummified human, extracting from the tiniest sample a vast quantity of data which in the future may well answer many further questions.” While many DNA samples from mummies are difficult or impossible to analyse because of natural biological decay, one can often still find proteins in tissue samples which allow a closer analysis and provide valuable information, explained Andreas Tholey: “Proteins are the decisive players in tissues and cells, and they conduct most of the processes which take place in cells. Identification of the proteins is therefore key to understanding the functional potential of a particular tissue. DNA is always constant, regardless of from where it originates in the body, whereas proteins provide precise information about what is happening in specific regions within the body.” Protein analysis of mummified tissue makes an especially valuable contribution to DNA research, Maixner added: “Investigating mummified tissue can be very frustrating. The samples are often damaged or contaminated and do not necessarily yield results, even after several attempts and using a variety of investigative methods. When you think that we have succeeded in identifying actual tissue changes in a human who lived over 5,000 years ago, you can begin to understand how pleased we are as scientists that we persisted with our research after many unsuccessful attempts. It has definitely proved worthwhile!”
The results of this joint study are published in the renowned journal “Cellular and Molecular Life Sciences”. Along with a sample taken from the Iceman´s stomach content, more than a dozen tissue samples from less well preserved mummies from all over the world will be submitted to this new protein-based research method and should provide insights which previously had not been possible.
Low Doses of THC Can Halt Brain Damage
Extremely low doses of marijuana’s psychoactive component protect brain before and after injury, says TAU researcher
Though marijuana is a well-known recreational drug, extensive scientific research has been conducted on the therapeutic properties of marijuana in the last decade. Medical cannabis is often used by sufferers of chronic ailments, including cancer and post-traumatic stress disorder, to combat pain, insomnia, lack of appetite, and other symptoms.
Now Prof. Yosef Sarne of Tel Aviv University’s Adelson Center for the Biology of Addictive Diseases at the Sackler Faculty of Medicine says that the drug has neuroprotective qualities as well. He has found that extremely low doses of THC — the psychoactive component of marijuana — protects the brain from long-term cognitive damage in the wake of injury from hypoxia (lack of oxygen), seizures, or toxic drugs. Brain damage can have consequences ranging from mild cognitive deficits to severe neurological damage.
Previous studies focused on injecting high doses of THC within a very short time frame — approximately 30 minutes — before or after injury. Prof. Sarne’s current research, published in the journals Behavioural Brain Research and Experimental Brain Research, demonstrates that even extremely low doses of THC — around 1,000 to 10,000 times less than that in a conventional marijuana cigarette — administered over a wide window of 1 to 7 days before or 1 to 3 days after injury can jumpstart biochemical processes which protect brain cells and preserve cognitive function over time.
This treatment, especially in light of the long time frame for administration and the low dosage, could be applicable to many cases of brain injury and be safer over time, Prof. Sarne says.
Conditioning the brain
While performing experiments on the biology of cannabis, Prof. Sarne and his fellow researchers discovered that low doses of the drug had a big impact on cell signalling, preventing cell death and promoting growth factors. This finding led to a series of experiments designed to test the neuroprotective ability of THC in response to various brain injuries.
In the lab, the researchers injected mice with a single low dose of THC either before or after exposing them to brain trauma. A control group of mice sustained brain injury but did not receive the THC treatment. When the mice were examined 3 to 7 weeks after initial injury, recipients of the THC treatment performed better in behavioral tests measuring learning and memory. Additionally, biochemical studies showed heightened amounts of neuroprotective chemicals in the treatment group compared to the control group.
The use of THC can prevent long-term cognitive damage that results from brain injury, the researchers conclude. One explanation for this effect is pre- and post-conditioning, whereby the drug causes minute damage to the brain to build resistance and trigger protective measures in the face of much more severe injury, explains Prof. Sarne. The low dosage of THC is crucial to initiating this process without causing too much initial damage.
Preventative and long-term use
According to Prof. Sarne, there are several practical benefits to this treatment plan. Due to the long therapeutic time window, this treatment can be used not only to treat injury after the fact, but also to prevent injury that might occur in the future. For example, cardiopulmonary heart-lung machines used in open heart surgery carry the risk of interrupting the blood supply to the brain, and the drug can be delivered beforehand as a preventive measure. In addition, the low dosage makes it safe for regular use in patients at constant risk of brain injury, such as epileptics or people at a high risk of heart attack.
Prof. Sarne is now working in collaboration with Prof. Edith Hochhauser of the Rabin Medical Center to test the ability of low doses of THC to prevent damage to the heart. Preliminary results indicate that they will find the same protective phenomenon in relation to cardiac ischemia, in which the heart muscle receives insufficient blood flow.
(Source: aftau.org)
Brain rewires itself after damage or injury
When the brain’s primary “learning center” is damaged, complex new neural circuits arise to compensate for the lost function, say life scientists from UCLA and Australia who have pinpointed the regions of the brain involved in creating those alternate pathways — often far from the damaged site.
The research, conducted by UCLA’s Michael Fanselow and Moriel Zelikowsky in collaboration with Bryce Vissel, a group leader of the neuroscience research program at Sydney’s Garvan Institute of Medical Research, appears this week in the early online edition of the journal Proceedings of the National Academy of Sciences.
The researchers found that parts of the prefrontal cortex take over when the hippocampus, the brain’s key center of learning and memory formation, is disabled. Their breakthrough discovery, the first demonstration of such neural-circuit plasticity, could potentially help scientists develop new treatments for Alzheimer’s disease, stroke and other conditions involving damage to the brain.
For the study, Fanselow and Zelikowsky conducted laboratory experiments with rats showing that the rodents were able to learn new tasks even after damage to the hippocampus. While the rats needed more training than they would have normally, they nonetheless learned from their experiences — a surprising finding.
"I expect that the brain probably has to be trained through experience," said Fanselow, a professor of psychology and member of the UCLA Brain Research Institute, who was the study’s senior author. "In this case, we gave animals a problem to solve."
After discovering the rats could, in fact, learn to solve problems, Zelikowsky, a graduate student in Fanselow’s laboratory, traveled to Australia, where she worked with Vissel to analyze the anatomy of the changes that had taken place in the rats’ brains. Their analysis identified significant functional changes in two specific regions of the prefrontal cortex.
"Interestingly, previous studies had shown that these prefrontal cortex regions also light up in the brains of Alzheimer’s patients, suggesting that similar compensatory circuits develop in people," Vissel said. "While it’s probable that the brains of Alzheimer’s sufferers are already compensating for damage, this discovery has significant potential for extending that compensation and improving the lives of many."
The hippocampus, a seahorse-shaped structure where memories are formed in the brain, plays critical roles in processing, storing and recalling information. The hippocampus is highly susceptible to damage through stroke or lack of oxygen and is critically inolved in Alzheimer’s disease, Fanselow said.
"Until now, we’ve been trying to figure out how to stimulate repair within the hippocampus," he said. "Now we can see other structures stepping in and whole new brain circuits coming into being."
Zelikowsky said she found it interesting that sub-regions in the prefrontal cortex compensated in different ways, with one sub-region — the infralimbic cortex — silencing its activity and another sub-region — the prelimbic cortex — increasing its activity.
"If we’re going to harness this kind of plasticity to help stroke victims or people with Alzheimer’s," she said, "we first have to understand exactly how to differentially enhance and silence function, either behaviorally or pharmacologically. It’s clearly important not to enhance all areas. The brain works by silencing and activating different populations of neurons. To form memories, you have to filter out what’s important and what’s not."
Complex behavior always involves multiple parts of the brain communicating with one another, with one region’s message affecting how another region will respond, Fanselow noted. These molecular changes produce our memories, feelings and actions.
"The brain is heavily interconnected — you can get from any neuron in the brain to any other neuron via about six synaptic connections," he said. "So there are many alternate pathways the brain can use, but it normally doesn’t use them unless it’s forced to. Once we understand how the brain makes these decisions, then we’re in a position to encourage pathways to take over when they need to, especially in the case of brain damage.
"Behavior creates molecular changes in the brain; if we know the molecular changes we want to bring about, then we can try to facilitate those changes to occur through behavior and drug therapy," he added. I think that’s the best alternative we have. Future treatments are not going to be all behavioral or all pharmacological, but a combination of both."
Wireless signals could transform brain trauma diagnostics
New technology developed at the University of California, Berkeley, is using wireless signals to provide real-time, non-invasive diagnoses of brain swelling or bleeding.
The device analyzes data from low energy electromagnetic waves that are similar to those used to transmit radio and mobile signals. The technology, described in the May 14 issue of the journal PLOS ONE, could potentially become a cost-effective tool for medical diagnostics and to triage injuries in areas where access to medical care, especially medical imaging, is limited.
The researchers tested a prototype in a small-scale pilot study of healthy adults and brain trauma patients admitted to a military hospital for the Mexican Army. The results from the healthy participants were clearly distinguishable from the patients with brain damage, and data for bleeding was distinct from data for swelling.
Boris Rubinsky, Professor of the Graduate School at UC Berkeley’s Department of Mechanical Engineering, led the research team along with César A. González, a professor in Mexico at the Instituto Politécnico Nacional, Escuela Superior de Medicina (National Polytechnic Institute’s Superior School of Medicine).
“There are large populations in Mexico and the world that do not have adequate access to advanced medical imaging, either because it is too costly or the facilities are far away,” said González. “This technology is inexpensive, it can be used in economically disadvantaged parts of the world and in rural areas that lack industrial infrastructure, and it may substantially reduce the cost and change the paradigm of medical diagnostics. We have also shown that the technology could be combined with cell phones for remote diagnostics.”
Rubinsky noted that symptoms of serious head injuries and brain damage are not always immediately obvious, and for treatment, time is of the essence. For example, the administration of clot-busting medication for certain types of strokes must be given within three hours of the onset of symptoms.
“Some people might delay traveling to a hospital to get examined because it is an hour or more away, or because it is exceedingly expensive,” said Rubinsky. “If people had access to an affordable device that could indicate whether there is brain damage or not, they could then make an informed decision about making that trip to a facility to get prompt treatment, which is especially important for head injuries.”
The researchers took advantage of the characteristic changes in tissue composition and structure in brain injuries. For brain edemas, swelling results from an increase in fluid in the tissue. For brain hematomas, internal bleeding causes the buildup of blood in certain regions of the brain. Because fluid conducts electricity differently than brain tissue, it is possible to measure changes in electromagnetic properties. Computer algorithms interpret the changes to determine the likelihood of injury.
The study involved 46 healthy adults, ages 18 to 48, and eight patients with brain damage, ages 27 to 70.
The engineers fashioned two coils into a helmet-like device that was fitted over the heads of the study participants. One coil acted as a radio emitter and the other served as the receiver. Electromagnetic signals were broadcast through the brain from the emitter to the receiver.
“We have adjusted the coils so that if the brain works perfectly, we have a clean signal,” said Rubinsky. “Whenever there are interferences in the functioning of the brain, we detect them as changes in the received signal. We can tell from the changes, or ‘noises,’ what the brain injury is.”
Rubinsky noted that the waves are extremely weak, and are comparable to standing in a room with the radio or television turned on.
The device’s diagnoses for the brain trauma patients in the study matched the results obtained from conventional computerized tomography (CT) scans.
The tests also revealed some insights into the aging brain.
“With an increase in age, the average electromagnetic transmission signature of a normal human brain changes and approaches that of younger patients with a severe medical condition of hematoma in the brain,” said González. “This suggests the potential for the device to be used as an indication for the health of the brain in older patients in a similar way in which measurements of blood pressure, ECG, cholesterol or other health markers are used for diagnostic of human health conditions.”
Imaging Technique Could Help Traumatic Brain Injury Patients
A new application of an existing medical imaging technology could help predict long-term damage in patients with traumatic brain injury, according to a recent UC San Francisco study.
The authors of the study analyzed brain scans using applied rapid automated resting state magnetoencephalography (MEG) imaging, a technique used to map brain activity by recording magnetic fields produced by natural electrical currents in the brain. They discovered “abnormally decreased functional connectivity” – or possible long-term brain damage – could persist years after a person suffers even a mild form of traumatic brain injury.
“We were hoping that areas of abnormal brain activity would match up with some of the functional measures such as patients’ symptoms after injury, and we saw such correlation,” said senior author Pratik Mukherjee, MD, PhD, associate professor in residence at the UCSF School of Medicine.
In a study published on April 19 in the Journal of Neurosurgery, UCSF researchers analyzed brain connectivity data on 14 male and seven female patients, whose median age was 29. Brain connectivity refers to a pattern of causal interactions between specific parts within a nervous system. Eleven patients had mild, one had moderate, and three had severe forms of traumatic brain injury. Six patients suffered no brain injury.
“Once we have connectivity information, we can create a template of what it looks like in a normal subject. When we have subjects that have had head injuries, we can compare their connectivity pattern to that of the normal subjects with an automated computer algorithm,” Mukherjee said. “And that will automatically detect areas of abnormally low and abnormally high connectivity compared to the normal database.”
MEG imaging provides much richer information than a typical magnetic resonance imaging (MRI), which uses magnetic field and radio wave energy to give a static image of the brain or other internal structures of the body.
“If you scan someone a couple months after the trauma with an MRI, and you scan them again a couple of years after the trauma, it’s going to look the same,” Mukherjee said. “With MEG, we can characterize simple systems in much more in fine grain detail. It produces the most detailed activity mapping of the brain.”
Although MEG signals were first measured in 1968, the technology has not been widely used for patients with traumatic brain injury until recently.
“It takes a minute or two to complete an MEG scan and it automatically detects the areas of abnormality using a computer algorithm,” Mukherjee said. “And it seems to be fairly sensitive because it’s showing us areas of abnormality even in people where MRIs missed some abnormalities.”
Every year approximately 1.7 million people in the United States suffer from traumatic brain injury, which costs the U.S. health care system an estimated $60 billion according to the U.S. Centers for Disease Control and Prevention. The most common forms of traumatic brain injury are suffered by athletes, members of the military, and those involved in motor vehicle collisions or occupational injuries.
“This is a preliminary study testing a new technique with a small sample, which makes it difficult to have enough statistical power to make such correlations,” Mukherjee said. “But I think this is an important step in our quest to help people suffering from traumatic brain injuries.”
Experts Call for Research on Prevalence of Delayed Neurological Dysfunction After Head Injury
One of the most controversial topics in neurology today is the prevalence of serious permanent brain damage after traumatic brain injury (TBI). Long-term studies and a search for genetic risk factors are required in order to predict an individual’s risk for serious permanent brain damage, according to a review article published by Sam Gandy, MD, PhD, from the Icahn School of Medicine at Mount Sinai in a special issue of Nature Reviews Neurology dedicated to TBI.
About one percent of the population in the developed world has experienced TBI, which can cause serious long-term complications such as Alzheimer’s disease (AD) or chronic traumatic encephalopathy (CTE), which is marked by neuropsychiatric features such as dementia, Parkinson’s disease, depression, and aggression. Patients may be normal for decades after the TBI event before they develop AD or CTE. Although first described in boxers in the 1920s, the association of CTE with battlefield exposure and sports, such as football and hockey, has only recently begun to attract public attention.
"Athletes such as David Duerson and Junior Seau have brought to light the need for preventive measures and early diagnosis of CTE, but it remains highly controversial because hard data are not available that enable prediction of the prevalence, incidence, and individual risk for CTE," said Dr. Gandy, who is Professor of Neurology and Psychiatry and Director of the Center for Cognitive Health at Mount Sinai. "We need much more in the way of hard facts before we can advise the public of the proper level of concern."
Led by Dr. Gandy, the authors evaluated the pathological impact of single-incident TBI, such as that sustained during military combat; and mild, repetitive TBI, as seen in boxers and National Football League (NFL) players to learn what measures need to be taken to identify risk and incidence early and reduce long-term complications.
Mild, repetitive TBI, as is seen in boxers, football players, and occasionally military veterans who suffer multiple blows to the head, is most often associated with CTE, or a condition called “boxer’s dementia.” Boxing scoring includes a record of knockouts, providing researchers with a starting point in interpreting an athlete’s risk. But no such records exist for NFL players or soldiers on the battlefield.
Dr. Gandy and the authors of the Nature Reviews Neurology piece suggest recruiting large cohorts of players and military veterans in multi-center trials, where players and soldiers maintain a TBI diary for the duration of their lives. The researchers also suggest a genome-wide association study to clearly identify risk factors of CTE. “Confirmed biomarkers of risk, diagnostic tools, and long-term trials are needed to fully characterize this disease and develop prevention and treatment strategies,” said Dr. Gandy.
Amyloid imaging, which has recently been approved by the U.S. Food and Drug Administration, may be useful as a monitoring tool in TBI, since amyloid plaques are a hallmark symptom of AD-type neurodegeneration. Amyloid imaging consists of a PET scan with an injection of a contrast agent called florbetapir, which binds to amyloid plaque in the brain, allowing researchers to visualize plaque deposits and determine whether the diagnosis is CTE or AD, and monitor progression over time. Tangle imaging is expected to be available soon, complementing amyloid imaging and providing an affirmative diagnosis of CTE. Dr. Gandy and colleagues recently reported the use of amyloid imaging to exclude AD in a retired NFL player with memory problems under their care at Mount Sinai.
Clinical diagnosis and evaluation of mild, repetitive TBI is a challenge, indicating a significant need for new biomarkers to identify damage, report the authors. Measuring cerebrospinal fluid (CSF) may reflect damage done to neurons post-TBI. Previous research has identified a marked increase in CSF biomarkers in boxers when the CSF is taken soon after a fight, and this may predict which boxers are more likely to develop detrimental long-term effects. CSF samples are now only obtained by invasive lumbar puncture; a blood test would be preferable.
"Biomarkers would be a valuable tool both from a research perspective in comparing them before and after injury and from a clinical perspective in terms of diagnostic and prognostic guidance," said Dr. Gandy. "Having the biomarker information will also help us understand the mechanism of disease development, the reasons for its delayed progression, and the pathway toward effective therapeutic interventions."
Currently, there are no treatments for boxer’s dementia or CTE, but these diseases are preventable. “With more protective equipment, adjustments in the rules of the game, and overall education among athletes, coaches, and parents, we should be able to offer informed consent to prospective sports players and soldiers. With the right combination of identified genetic risk factor, biomarkers, and better drugs, we should be able to dramatically improve the outcome of TBI and prevent the long-term, devastating effects of CTE,” said Dr. Gandy.
(Source: mountsinai.org)
Surgical menopause may prime brain for stroke, Alzheimer’s
Women who abruptly and prematurely lose estrogen from surgical menopause have a two-fold increase in cognitive decline and dementia.
"This is what the clinical studies indicate and our animal studies looking at the underlying mechanisms back this up," said Brann, corresponding author of the study in the journal Brain. “We wanted to find out why that is occurring. We suspect it’s due to the premature loss of estrogen.”
In an effort to mimic what occurs in women, Brann and his colleagues looked at rats 10 weeks after removal of their estrogen-producing ovaries that were either immediately started on low-dose estrogen therapy, started therapy 10 weeks later or never given estrogen.
When the researchers caused a stroke-like event in the brain’s hippocampus, a center of learning and memory, they found the rodents treated late or not at all experienced more brain damage, specifically to a region of the hippocampus called CA3 that is normally stroke-resistant.
To make matters worse, untreated or late-treated rats also began an abnormal, robust production of Alzheimer’s disease-related proteins in the CA3 region, even becoming hypersensitive to one of the most toxic of the beta amyloid proteins that are a hallmark of Alzheimer’s.
Both problems appear associated with the increased production of free radicals in the brain. In fact, when the researchers blocked the excessive production, heightened stroke sensitivity and brain cell death in the CA3 region were reduced.
Interestingly the brain’s increased sensitivity to stressors such as inadequate oxygen was gender specific, Brann said. Removing testes in male rats, didn’t affect stroke size or damage.
Although exactly how it works is unknown, estrogen appears to help protect younger females from problems such as stroke and heart attack. Their risks of the maladies increase after menopause to about the same as males. Follow up studies are needed to see if estrogen therapy also reduces sensitivity to the beta amyloid protein in the CA3 region, as they expect, Brann noted.
Brann earlier showed that prolonged estrogen deprivation in aging rats dramatically reduces the number of brain receptors for the hormone as well as its ability to prevent strokes. Damage was forestalled if estrogen replacement was started shortly after hormone levels drop, according to the 2011 study in the journal Proceedings of the National Academy of Sciences.
The surprising results of the much-publicized Women’s Health Initiative – a 12-year study of 161,808 women ages 50-79 – found hormone therapy generally increased rather than decreased stroke risk as well as other health problems. Critics said one problem with the study was that many of the women, like Brann’s aged rats, had gone years without hormone replacement, bolstering the case that timing is everything.
(Source: eurekalert.org)
Low-Cost ‘Cooling Cure’ Could Avert Brain Damage in Oxygen-Starved Babies
When babies are deprived of oxygen before birth, brain damage and disorders such as cerebral palsy can occur. Extended cooling can prevent brain injuries, but this treatment is not always available in developing nations where advanced medical care is scarce. To address this need, Johns Hopkins undergraduates have devised a low-tech $40 unit to provide protective cooling in the absence of modern hospital equipment that can cost $12,000.
The device, called the Cooling Cure, aims to lower a newborn’s temperature by about 6 degrees F for three days, a treatment that has been shown to protect the child from brain damage if administered shortly after a loss of oxygen has occurred. Common causes of this deficiency are knotting of the umbilical cord or a problem with the mother’s placenta during a difficult birth. In developing regions, untrained delivery, anemia and malnutrition during pregnancy can also contribute to oxygen deprivation.
In a recent issue of the journal Medical Devices: Evidence and Research, the biomedical engineering student inventors and their medical advisors reported successful animal testing of the Cooling Cure prototype. The device is made of a clay pot, a plastic-lined burlap basket, sand, instant ice-pack powder, temperature sensors, a microprocessor and two AAA batteries. To activate it, just add water.
The device could help curtail a serious health problem called hypoxic ischemic encephalopathy, which is triggered by oxygen deficiency in the brain. Globally, more than half of the newborns with a severe form of this condition die, and many of the survivors are diagnosed with cerebral palsy or other brain disorders. The problem is particularly acute in impoverished regions where pregnant women do not have easy access to medical specialists or high-tech hospital equipment. The inventors say Cooling Cure could address this issue.
“The students came up with a neat device that’s easy for non-medical people to use. It’s inexpensive and user-friendly,” said Michael V. Johnston, a Johns Hopkins School of Medicine pediatric neurology professor who advised the undergraduate team. Johnston also is chief medical officer and executive vice president of the Kennedy Krieger Institute, an internationally recognized center in Baltimore that helps children and adolescents with disorders of the brain, spinal cord and musculoskeletal systems.