Category: Brain Injury

 Each year, approximately 150,000 Canadians have a transient ischemic attack (TIA), sometimes known as a mini-stroke. New research published January 28 in Stroke, the journal of the American Heart Association shows these attacks may not be transient at all. They in fact create lasting damage to the brain.

The stroke research team, led by Dr. Lara Boyd, physical therapist and neuroscientist with the Brain Research Centre at Vancouver Coastal Health and the University of British Columbia, studied 13 patients from the Stroke Prevention Clinic at Vancouver General Hospital and compared them against 13 healthy study participants. The TIA subjects had all experienced an acute episode affecting motor systems, but had symptoms resolved within 24 hours. The patients were studied within 14-30 days of their episode, and showed no impairment through clinical evaluation or standard imaging (CT or MRI). Participants then underwent a unique brain mapping procedure using transcranial magnetic stimulation (TMS) with profound results.

"What we found has never been seen before," says Dr. Boyd, who also holds the Canada Research Chair in Neurobiology of Motor Learning at UBC. "The brain mapping capabilities of the TMS showed us that TIA is actually causing damage to the brain that lasts much longer than we previously thought it did. In fact, we are not sure if the brain ever recovers."

In the TIA group, brain cells on the affected side of the brain showed changes in their excitability — making it harder for both excitatory and inhibitory neurons to respond as compared to the undamaged side and to a group of people with healthy brains. These changes are very concerning to the researchers as they show that TIA is likely not a transient event.

A transient ischemic attack is characterized as a brief episode of blood loss to the brain, creating symptoms such as numbness or tingling, temporary loss of vision, difficulty speaking, or weakness on one side of the body. Symptoms usually resolve quickly and many people do not take such an episode seriously. However, TIAs are often warning signs of a future stroke. The risk of a stroke increases dramatically in the days after an attack, and the TIA may offer an opportunity to find a cause or minimize the risk to prevent the permanent neurologic damage that results because of a stroke.

"These findings are very important," says Dr. Philip Teal, head of the Stroke Prevention Clinic at VGH and co-author of the study. "We know that TIA is a warning sign of future stroke. We treat every TIA as though it will result in a stroke, but not every person goes on to have a stroke. By refining this brain mapping technique, our hope is to identify who is most at risk, and direct treatment more appropriately."

Scientists at The Rehabilitation Institute of Chicago (RIC) report that, thanks to improvements in technology and data analysis, our understanding of the functional principles that guide the development and operation of the brain could improve drastically in the next few years. The advances could herald a neuroscientific revolution, much as increasing processor speeds paved the way for the computing revolution of the last half century.

In the February, 2011 issue of Nature Neuroscience, the researchers, Dr. Ian H. Stevenson and Dr. Konrad P. Kording, performed a meta-analysis of 56 studies conducted since the 1950s (the advent of multi-electrode recordings) in which the activity of neurons was recorded in animals or humans. They found that the number of simultaneously recorded single neurons has grown exponentially since the 1950s, doubling approximately every seven years.

The researchers likened the progress in neuronal recording techniques to Moore's law, which describes the exponential growth of processing speed that has doubled approximately every two years, making computers smaller and technology accessible to more people.

"As it becomes easier for us to access and interpret information coming from the brain, we will be able to better help those with disabilities and conditions of the nervous system," said Dr. Kording. "Our goal is to take what we are learning about how and why the brain works so we can quickly and successfully use it to help patients. By decoding how neurons communicate with each other, we may one day be able to restore connections by conditioning different neurons to talk to each other, or to talk to each other in different ways, thereby restoring ability in our patients."

The "firing" or "spiking" of a neuron is really a signal sent along a gradient to other neurons and throughout the entire nervous system. These signals send messages and convey important information, including representations about the world and messages that control our behaviors and actions.

According to Dr. Kording, "Recording of only a single neuron at a time was possible in the late 1950s. Now, researchers can record activity from hundreds of neurons simultaneously, gathering valuable information about when and why neurons fire or do not fire."

In patients with conditions caused by lost connections in the brain, such as stroke or spinal cord injury, information from the brain sent via neurons cannot get relayed to certain limbs or parts of the body. Researchers at RIC are using data from neurons to pioneer research designed to restore connections and ability using novel technologies. In fact, RIC researchers recently reported that they have identified novel ways of potentially re-routing the flow of information in the nervous system using stimulation technology. Currently, RIC researchers are on the cutting-edge of exploring the use of novel brain-machine interface, functional electronic stimulation and virtual reality technology to restore function in individuals suffering from paralysis caused by spinal cord injuries or stroke.

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Journal Reference:

1. Ian H Stevenson, Konrad P Kording. How advances in neural recording affect data analysis. Nature Neuroscience, 2011; 14 (2): 139 DOI: 10.1038/nn.2731

Strokes are a leading cause of mortality and adult disability. Those that involve intracerebral hemorrhage (bleeding in the brain) are especially deadly, and there are no effective treatments to control such bleeding. Moreover, diabetes and hyperglycemia (high blood glucose levels) are associated with increases in bleeding during hemorrhagic stroke and worse clinical outcomes.

But Joslin Diabetes Center researchers now have identified one key player that contributes to this increased bleeding, a discovery that may pave the way toward treatments that minimize adverse stroke outcomes both for people with pre-existing diabetes and those with hyperglycemia identified at the time of stroke.

Studies in the lab of Joslin Investigator Edward Feener, Ph.D., pinpointed a new mechanism involving a protein called plasma kallikrein that interferes with the normal clotting process in the brain following blood vessel injury with diabetes. Their work is reported online in the journal Nature Medicine.

The scientists began by injecting a small amount of blood into the brains of rats with diabetes and of control animals without diabetes. The difference was dramatic — the diabetic animals bled over a much greater area of the brain.

Work in the Feener lab had previously implicated plasma kallikrein in diabetic eye complications. When the experimenters pre-treated the diabetic animals with a molecule that inhibits the protein's effects, brain damage from the blood injections dropped to levels similar to that in the control animals. Conversely, when pure plasma kallikrein was injected into the brain, it produced little impact on the control animals but rapidly increased major bleeding in the animals with diabetes.

Further studies by the Joslin researchers showed that normalizing blood glucose levels in diabetic animals could block the effect from plasma kallikrein, and that rapidly inducing hyperglycemia in control animals mimicked the effects of diabetes on brain hemorrhage. This suggests that high blood sugar at the time of brain hemorrhage, rather than diabetes per se, is responsible for the increased bleeding.

"Given the prevalence of strokes and the damage they inflict, these findings are exciting because they suggest the possibility that rapid control of blood sugar levels may provide an opportunity to reduce intracerebral hemorrhage, which is a clinical situation that has very limited treatment options," says Dr. Feener, who is also an associate professor of medicine at Harvard Medical School. "This work could have broad implications since about half of patients with acute hemorrhagic stroke have hyperglycemia, whether or not they have pre-existing diabetes."

The work also raises the possibility of developing drugs that target plasma kallikrein and may provide protective measures in people with diabetes or others at high risk for stroke. Such drugs might also prove useful for patients suffering from the more common ischemic strokes, which usually begin as blocked vessels in the brain but can transform into hemorrhages.

Surprisingly, while plasma kallikrein has been studied for decades, the Joslin scientists found that the protein boosts brain bleeding through a previously unknown mechanism — by blocking platelet activation near damaged blood vessels.

Joslin's Jia Liu and Ben-Bo Gao were co-lead authors on the Nature Medicine paper. Other contributors include Joslin's Allen Clermont, and Price Blair and Robert Flaumenhaft of Beth Israel Deaconess Medical Center, and Tamie Chilcote and Sukanto Sinha of ActiveSite Pharmaceuticals. Lead funding came from the National Institutes of Health and the American Heart Association.

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Journal Reference:

1. Jia Liu, Ben-Bo Gao, Allen C Clermont, Price Blair, Tamie J Chilcote, Sukanto Sinha, Robert Flaumenhaft, Edward P Feener. Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nature Medicine, 2011; DOI: 10.1038/nm.2295

The anti-diuretic hormone "vasopressin" is released from the brain, and known to work in the kidney, suppressing the diuresis. Now, a Japanese research team led by Professor Yasunobu Okada, Director-General of National Institute for Physiological Sciences (NIPS), and Ms. Kaori Sato, a graduate student of The Graduate University for Advanced Studies, has clarified the novel function of "vasopressin" that works in the brain, as well as in the kidney via the same type of the vasopressin receptor, to maintain the size of the vasopressin neurons.

It might be a useful result for clarification of the condition of cerebral edema which swells along with the brain trauma or the cerebral infarction, and for its treatment method development. This result of the study is reported in the Science Signaling magazine.

The research team focused on the vasopressin neurons which exist in a hypothalamus of the brain. The vasopressin is essentially released from the vasopressin neurons into blood circulation and acts on the kidney as anti-diuretic, when the blood plasma becomes more concentrated. In contrast, they ascertained that the vasopressin neurons release the vasopressin into the brain, not in blood, when the surrounding body fluid becomes more diluted than usual. Usually, the more diluted the body fluid becomes, the bigger the neuronal cell swells. However, their finding shows that the vasopressin in the brain maintains the size of the vasopressin neurons even when the body fluid becomes more diluted. In addition, it was clarified that the vasopressin sensor protein (receptor) which was currently considered to be only in the kidney, was related to this function in the brain.

This study became possible by labeling vasopressin neurons of the rat brain hypothalamus with green fluorescent protein (GFP)．(The transgenic rat was developed by Professor Yoichi Ueta; University of Occupational and Environmental Health, Japan.)

Professor Okada says that "It is a surprising result that the same type of the vasopressin receptor as the kidney exists in the brain and the vasopressin works on it. It can be expected to clarify the condition of cerebral edema which swells along with the brain trauma or the cerebral infarction, and to develop its treatment method.

This result is supported by Grants-in-Aid for Scientific Research, the MEXT, Japan.

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Journal Reference:

1. K. Sato, T. Numata, T. Saito, Y. Ueta, Y. Okada. V₂ Receptor-Mediated Autocrine Role of Somatodendritic Release of AVP in Rat Vasopressin Neurons Under Hypo-Osmotic Conditions. Science Signaling, 2011; 4 (157): ra5 DOI: 10.1126/scisignal.2001279

An Inserm research team in Toulouse, led by Dr Stein Silva (Inserm Unit 825 "Brain imaging and neurological handicaps"), working with the "Modelling tissue and nociceptive stress" Host Team (MATN IFR 150), were interested in studying the illusions described by many patients under regional anaesthetic. In their work, to be published in the journal Anesthesiology, the researchers demonstrated that anaesthetising an arm affects brain activity and rapidly impairs body perception.

The ultimate aim of the work is to understand how neuronal circuits are reorganised at this exact moment in time and to take advantage of anaesthesia to reconfigure them correctly following trauma. This would allow anaesthetic techniques to be used in the future to treat pain described by amputated patients in what are known as "phantom limbs."

Neuroscience research in recent years has shown that the brain is a dynamic structure. Phenomena such as learning, memorising or recovery from stroke are made possible by the brain's plastic properties. Brain plasticity does not, however, always have a beneficial effect.

For example, some amputated patients suffering from chronic pain (known as phantom limb pain) feel as though their missing limb were "still there." Such "phantom limb" illusions are related to the appearance in the brain of incorrect representations of the missing body part.

Persons under regional anaesthetic describe these very same false images.

Based on these observations, Inserm's researchers wished to discover whether anaesthesia could, in addition to fulfilling its primary function, induce comparable phenomena in the brain. If this were so, anaesthetics could be used as new therapeutic tools capable of modulating brain activity.

With this in mind, a team headed by Dr Stein Silva monitored 20 patients who were to have one of their arms anaesthetised before surgery. The patients were shown 3D images of the hand, shot from different angles, and their ability to distinguish the right hand from the left was assessed. Results showed how anaesthesia affected the patients' ability to perceive their body correctly.

The researchers observed three phenomena based on these tests:

• All the patients described false sensations in their arm (swelling, difference in size and shape, imagined posture).
• In general, patients under anaesthetic took longer to distinguish between a left and right hand and made far more mistakes than persons not under anaesthetic.
• The best results were obtained when the anaesthetised limb was visible.

In other words, anaesthetising the hand (peripheral deafferentation ) modifies brain activity and rapidly changes the way we perceive the outside world and our own body. The teams are now using functional brain imaging to characterise the regions concerned in the brain. They also hope that it will be possible to use anaesthesia for therapeutic purposes in the future by modulating post-lesional plasticity (chronic pain in amputated patients, improved recovery in those suffering from brain lesions).

Inserm researcher Stein Silva, an anaesthetist and the chief author of the study, believes that it will no doubt be necessary to develop new anaesthetic techniques to inhibit or directly stimulate the brain images associated with painful phenomena.

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Journal Reference:

1. Stein Silva, Isabelle Loubinoux, Michel Olivier, Benoîmt Bataille, Olivier Fourcade, Kamran Samii, Marc Jeannerod, Jean-Francois Démonet. Impaired Visual Hand Recognition in Preoperative Patients during Brachial Plexus Anesthesia. Anesthesiology, 2011; 114 (1): 126 DOI: 10.1097/ALN.0b013e31820164f1

A new study identifies a molecule that is a critical regulator of neuron survival after ischemic brain injury. The research, published in the January 13 issue of the journal Neuron, may lead to new therapies that reduce damage after a stroke or other injuries that involve an interruption in blood supply to the brain.

Ischemic brain injury is damage caused by a restriction in blood supply. Neuronal death after an interruption in the supply of oxygen and glucose involves a complex cascade of pathological events and, although previous research has identified key signaling pathways involved in neuronal death, factors contributing to neuronal survival after ischemia are not well understood. "Although a number of molecules and compounds conferring resistance to ischemic stresses have been identified, they have failed to be protective in clinical trials despite promising preclinical data," explains senior study author, Dr. Kazuo Kitagawa from the Osaka University Graduate School of Medicine in Japan.

Earlier research implicated a molecule called cAMP responsive elements binding protein (CREB) in the protection of neurons after ischemia. CREB is known to regulate many different genes and plays a role in diverse physiological processes. In the current study, Dr. Kitagawa, coauthor Dr. Hiroshi Takemori, and their colleagues found that salt-inducible kinase 2 (SIK2) was expressed in neurons at high levels but was reduced after ischemic injury. They went on to show that SIK2 suppressed CREB-mediated gene expression after oxygen and glucose deprivation and that neuronal survival after ischemia was significantly increased in mice that were lacking SIK2.

"We found that oxygen and glucose deprivation induced SIK2 degradation concurrently with regulation of the CREB-specific coactivator transducer of regulated CREB activity 1 (TORC1), resulting in activation of CREB and its downstream targets," says Dr. Takemori. These findings suggest that SIK2 plays a critical role in neuronal survival and may have clinical applications. "Our results suggest that the SIK2-TORC1-CREB signaling pathway may serve as a potential therapeutic target for promoting the survival of neurons," concludes Dr. Kitagawa. "These findings also raise new opportunities for the development of novel therapeutics."

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Journal Reference:

1. Tsutomu Sasaki et al. SIK2 Is a Key Regulator for Neuronal Survival after Ischemia via TORC1-CREB. Neuron, Volume 69, Issue 1, 13 January 2011, Pages 106-119 DOI: 10.1016/j.neuron.2010.12.004

 Zinc ions released at the junction between two neurons (called a synapse) are important signals, but when too much zinc accumulates, cells become dysfunctional or die.

Researchers in the Blue Bird Circle Developmental Neurogenetics Laboratory in the department of neurology at Baylor College of Medicine have discovered that zinc enters cells through specialized protein gates known as ZIP transporters, and removing these ZIP proteins from cells in the hippocampus (an area of the brain that facilitates storing and retrieving memory) significantly protects them from injury. The results are published in the latest issue of Journal of Neuroscience.

"These findings pave the way for the development of a new type of neuroprotective medicine for conditions such as seizures, stroke, brain trauma and other neurodegenerative disorders," said Dr. Jeffrey L. Noebels, professor of neurology, neuroscience and molecular and human genetics at BCM as well as director of the Blue Bird Circle Developmental Neurogenetics Laboratory. Many laboratories are looking for such drugs, and this provides an important clue.

Large amounts of synaptic zinc are found in the hippocampus. However, this brain circuit is a common site for epileptic seizures, and hippocampal cells are extremely vulnerable to damage during a prolonged brain "storm," as seizures are sometimes called. Since seizures activate many other molecules that may potentially injure cells and also are accompanied by a cutoff off of oxygen and glucose to nerves, the contribution of excessive zinc released during the seizure has not been clear.

Zinc finds its way into brain cells through multiple entry sites: ion channels, glutamate receptors, and a family of special uptake transporters known as ZIP proteins. Dr. Jing Qian, assistant professor of neurology at BCM, used optical imaging techniques in brain slices to demonstrate that most zinc enters neurons through two ZIP proteins, ZIP1 and ZIP3. Qian also found that the entry is accelerated by neuronal firing.

When he analyzed cellular damage following prolonged seizures in mice that were genetically engineered to be missing the two ZIP genes, he found that a crucial group of hippocampal neurons are remarkably undamaged following even severe seizures lasting six hours or longer.

"This study is exciting, because for the first time we have shown that reducing zinc entry alone, without removing it from the diet or interfering with its other important functions, is an effective way to protect brain cells from damage due to seizures, and probably a variety of other insults to the brain," said Noebels. "We now believe these ZIP proteins represent new and important molecular targets for the development of drugs that can specifically reduce zinc entry and protect memory circuits in the brain from damage."

Others who took part in the research include Kaiping Xu, Jong Yoo, and Tim T. Chen, all of BCM and Glen Andrews of the University of Kansas Medical Center in Kansas City, Kansas.

Funding for this research came from the National Institutes of Neurological Disorders and Stroke and the Blue Bird Circle Pediatric Neurology Research Foundation.

Noebels holds the Cullen Trust for Health Care Endowed Chair.

A small area deep in the brain called the perirhinal cortex is critical for forming unconscious conceptual memories, researchers at the UC Davis Center for Mind and Brain have found.

The perirhinal cortex was thought to be involved, like the neighboring hippocampus, in "declarative" or conscious memories, but the new results show that the picture is more complex, said lead author Wei-chun Wang, a graduate student at UC Davis.

The results were published Dec. 9 in the journal Neuron.

We're all familiar with memories that rise from the unconscious mind. Imagine looking at a beach scene, said Wang. A little later, someone mentions surfing, and the beach scene pops back into your head.

Declarative memories, in contrast, are those where we recall being on that beach and watching that surf competition: "I remember being there."

Damage to a structure called the hippocampus affects such declarative "I remember" memories, but not conceptual memories, Wang said. Neuroscientists had previously thought the same was true for the perirhinal cortex, which is located immediately next to the hippocampus.

Wang and colleagues carried out memory tests on people diagnosed with amnesia, who had known damage to the perirhinal cortex or other brain areas. They also carried out functional magnetic resonance imaging (fMRI) scans of healthy volunteers while they performed memory tests.

In a typical test, they gave the subjects a long list of words, such as chair, table or spoon, and asked them to think about how pleasant they were.

Later, they asked the subjects to think up words in different categories, such as "furniture."

Amnesiacs with damage to the perirhinal cortex performed poorly on the tests, while the same brain area lit up in fMRI scans of the healthy control subjects.

The study helps us understand how memories are assembled in the brain and how different types of brain damage might impair memory, Wang said. For example, Alzheimer's disease often attacks the hippocampus and perirhinal cortex before other brain areas.

Co-authors on the study are Andy Yonelinas, professor of psychology and at the Center for Mind and Brain; Charan Ranganath, professor at the Center for Neuroscience; former UC Davis graduate student Michele Lazzara, now project coordinator at the University of Illinois at Chicago; and Robert Knight, professor of psychology at UC Berkeley.

The work was funded by the National Institutes of Health.

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Journal Reference:

1. Wei-Chun Wang, Michele M. Lazzara, Charan Ranganath, Robert T. Knight, Andrew P. Yonelinas. The Medial Temporal Lobe Supports Conceptual Implicit Memory. Neuron, 2010; 68 (5): 835 DOI: 10.1016/j.neuron.2010.11.009

 When computerized neuropsychological testing is used, high school athletes suffering from a sports-related concussion are less likely to be returned to play within one week of their injury, according to a study in The American Journal of Sports Medicine. Unfortunately, concussed football players are less likely to have computerized neuropsychological testing than those participating in other sports.

A total of 544 concussions were recorded by the High School Reporting Information Online surveillance system during the 2008-2009 school year. Researchers looked at each of those instances to see what caused the injury, what sport was being played, what symptoms were experienced, what type of testing was used, and how soon the athletes returned to play. When looking at the causes and duration of concussions, the research found that:

• 76.2% of the concussions were caused by contact with another player, usually a head-to-head collision
• 93.4% of concussions caused a headache; 4.6% caused loss of consciousness
• 83.4% experienced resolution of their symptoms within a week, while 1.5% had symptoms that lasted longer than a month

Computerized neuropsychological testing was used in 25.7% of concussions, and in those cases, athletes were less likely to return to play within one week, than those athletes for whom it was not used. Interestingly, however, researchers found that injured football players were less likely to be examined using the computerized neuropsychological testing than injured athletes participating in other sports.

"Although it is now recognized as one of 'the cornerstones of concussion evaluation,' routine neuropsychological testing in the setting of sports-related concussion is a relatively new concept," write the authors, William P. Meehan III, MD, Pierre d'Hemecourt, MD, and R. Dawn Comstock, PhD. "This is the first study, of which we are aware, to query the use of computerized neuropsychological testing in high school athletes using a large, nationally representative sample."

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Journal Reference:

1. W. P. Meehan, P. d'Hemecourt, R. D. Comstock. High School Concussions in the 2008-2009 Academic Year: Mechanism, Symptoms, and Management. The American Journal of Sports Medicine, 2010; 38 (12): 2405 DOI: 10.1177/0363546510376737

A synthetic derivative of the curry spice turmeric, made by scientists at the Salk Institute for Biological Studies, dramatically improves the behavioral and molecular deficits seen in animal models of ischemic stroke and traumatic brain injury (TBI). Two new studies suggest that the novel compound may have clinical promise for these conditions, which currently lack good therapies.

Ischemic stroke is the leading cause of disability and the third leading cause of death of older people in the United States, while TBI is the leading cause of death and disability in both civilians and military personnel under the age of 45; in particular, it is the major cause of disability in veterans returning from Iraq and Afghanistan. In both conditions, those who survive frequently have serious behavioral and memory deficits. The only FDA-approved treatment for stroke is tissue plasminogen activator (TPA), which is effective only in about 20 percent of cases. There is no clinically documented treatment for TBI.

In earlier studies, David R. Schubert. Ph.D., and Pamela Maher, Ph.D., in the Salk Cellular Neurobiology Laboratory had developed a series of new compounds using a novel drug discovery paradigm that starts with natural products derived from plants; it then calls for selecting synthetic derivatives that show efficacy in multiple assays testing protection against various aspects of the nerve cell damage and death that occur in brain injuries and in age-associated neurodegenerative diseases. One compound, called CNB-001, which was derived from curcumin, the active ingredient in the spice turmeric, proved highly neuroprotective in all of the assays; it also enhanced memory in normal animals.

While the Salk group has a great deal of expertise in age-associated neurological diseases such as Alzheimer's, they do not run animal models of TBI and stroke. "To test the prediction that drugs from our new drug discovery scheme will work in multiple models of CNS disease and trauma," Schubert explains, "we undertook a series of experiments to assay the drugs in collaboration with researchers at Cedars-Sinai and UCLA, who are leaders in the fields of stroke and TBI, respectively, and appreciate the potential for therapeutics based on natural products and their derivatives."

Employing the same animal model of stroke that was used to develop TPA, Paul Lapchak, Ph.D., of the Department of Neurology at the Burns and Allen Research Institute at Cedars-Sinai Medical Center in Los Angeles, collaborated with Schubert's team in a study that showed that CNB-001 was at least as effective as TPA in preventing the behavioral deficits caused by stroke. The study, published in the Dec. 2, 2010 edition of the Journal of Neurochemistry, also demonstrated that unlike TPA, which reduces clotting in the blood vessels of the brain, the Salk compound has a direct protective effect on nerve cells within the brain. Maher has found that it maintains specific cell signaling pathways required for nerve cell survival.

Similarly, in a study to be published in early 2011 in Neurorehabilitation and Neural Repair, Fernando Gomez-Pinilla, Ph.D., and his colleagues in the Department of Physiological Science and Division of Neurosurgery at the University of California, Los Angeles used a rodent model of TBI to demonstrate that CNB-001 dramatically reversed the behavioral deficits in both locomotion and memory that accompany the brain injury. As with stroke, CNB-001 was again found to maintain the critical signaling pathways required for nerve cell survival, as well as the connections between nerve cells that are lost with the injury.

The results of these two studies, which used two distinct models of brain injury, indicate that the Salk compound has clinical potential in conditions where there is currently no effective treatment.

"Existing drug therapies for complex neurological conditions such as stroke and Alzheimer's disease target only one aspect of the condition, while in fact many different factors contribute to the pathology," observes Schubert. "In the drug discovery program our lab uses at Salk, drug candidates must show efficacy in tissue culture models of several aspects of the condition before they are introduced into animal models. We believe that this approach is making an important difference in the discovery of effective drugs."

In related work, Maher used the same drug discovery paradigm to identify a compound that is effective in animal models of Huntington's disease. "Although these brain disorders appear very different, they share common changes in the nerve cells, which suggests that compounds that prevent these changes will be effective in multiple disorders," she notes.

In addition to Schubert and Gomez-Pinilla, Aiguo Wu, Ph.D., and Zhe Ying of the UCLA Department of Physiological Science contributed to the TBI study.

Both studies were supported by the National Institutes of Health; Gomez-Pinilla's study received additional funding from the Craig Neilsen Foundation.

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Journal Reference:

1. Paul A. Lapchak, David R. Schubert, Pamela A. Maher. Delayed treatment with a novel neurotrophic compound reduces behavioral deficits in rabbit ischemic stroke. Journal of Neurochemistry, 2011; 116 (1): 122 DOI: 10.1111/j.1471-4159.2010.07090.x