Rats Injected with Stem Cells: Improved Spinal Injuries?

Researchers at the University of California, San Diego School of Medicine led a study in which rats were injected with one dose of human neural stem cells.  The cell graft improved function and mobility, as well as neuronal regeneration in the rats suffering from acute spinal cord injuries.

According to anesthesiology professor Dr. Martin Marsala and colleagues at the University of California, grafting neural stem cells derived from human fetal spinal cords, and transferring the cells to the rats spinal injury site had many therapeutic benefits.  These benefits range from less spasticity of muscles to the forging of new connections between the injected stem cells and surviving neurons within the rats. The scientists reported that the human stem cells seemed to take root vigorously at the injury site, aiding the recovery process to the point where any cavities or cysts formed at the injury site disappeared as grafted cells were introduced.

The rats received the stem cell injections exactly three days after sustaining the spinal injury, in addition to several drugs that lessened the immune response of the rats so that their bodies would properly accept the stem calls. The stem cells appeared to stimulate the rats’ neuron regeneration, as well as partially replace functionality of lost neurons. The rats had greater control of their paws, and a raised overall quality of life.

With this knowledge in hand, scientists are working to develop neural precursor cells that could potentially become any one of the three cell types found in the nervous system.  This would lead to induced pluripotent stem cells derived from patients, a tool that void the need of immunosuppressants in stem cell therapies.

Sources:

  • Sebastiaan van Gorp, Marjolein Leerink, Osamu Kakinohana, Oleksandr Platoshyn, Camila Santucci, Jan Galik, Elbert A Joosten, Marian Hruska-Plochan, Danielle Goldberg, Silvia Marsala, Karl Johe, Joseph D Ciacci, Martin Marsala. Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation. Stem Cell Research & Therapy, 2013; 4 (5): 57 DOI: 1186/scrt209
  • University of California – San Diego (2013, May 27). Stem cell injections improve spinal injuries in rats. ScienceDaily. Retrieved May 28, 2013, from http://www.sciencedaily.com­ /releases/2013/05/130527231843.htm

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

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Alzheimer’s disease: Molecular Trigger Found?

Scientists at Cambridge’s Department of Chemistry have been able to construct a detailed map that shows how the formation of aberrant proteins in the brain can lead to a build-up so massive that it causes the development of numerous brain-damaging diseases, chief among them being Alzheimer’s.

In 2010, the Alzheimer’s Research Trust found that dementia alone cost the UK economy 23 billion euros, more than the costs of cancer and heart disease combined. Normally, proteins are made up of chemical building blocks known as amino acids, which are joined together in a code ordered by our DNA. New proteins appear as long, thin strips, which are then intricately folded to properly carry out their designated biological function. However, there are points at which the amyloid-beta protein misfolds or unfolds and gets tangled with other newly-made proteins. The tangles stick to one another until they number in the millions, known as amyloid fibrils, and they start the huge deposits of proteins known as plaque, which are so large, they become insoluble.

When the plaque in the brain reaches a critical level, a chain reaction is set off, and new focal points of tendrils form. From these tendrils, a smaller number of proteins, known as toxic oligomers, can easily diffuse through membranes, effectively killing neurons and causing memory loss as well as other dementia symptoms. This new groundbreaking information required scientists to come together, using kinetic experiments with a framework of theory. Master equations, more commonly used in the fields of chemistry and physics, aided researchers in their efforts to better understand Alzheimer’s, and how effectively to fight it.

 

Sources:

 

Source 1)

University of Cambridge (2013, May 20). Molecular trigger for Alzheimer’s disease identified. ScienceDaily. Retrieved May 22, 2013,

 

Source 2)

Samuel I. A. Cohen, Sara Linse, Leila M. Luheshi, Erik Hellstrand, Duncan A. White, Luke Rajah, Daniel E. Otzen, Michele Vendruscolo, Christopher M. Dobson, and Tuomas P. J. Knowles. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1218402110

 

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Toxic Brain Protein: Stopped by Cancer Drug?

At Georgetown University Medical Center, tiny dosage amounts of a Leukemia-inhibiting drug known as nilotinib, were administered to lab mice in a clinical trial meant to examine the effects of the drug on inhibiting the formation of certain proteins in the brain.
These are the same types of proteins that cause accumulation of plaques and decreased cognition in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Lewy Body dementia. Dr. Charbel E-H Moussa, head of the dementia laboratory at Georgetown University, stated that when nilotinib is used to treat CML, it intentionally sends cells into auto-cannibalism, referred to medically as autophagy. The end game of administering this drug to Lukemia patients is the cannibalization of their organelles, and resultantly the death of tumor cells. Moussa’s study broke ground as the first series of experiements testing these types of medications on patients suffering various nueordegenerative disorders. The theory behind using nilotinib was that a small dosage would cause the cells to clean out stores of proteins, but not send them over the edge into a state of autophagy. Mice used in their lab over-expressed alpha-Synuclein, a protein linked to plaque aggregation, and were given one Milligram of nilotinib every two days. Testing of the drug concluded that nilotinib would clean out the toxic brain proteins by causing the cells to go into a state of controlled and partial autophagy , resulting in drastically heightened movement and functionality. At the end of the experiment, Moussa hypothesized that in order for therapy of these neurological diseases to be effective, it must developed and administered as soon as possible. Later usage may result in the retardation of extracellular formation, as well as the accumulation of intracellular proteins such as Lewy bodies, which job it was for nilotinib to remove in the first place.
Sources:
1) Michaeline L. Hebron, Irina Lonskaya, and Charbel E.-H. Moussa. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson’s disease models. Hum. Mol. Genet., May 10, 2013 DOI: 10.1093/hmg/ddt192
2) Georgetown University Medical Center (2013, May 10). Cancer drug prevents build-up of toxic brain protein. ScienceDaily. Retrieved May 22.

By Lauren Horne

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit http://www.rfdn.org.

Key to Treating Alzheimer’s: Brain Garbage Truck?

Researchers at the University of Rochester Medical Center point to a newly discovered system, which processes and removes waste in the brain, as a possible key to treating neurological disorders such as Alzheimer’s disease.
Modern scientists are beginning to build on the late-1800s understanding of the “blood-brain barrier” with new incoming knowledge of the brain’s dynamics for removing waste, recently dubbed the glymphatic system. The lymphatic system, a circulatory network of organs and vessels, removes waste materials from the rest of the body, but does not extend to the brain. Scientists began to postulate about how the brain kept house, one of the main issues being that there is no trace of any such system within brain tissue samples. But new technology known as two-photon microscopy allowed scientists to delve deeper into the living brain for study. Coupling the new tech with mice brains, Dr. Maiken Nedergaard, co-director of the URMC for Transitional Medicine, and her colleagues were able to observe and document the extensive waste system of the brain.
The brain is surrounded by a membrane, called the arachnoid, that is flushed with cerebral spinal fluid (CSF) which flows through the brain on the same pathways as the arteries reaching the brain. CSF is drawn into the brain tissue through a system of conduits controlled by glia, support cells. CSF is moved through the brain at high speeds, picking up excess proteins and waste products along the way. The fluid and waste are channeled into a system which parallels veins and transports the byproducts from the brain, down the spinal column, and to the liver where everything is ultimately broken down. With this discovery, scientists can delve into the research regarding how to apply this knowledge in the treatment of neurological disorders. This find may prove especially beneficial in the case of Alzheimer’s, a disease whose hallmark is the build-up of beta amyloid plaques. Further research would test whether manipulating glia to ramp up waste removal would better prevent the build-up of excess proteins such as beta amyloid.
Source:
1) University of Rochester Medical Center (2013, June 27). Brain’s ‘garbage truck’ may hold key to treating Alzheimer’s and other disorders. ScienceDaily. Retrieved July 1, 2013, from http://www.sciencedaily.com/releases/2013/06/130627142402.htm

By Lauren Horne

Antidepressant May Slow Progression of Alzheimer’s Disease

According to research by the Washington University School of Medicine, published in Science Translational Medicine, a common antidepressant can reduce the production of brain plaques.

 

Brain plaques correlate closely with memory problems and other cognitive impairments caused by Alzheimer’s disease. Stopping plaque buildup is believed to help halt the mental decline of Alzheimer’s patients. Scientists found the antidepressant citalopram stopped the growth of plaques in a mouse model of the disease. The research also found, in young adult humans who were cognitively healthy, that a single dose of the antidepressant lowered production of amyloid beta by thirty-seven percent. The researchers stress that while the results may be promising, any treatment at this point is premature.

 

Levels of amyloid beta, a protein produced by normal brain activity, rise in the brains of patients with Alzheimer’s, and eventually clump together to form plaques. Most antidepressants keep serotonin circulating in the brain, and this study was born from the theory that serotonin helps reduce plaque levels in cognitively health individuals.

 

For this research, scientists gave citalopram to older mice with brain plaques. They used two-photon imaging to track the growth of plaques in the mice for twenty-eight days. The results showed a rate of formation of new plaques decreased by seventy-eight percent. In a second experiment, the scientists gave citalopram to twenty-three people cognitively healthy people aged eighteen to fifty. Spinal fluid from the participants over the next day showed a thirty-seven percent drop in amyloid beta production.

 

Sources:

  1. Sheline YI, West T, Yarasheski K, Swarm R, Jasielec MS, Fisher JR, Ficker WD, Yan P, Xiong C, Frederiksen C, Grzelak MV, Chott R, Bateman RJ, Morris JC, Mintun MA, Lee J-M, Cirrito JR. An antidepressant decreases CSF Ab production in healthy individuals and in transgenic AD mice. Science Translational Medicine, online May 14, 2014.
  2. Washington University in St. Louis. (2014, May 14). Antidepressant may slow Alzheimer’s disease. ScienceDaily. Retrieved May 16, 2014 from sciencedaily.com/releases/2014/05/140514142326.htm

By Emma Henson

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit www.rfdn.org.

Amino Acids Improve Sleep in Mice with Traumatic Brain Injury

A study by Oregon Health and Science University, published in Science Translational Medicine, discovered a way to fix sleep disturbances in mice with traumatic brain injury. These results are important, because people commonly experience long-term and severe sleep and wakefulness issues after suffering concussions, a mild form of traumatic brain injury. The research hinged on feeding mice branched chain amino acids, something humans naturally produce from food. Dr. Miranda Lim, first author of the study, hopes that further studies will uphold the results found, and a dietary supplement prescribed as a viable therapy for concussions could be developed.

 

Nearly two million people in the US suffer traumatic brain injury every year, and nearly 72% have sleep disturbances. Sleep problems are not only frustrating, but physically harmful. The lack of rest impairs attention and memory formation for TBI patients, who already have a higher rate of functional disability and higher cost of rehabilitation. Treatments to remedy the dangerous swelling occurring after TBI exist, while underlying brain damage evident in sleep impairment as well as learning patterns remains without treatments.

 

The study compared mice with mild TBI to uninjured mice, and found the injured mice much less capable of staying awake for sustained periods of time. Scientists pinned this on underactive orexin neurons, meant to maintain wakefulness, mirroring spinal fluid evidence of human TBI patients. The scientists gave the injured mice a dietary therapy of branched chain amino acids; the building blocks of neurotransmitters, chemicals released by neurons in the brain. The results showed a restoration of normal orexin levels, and improved wakefulness. This offers a proof-of-principle for dietary intervention as a treatment for TBI, and hopefully an avenue to help brain-injured patients regain cognitive functions.

 

Source:

  • M. Lim, J. Elkind, G. Xiong, R. Galante, J. Zhu, L. Zhang, J. Lian, J. Rodin, N. N. Kuzma, A. I. Pack, A. S. Cohen. Dietary Therapy Mitigates Persistent Wake Deficits Caused by Mild Traumatic Brain Injury. Science Translational Medicine, 2013; 5 (215): 215ra173 DOI: 10.1126/scitranslmed.3007092
  • Oregon Health & Science University (2013, December 11). Dietary amino acids improve sleep problems in mice with traumatic brain injury. ScienceDaily. Retrieved January 7, 2014, from http://www.sciencedaily.com­ /releases/2013/12/131211185331.htm

By Emma Henson

The Roskamp Institute is a 501(c)3 research facility dedicated to translating the efforts of its qualified research staff into real-world results for those suffering from neurological diseases. To learn more about our programs and to get information about donating, visit www.rfdn.org.