NRx (formerly known as Net Results Express) is UHN's monthly research e-newsletter. Through NRx you can read about ongoing research at our five research institutes, the Ontario Cancer Institute (OCI), the Toronto General Research Institute (TGRI), the Toronto Western Research Institute (TWRI), the Toronto Rehabilitation Institute (TRI) and the Techna Institute (Techna).

In this issue you can read about research in:

• The regulation of blood cell development
  
• Preventing the rejection of cardiac stem cell transplants
  
• Mind wandering and the perception of pain
  
• Measuring brain waves
  
• Reducing the production of glucose in the liver
• Protection of cognitive function after brain injury

We hope that you will find NRx informative. If you have feedback or questions, please contact www@uhnresearch.ca.

Christopher J. Paige, PhD, FCAHS
Vice President, Research
University Health Network

Heart attacks cause irreparable damage to cardiac tissue leading to the formation of scar tissue that does not function normally.

Mesenchymal stem cells (MSCs) have been found to improve heart function when they are transplanted into patients with injured hearts. However, MSCs from older patients have limited capacity for tissue regeneration and restoration of heart function. Stem cells from young donors have a greater regenerative capacity and may be better candidates for clinical application. Unfortunately, these allogeneic stem cells—referred to as allogeneic because they come from a genetically non-identical donor—can only evade the immune system early after implantation and are eventually killed by the recipient’s immune cells.

In an attempt to improve the survival of transplanted MSCs and increase their potential to repair damaged hearts, TGRI Senior Scientist Dr. Ren-Ke Li and his collaborators have examined which factors might help MSCs maintain their ability to not activate the recipient’s immune system. Dr. Li and his team found that a protein known as prostaglandin E2 (PGE2) is able to induce the expression of proteins that suppress immune responses. They were was also able to show that when PGE2 is slowly released at the site of MSC injection, through the use of a biodegradable gel, the transplanted stem cells survive longer and improve heart function.

Explains Dr. Li, "We demonstrated that maintaining PGE2 levels prevents the rejection of MSCs and leads to improved heart function. Hopefully, these findings will be useful in developing allogeneic stem cell-based cardiac therapies that can improve the current standard of care for cardiovascular diseases."

This work was supported by the Canadian Institutes of Health Research. RK. Li is a Tier I Canada Research Chair in Cardiac Regeneration.

Preserving prostaglandin e2 level prevents rejection of implanted allogeneic mesenchymal stem cells and restores postinfarction ventricular function. Dhingra S, Li P, Huang XP, Guo J, Wu J, Mihic A, Li SH, Zang WF, Shen D, Weisel RD, Singal PK, Li RK. Circulation. 2013 September 10. [Pubmed abstract]

Changes in neural oscillations can accompany a number of neurological diseases including epilepsy, schizophrenia and Parkinson’s disease.

Measurable electrical neural oscillations are signals that represent the activity of the central nervous system. They communicate information between regions of the brain. Currently, the best methods of studying the brain circuitry responsible for generating neural oscillations come from animal models—no equivalent human models exist.

TWRI Affiliate Scientist Dr. Taufik Valiante, in collaboration with TWRI Affiliate Scientist Dr. Liang Zhang and TWRI Senior Scientist Dr. Peter Carlen, has demonstrated a new technique that can maintain human brain samples outside the body—these sections of brain tissue can generate neural oscillations similar to those observed in the living brain. These samples, known as neocortical slices, are obtained from a surgical procedure that removes tissue from the neocortex of patients with epilepsy.

Two types of neural oscillations were observed in the neocortical slices—theta oscillations and high gamma waves—which are thought to be involved in a number of cognitive and motor functions. These oscillations are difficult to generate in existing animal models, and thus have not been extensively studied in neocortical slices. Dr. Valiante says, "We observed that these two waves were coupled together, and to one another, suggesting a novel type of communication between layers of the neocortex. This technique will allow us to better investigate the circuitry of the human brain."

This work was supported by the Canadian Institutes of Health Research.

In vitro recordings of human neocortical oscillations. Florez CM, McGinn RJ, Lukankin V, Marwa I, Sugumar S, Dian J, Hazrati LN, Carlen PL, Zhang L, Valiante TA. Cerebral Cortex. 2013 September 17. [Pubmed abstract]

Memory loss is often the result of brain injury and has been linked to damage of the brain structure known as the hippocampus (in red above).

Traumatic brain injury (TBI) is a leading cause of injury-related death and disability in North America. Currently, TBI is seen as "non-progressive"—thus, after injury, it is expected that patients should exhibit steady cognitive improvements and stabilization of brain function. This view is now being challenged by studies that show that progressive loss of brain matter may occur in the chronic stages of injury; furthermore, some patients are known to experience chronic loss of cognitive function as well. Given the possibility that TBI may have long-term risks, new approaches are required to minimize loss of brain function in the chronic stages of injury.

TRI Senior Scientist Dr. Robin Green has been studying this new conceptualization of brain injury and has recently published encouraging findings. Examining whether loss of brain matter could be offset by environments that stimulate high levels of mental, physical and social activity after TBI, Dr. Green's team examined 25 patients with moderate-severe TBI. Those exposed to challenging environments showed reduced loss of brain matter, supporting the notion that "use it or lose it" applies to the chronic stages of recovery of the brain after TBI. Dr. Green states, "These findings, although preliminary, lay the foundation for the development of effective strategies that may dramatically improve long-term outcomes after injury."

This work was supported by the Canadian Institute of Health Research, Physicians Services Incorporated Foundation, the Natural Sciences and Engineering Research Council of Canada and the Ontario Neurotrauma Foundation. R. Green is a Tier 2 Canada Research Chair in Traumatic Brain Injury.

Environmental enrichment may protect against hippocampal atrophy in the chronic stages of traumatic brain injury. Miller LS, Colella B, Mikulis D, Maller J, Green RE. Frontiers in Human Neuroscience. 2013 September 24. [Pubmed abstract]