The curious case of applying electric shock to treat brain injuries

Author: Hamideh Emrani, 04/04/17

The month of March is a time for celebrating women around the world. As a science enthusiast, I have been so inspired by the women I see succeeding in the research field. Since I started writing for this blog, I have had the chance to write about and interview female researchers such as Jin Hyung Lee of Stanford University, and Milica Radisic and Molly Shoichet of Univerisity of Toronto (U of T).

I recently had a friendly chat with Dr. Cindi Morshead, also with U of T. I know about her research from my years in graduate school. But also, I received great advice from her when I was at a tipping point in my life. So, when I saw the news that she had received a Connaught Innovation Award from U of T, I made plans to meet her and talk more about her research.

Dr. Morshead received her PhD at U of T, and became a faculty member in the department of surgery in 2003. Currently, she is the Chair of the Division of Anatomy, Department of Surgery, and has appointments at the Donnelly Centre for Cellular & Biomolecular Research (CCBR), Institute of Biomaterials & Biomedical Engineering, Institute of Medical Science and the Graduate Department of Rehabilitation Science. Her main area of expertise is in stem cell biology and adult neural stem cells. Her lab focuses on studies exploring fundamental questions and the different applications neural stem cells can have in disease settings such as stroke, spinal cord injury, cerebral palsy and acquired brain injury.

Can you tell us a bit more about your lab projects and the research you are interested in?

My lab mostly focuses on stem cells and animal disease modeling. We try to take what we learn in the dish at the lab bench and apply it in vivo.

We also do some electric field work, which is the project we were awarded the Connaught Award for. We have an excellent collaboration with Dr. Milos Popovic on this project. That’s more of an engineering type strategy in that we are trying to apply what we learned about the effect of electrical stimulation on stem cells in a culture dish and how it can be applied for endogenous repair inside the brain.

With the idea of endogenous repair as a focus, we also have projects that study the effects of drugs for cognitive and motor recovery in models of disease such as cerebral palsy and acquired brain injury. Interestingly, we have shown that the stem cell niche plays a really important role in how these cells behave when subjected to different drugs. Even the same drug and the same dose can have differential effects on the behavior of the progenitor cells based on what region they come from, be it the spinal cord or the brain, and male or female.

Can you explain more about the project you received the Connaught Innovation Award for?

It is well established that electric fields are found everywhere in the body and are important for different processes throughout the life cycle. For instance, electric fields are important for human development and disrupting this process can impede proper cell and organ maturation, likely due to alterations in cell migration. After development, electric fields have been shown to be important for wound healing by enabling regenerating cells to migrate towards the site of injury. The electric fields that are generated have been shown to have an impact on the migration of cells towards the injury site, which happens during wound healing. If those fields are somehow disrupted, you won’t see any cellular migration and the wound will not heal.

With these initial observations in mind, our group tested whether electrical fields can have an effect on neural precursor cells, (NPCs: cells that can generate neural lineage of our nervous system.) These cells are inherently migratory. When there is an injury happening inside the brain, such as stroke, they migrate to the injury site. However, their migration is not as robust as needed. We evaluated the possibility of using electric fields in generating directed migration of NPCs. We were able to show that the cells migrated quite robustly towards a cathode (positive electric charge end) when cultured in a dish.

Next we studied whether this occurred in other cell types, including differentiated neural cells as well as skin stem cells. There was no effect on migration in response to electric current in these other cell populations, indicating that not all related cell types respond similarly to the electric field and this appears to be specific to NPCs. When exploring the potential mechanism of action for this NPC specific migration, we found that one important factor was calcium signaling, which is the influx and outflux of calcium ions to the cell. The cells will no longer migrate in the absence of calcium signaling.

Therefore, in designing stem cell-based therapies to repair the injured brain, the application of electric fields seemed like a potential therapeutic approach, specifically targeting the movement of NPCs to the site of brain injury. We are now doing the work in vivo with the Connaught Innovation Award funding.

What does biphasic electrical stimulation mean?

The term biphasic electrical stimulation means that the cells are subject to pulses of electrical stimulation in positive and negative phases. This is more clinically relevant than the previously used direct current electric field applications in in vitro studies.

Currently, we are transplanting neural precursor cells into the brain and applying this biphasic electric field to try and get these cells to migrate in vivo. We are still working on optimizing the parameters in vivo.

Which projects are you more passionate about and which one seems the most challenging?

I really like all of the projects and, in general, my most favorite thing about all these is the fundamental biology of the cells. We try to learn about the cells in the dish and then apply it to models of injury, which I think is the most exciting part of what we can do with that knowledge.

And regarding the challenges, I think all animal models also have challenges. For instance, the experiments are labor intensive and it is important to use models that mimic the disease or injury you are trying to treat. This is particularly important for preclinical work relating to stroke, cerebral palsy and spinal cord injury, to name a few. Using the example of the animal studies with electric fields, there are numerous steps involved in the biphasic electrical field stimulation project. And there are multiple factors to take into consideration. As an example, putting an electrode into the brain will cause an injury on its own and generate an electric field. Control experiments will be critical for interpreting the findings of our studies.

We recognized International Women’s Day last month.  As a woman in science and a leader in your field, do you have any advice for female students interested in a career in academia?

I think the biggest challenge for women in science does not relate to their ability to do the science and ask the right questions. The biggest challenge is being able to balance their career and family life. By the time women finish their graduate education, many are ready to start a family and we cannot ignore that it falls on them to decide whether to take time off and take care of their kids or to keep going and postpone having a family.

My main advice is do not despair; it is doable. However, keep in mind that you definitely need to be able to prioritize. For instance, I said to myself that I was never going to miss an event for my kids. I am not missing a concert, I am not traveling during their graduation. I just made that a priority, which incidentally took a lot of stress off for me.

I vividly remember that when my kids were small, my husband and I arranged our schedules in a way that I would take care of the kids in the morning and go to the lab a bit later so that he could start work before 7 am. Then, we would both be home with the kids in the afternoon, and I would go back to the lab after I put the kids to sleep. This meant that we had to be really organized and we had to live close to the lab.

Also, having a support system is necessary too. I was able to arrange things with my husband, and my family also lived close by. But without that it would be really challenging. For many it is not like that, and a lot of women have to put having kids on hold. There is never a “perfect” time to have kids if you are planning next steps in your career. You have to find a balance that works for you and you just have to make it work. I also think it is really important to have a backup plan. There are many ways to be scientifically involved and make money other than being an academic.

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Hamideh Emrani

Hamideh Emrani

Hamideh is a scientific communicator and the founder of Emrani Communications, serving clients in Toronto (University of Toronto) and California (Stanford University). She earned her B.Sc. in Cell and Molecular Biology at UC Berkeley and finished her M.Sc. at the University of Toronto (U of T). She was an intern at the Carnegie Institute at Stanford University, honours research student at UC Berkeley and has won awards for best podium and best poster presentations at the Faculty of Dentistry and IBBME at U of T. She is passionate about science and loves to talk and write about it. You can follow Hamideh on Twitter at @HamidehEmrani.
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