Monday, January 28, 2013

What do Dead Bodies, Nematodes, and a former Oregon State Beavers Pitcher Have in Common?


by Ellen Mintz

          Believe it or not, these three seemingly unrelated organisms have each undergone a process that is incredibly significant in medical history and current scientific research.  To really answer that question though, we need to take a closer look at the most significant and important organ in our body: the brain.
           The brain, along with the spinal cord, comprises the central nervous system. As its name implies, this is the command center of all of the activity that keeps our bodies alive, aware, and functioning.  The brain controls crucial processes like breathing, digesting, and waking up in the morning. Stimuli from the environment around us send messages through our bodies in the form of electrical signals.  Neurons are the cells that transmit these signals, communicating from cell to cell through the release of tiny chemicals called neurotransmitters.  Upon reaching the central nervous system, these signals are processed and delivered as electrical impulses to effectors such as skeletal muscle and digestive organs.
  
            In addition to movement, the brain controls emotions and feelings.  These arise from increased activity in different parts of the brain (check out the map below!).  Regions including the amygdala, frontal cortex, hypothalamus, and cerebral cortex can all lead to feelings of sadness and depression.

Brain Anatomy
            Many tissues around the body such as the skin, are quick to repair themselves following damage from injury or the natural process of aging through the use of unspecialized stem cells that then differentiate into the needed cell type.  The central nervous system, however, is notoriously difficult to repair and was believed to have no source of stem cells. In 1998, scientists discovered cells in the hippocampus that were able to become new neurons, and subsequent discoveries of more of these cells led to the hope that conditions such as paralysis that are often the result of traumatic brain injury could be treated.  This has of yet not been proven to be completely successful.

Fluorescence image of a neural stem cell
            It has taken centuries to accumulate all of the knowledge that we have today about the brain.  Starting in the late 1700s and into 1800s, research in neurobiology and of the electrical impulses in the nervous system made huge strides.  It was during this time that scientists discovered that muscles and nerves were excited by electrical signals.  This revelation was demonstrated by applying electric currents to the bodies of cadavers (dead bodies, anyone?!), resulting in macabre post-death movements sure to excite any pre-movie era horror enthusiasts. Eventually, this led to the discovery by Italian scientist Luigi Rolando in 1809 that the brain responded to electrical pulses also.

            It took another 50 years for scientists to develop the knowledge and instruments to be able to apply this knowledge of the electrical conduction of the central nervous system directly to the organs themselves, and use electricity to control different levels stimulation as a method for investigating brain function.  First in animals like dogs and monkeys, and much later in humans, electrical stimulation of the brain provided knowledge the physiology of this organ.  When this was then applied to the treatment of different disease conditions, particularly mental illness, the fun really began!

What ECT actually looks like!
            One of the first methods of electrical brain stimulation to treat depression and personality and mood disorders was electroshock therapy, now called electroconvulsive therapy, or ECT. The idea behind electroconvulsive therapy is to cause a huge storm of electrical activity in different parts of the brain.  This invokes a small seizure in the patient and resets electrical pathways and brain chemistry.  While often seen fictionalized in popular media as a painful, bone jarring and maniacal spasms, it is in reality done under anesthesia and can be successful when other treatments have failed.
NOT an accurate representation of ECT!

            In 1985, a procedure called transcranial magnetic stimulation, or TMS, was introduced as a less invasive and intense method of mood adjustment and depression treatment and approved for use on humans in 2009. This technique involves placing electromagnetic coils near the skull to deliver quick magnetic pulses to the brain, increasing the firing of neurons in mood associated brain regions.  There is a decrease in the risk of inducing a seizure using this procedure, making it safer and applicable to a wider range of patients than traditional ECT.
            
C. elegans
        Taking the idea of magnetic stimulation multiple steps further, a physicist at SUNY Buffalo, Dr. Arnd Pralle, utilized magnetic fields to heat up nanoparticles placed in neurons in the brain.  These particles activate temperature sensitive ion channels in the cells, causing them to react and potentially stimulate positive changes in neuron firing patterns. Although this method has yet to be tested in human brains, it has been shown to cause Caenorhabditis elegans, a nematode used as a model organism in developmental biology and neurology (a test subject like the dead bodies of earlier…), to change what direction they were moving in. Dr. Pralle and his collaborators are currently investigating using genes from bacteria that are known to make magnetic nanoparticles and integrating them into humans using a viral therapy, in addition to other biocompatible delivery methods.  Ultimately, this technique would be able to elucidate neuronal circuits in the brain by allowing stimulation of different regions controlling mood and behavior, and could be used as a research tool to study conditions such Parkinson’s disease and traumatic brain injury that resulted from dysfunctional or impaired neurons.

            The spinal cord has also been subjected to electrical stimulation as well, however not for the same purposes as the brain.  Electrical stimulation of the spinal cord has been investigated as a way to improve limb function and health, focusing on patients with spinal cords or body parts that have been damaged by accidents or debilitating diseases.  Because the spinal cord transmits electrical signals and impulses from the brain and reflex neurons to muscles and organs around the body, damage can result in loss of movement and control, lack of sensation to stimuli including pain, temperature and touch, and reduced to nonexistent function in crucial organs and systems including the heart, lungs, digestive, and reproductive systems.  It has been shown however that rats with implanted electrodes in their spinal cord regain minor leg function when placed on a treadmill, and eventually are able to walk on their own.  Brief periods of epidural spinal cord electrical stimulation was shown to relieve pain, result in skin ulcer healing, and increase circulation in patients suffering from limb-threatening ischemia.

            Still curious about how baseball fits into this topic? In 2006, Rob Summers, a pitcher for Oregon State, was paralyzed from the neck down in a tragic hit and run accident, ending his baseball career.  Intense rehabilitation and therapy improved his upper body movement and he eventually regained the use of his arms.  In 2009, he sought out the help of Dr. V. Reggie Edgerton, a professor and neurobiologist at UCLA who had previously led spinal cord studies on electrical stimulation in rats.  Dr. Edgerton and his collaborators implanted electrodes in the lower sections of Summers’ spinal cord and through electrical stimulation, were able to temporarily reactive the neural networks in his spinal cord.  Summers was able to move his legs while on a treadmill with upper body support, briefly stand on his own, and also experienced huge improvements in blood pressure, bladder and sexual function, and temperature regulation. 

            All of these therapies involving electromagnetic activity and the central nervous system to treat depression and other diseases and pathologies have many benefits and are good starting points for the development of safer and less invasive procedures.  Further applications of these concepts could provide longer, healthier, and happier outlooks to those suffering from paralysis, depression, and neural diseases like Parkinson’s.  In structures as multifaceted and complex as the brain and spinal cord, it is anyone’s best guess as to from where the next discovery will come!
           
References
Berg, Nate. "Spine Stimulator Lets the Paralyzed Stand Again." Discover. Jan 2013: 36. Print.

Clemmons, Anna Katherine. "Rob Summers Willing to Walk Again." ESPN.com. 24 Dec 2011: Web. 28 Jan. 2013. <http://espn.go.com/espn/otl/story/_/id/7373090/rob-summers-former-oregon-state-beavers-pitcher-paralyzed-accident-never-imagined-impact-world-baseball>.

"Electroconvulsive Therapy." Mayo Clinic. Web. 29 Jan 2013. <http://www.mayoclinic.com/health/electroconvulsive-therapy/MY00129>.
Freedman, David. "The Happiness App." Discover. Jan 2013: 10-11. Print.

Harkema, Susan, Yury Gerasimenko, V.R. Edgerton, et al. 2011. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. 377. 1938-47.

Hsu, Charlotte. "Effort to Remotely Control Brain Cells Gets Push from Innovative Grant." News Center. State University of New York at Buffalo, 16 Apr 2012. Web. 28 Jan 2013. <http://www.buffalo.edu/news/releases/2012/04/13359.html>.
Jacobs, Michael J.H.M., Paul Jornig, Roeland Beckers, et al. 1990. Foot salvage and Improvement of microvascular blood flow as a result of epidural spinal cord electrical stimulation. Journal of Vascular Surgery. 12.3: 354-60.

"NINDS Deep Brain Stimulation for Parkinson's Disease Information Page." Disorders A-Z. National Institute of Neurological Disorders and Stroke, 07 Feb 2012. Web. 28 Jan 2013. <http://www.ninds.nih.gov/disorders/deep_brain_stimulation/deep_brain_stimulation.htm>.

"Primary Damage." Spinal Cord Injury. Macalester College Department of Psychology. Web. 28 Jan 2013. <http://www.macalester.edu/academics/psychology/whathap/ubnrp/spinalcord05/primarydamage.html>.

Sabbatini, Renato M.E.. "The History of Electrical Stimulation of the Brain." Web. 29 Jan 2013. <http://www.cerebromente.org.br/n18/history/stimulation_i.htm>.

Image References

http://www.news.wisc.edu/newsphotos/images/Zhang_neural_stem_cells04.jpg

http://img2.timeinc.net/health/images/journeys/depression/woman-electroconvulsive-therapy-200.jpg\ http://leightonwinkler.files.wordpress.com/2012/07/aversion-therapy-clockwork-orange.jpg


http://www.apparelyzed.com/_images/content/spine/spinenerves.jpg


3 comments:

  1. That pitchers story is really sad but inspirational. I imagine those electrodes that were implanted in him jump starting his spinal cord nerves like a car battery. I'm not sure how correct that analogy is but this is really awesome stuff!

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  2. I was wondering how long it usually takes to see effects using electrical stimulation in the spinal cord versus the brain, but it could just be situational. Awesome review, I learned a lot!

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  3. I love your blog title! Very interesting stuff. Does the electrical stimulation actually induce the stem cells to become new neurons? Or is the stimulation simply helping already existing neurons to fire?

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