Hyperreflexia, Memory, Neurological Disorders, Pain, Spasticity, Spinal Cord Injury, Writing

Top 5 Challenges in SCI Repair

Here are the top five challenges in the race for a cure for SCI:

  1. Post-injury survival – Keep nerve cells that survive the initial injury alive and healthy
  2. Regeneration and growth – Promote the re-growth of injured nerve cells and their fibers
  3. Axon pathfinding – Guide growing axons toward their normal targets (i.e., muscles or other neural tissues)
  4. Electrical conduction – Nerve cells must conduct electrical impulses with reliability and fidelity to carry information needed to execute complex tasks
  5. Synaptic connection –  Axons that reach their targets must connect and stabilize a line of communication

Progress: In my opinion, in more than 10 years in this field, I firmly believe that we’ve grown exponentially in terms of knowledge and application for milestones #1, 2,  3, and 4. And this is great news because this means that we are more than halfway toward fixing SCI. In fact, there are ongoing clinical trials in various parts of the globe investigating ways to increase the survival of nerve cells (a critical first step!), enhancing the growth of spared fibers, and guiding those axons toward their normal targets.

Next Steps: While less is known about how to promote re-connections between injured nerve cells and their targets (#5), we have a firm grasp on the molecular mechanisms involved in this challenge. We know that specific proteins interact in the growing nervous system (i.e., those that functioned when you were still in the womb, or just an infant) and that they turn-off, don’t work, or are non-existent in adulthood. So, in essence, we need to learn how to turn these switches back on, or replace them with functional ones. While no easy task, there are emerging tools to do this, including genetic therapies which has become a huge advancement and addition to our repair tool box.

What I expect: In the next few years, we will see some very big pushes on various research fronts in the SCI battle space. I think the biggest successes and those soonest to arrive will be in the form of new strategies designed to overcome many of the serious quality-of-life issues associated with SCI, including pain, reflex disorders, and poor autonomic function. Hang on; stay alert; stay hopeful!

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Academia, Hyperreflexia, Memory, Missions, Neurological Disorders, Pain, Problems to Solve, Spasticity, Spinal Cord Injury, Writing

Spinal cord memory: a next step forward?

I study spinal cord injury (SCI). It’s been a journey I’ve taken for myself these past many years, 8 or so. There are some ideas that don’t leave you; they get stuck up there in the dark crevices, like a bit of juice in a city gutter. It’s a mix of all stuff you’ve read, heard, or thought about.

Here I am. I need to start somewhere with this. But, this has been on my mind for 2-3 years…. trying to flesh it out.

The brain is a computer.

As a computer, the brain has the biological mechanisms for storing information. We call this memory. The idea that the brain is a memory machine is old, ancient, really. It’s part of our everyday understanding of what the brain does. It takes information, processes it, then stores it for recollection (remembering) later.

Now, what most people don’t know is that the spinal cord also “remembers”. The spinal cord also contains the same machinery that the brain has when it comes to forming and storing information (i.e., memories).

I’ve been exploring the idea that memory can go wrong.

‘Memory is linked to pain’ is well understood, if you think about it. Do you remember what it’s like to get a paper-cut? More interesting, do you remember what it’s like to be betrayed by a friend, or feel guilty, forms of emotional pain?

Inside the spinal cord are memory systems. Injury or disease, like SCI, can disrupt these systems, putting them into a kind of over-drive. The neurons no longer process and output electrical information normally. Turn on the radio, you hear music. Switch to a channel that has no information, or poorly received information, and you get static. That’s what we call neuropathic pain in the most basic sense: the absence of good information and amplify whatever noise is left.

Maybe, the same thing is happening there in the motor system, the machine parts that control movement. While some people with SCI don’t feel any ability to move, they are weak or even paralyzed; there are other individuals with SCI that have too much movement. Their muscles do not react voluntarily, moving or twitching on their own (some may call this “dystonia” or “myoclonus”). The intensity of these muscle contractions, or twitchings, could be of such great intensity that it’s actually painful or uncomfortable. There’s no relaxation posture or state of the muscle; it’s constantly active.

Here’s what I think is going wrong. Like the analogy I used for neuropathic pain (see above), the electrical activity in the neurons that control muscles is abnormally activated. They are over-excitable, as we like to say in the field.

Why are they over-excitable, which causes them to make muscles contract involuntarily, even painfully?

So many reasons. No laundry lists here. Here’s my take on it the problem….

The body is alive. It is constantly healing itself against insults the world throws at it. Your skin regenerates automatically when you cut yourself. When you break a bone, the doctor doesn’t “heal” you, your body does. All the doctor does is make sure your bones heal themselves, correctly.

I tell you this so you know that the spinal cord does heal itself. We call this spontaneous regeneration. This happens all the time after SCI. For example, after the initial injury, a patient (or in my case, a rodent) undergoes a period of dramatically lost function, also known as spinal shockThis can be painful, uncomfortable (I’m using really weak adjectives, forgive me).

Overtime, however, the subject regains some function. This is due to two major things happening, we mostly think. First, balances of chemicals and electrical properties of the nervous system slowly return to a state where things that aren’t cut-off can function (albiet not 100%) and transmit information again. Second, those neuron that do survive and not directly injured by the SCI have an internal ability to spontaneously grow. Some types of cells are more capable than others, and certain chemicals need to be available, but generally, all neurons in the spinal cord have some capability, even in the adult, to grow or spontaneously regenerate.

Spontaneous regeneration, also known as reactive neuronal plasticity, appears to be a good thing. 

And it is. It’s the body’s self-healing process. But sometimes, it can go wrong. In my studies, I examine how the internal capability of neurons to spontaneously form new connections and regrow can lead to serious disorders after SCI. Using a broad brush explanation, for example, if a pain cell receives too many connections from the wrong place, then excess pain can be a result. The same is true for muscle function. If a cell receives too much information from a spontaneously regenerated nerve, then we might expect those muscles to have too much stimulation.

What bursts my mind is that this all happens internally, deep in the bowels of the spinal cord. Unlike a broken bone, in which a doctor can intervene by making a cast to hold the broken parts close together, allowing them to regenerate and heal back into the normal, original shape, we can’t do that with the broken spinal cord. Not yet.

It’s a musical orchestra in there….

There are many circuits that are impacted by SCI. We, as the research field, are struggling to dissect what wires go where. Let’s say…I take my laptop and throw it on the floor. It doesn’t break, not entirely, but the keyboard doesn’t work anymore. How do I know how to fix it, if I don’t know where all the wires are supposed to go?

I’m now looking at how my studies in neuropathic (nerve) pain are similar to what goes wrong in the motor system that leads to really annoying, painful, or uncomfortable problems. Many bodily systems require a huge orchestra of neurons working in concert with each other. I’m basically taking apart the orchestra, starting with the flute section.

Yes. Let’s play on.

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