Blocking Newly Identified Molecule May Improve And Speed Recovery From Stroke

Blocking Newly Identified Molecule May Improve And Speed Recovery From Stroke

Researchers at UCLA have identified a novel molecule in the brain that, after stroke, blocks the formation of new connections between neurons. As a result, it limits the brain's recovery. In a mouse model, the researchers showed that blocking this molecule - called ephrin-A5 - induces axonal sprouting, that is, the growth of new connections between the brain's neurons, or cells, and as a result promotes functional recovery.

If duplicated in humans, the identification of this molecule could pave the way for a more rapid recovery from stroke and may allow a synergy with existing treatments, such as physical therapy.

Stroke is the leading cause of adult disability because of the brain's limited capacity for repair. An important process in recovery after stroke may be in the formation of new connections, termed axonal sprouting. The adult brain inhibits axonal sprouting and the formation of these connections. In previous work the researchers found, paradoxically, that the brain sends mixed signals after a stroke - activating molecules that both stimulate and inhibit axonal sprouting. In this present work, the researchers have identified the effect of one molecule that inhibits axonal sprouting and determined the new connections in the brain that are necessary to form for recovery.

The researchers also developed a new tissue bioengineering approach for delivering drugs to the brain after stroke. This approach uses a biopolymer hydrogel, or a gel of naturally occurring brain proteins, to release neural repair molecules directly to the target region for recovery in stroke - the tissue adjacent to the center of the stroke.

Last, the paper also shows that the more behavioral activity after stroke, such as the amount an impaired limb is used, the more new connections are directly stimulated to form in the injured brain. This direct link between movement patterns, like those that occur in neurorehabilitation, and the formation of new brain connections, provides a biological mechanism for the effects of some forms of physical therapy after stroke.

Iron Bracelets - Do They Work?

Recently we came across this question and decided it would be best to post some more information regarding this. This is what we were asked.

Q.

I recently came across a new kind of sports enhancement bracelet. Apparently it emits positive ions that are good for you. The bracelet is also a watch. There are credible scientific studies on positive ion therapy and apparently positive ions are good for you. They are used to treat seasonal affective disorder (although the result of the study does go on to cast doubt about its findings).

The question is whether it is possible for positive ions to affect your good health and if so whether a bracelet can deliver enough positive ions to have any effect at all. It would also be beneficial if you have any links to medical studies on these devices.

So here is the answer we provided with a little more information.

A.

Related questions: Do those hologram bracelets do anything at all? and also Has electromagnetic therapy been proven effective?

The only FDA approved study that has any claims for the benefits of ions is for the use of air filters. Any other claims are beyond the scope of any studies, and rely on the gullibility of customers. The fact that "Lithium Ion" batteries exist may add confusion for the consumers, but is a totally different thing. There are no credible studies on these bracelets, so you will not find any links backing up their claims. And see the bolded quote below. The Web MD article that the company used as a "reference" again refers to machines that actually expend electricity to generate negative ions in the air. And as the article itself sates, in relation to relieving depression, or having added benefits against allergies:

It's too early to tell for sure

But again, keep in mind that machines are required for this process, not a plastic bracelet with a hologram on it.

This is an excellent opportunity to practise grass roots scepticism. Ask yourself: By what mechanism is this supposed to work? How does the proposed mechanism align with what we know about science, biology, physics, etc.? Also, you may be interested to know that in some countries, Power Balance must state that they have no actual scientific backing for their claims. The Placebo band is just as effective, and much cheaper.

What sort of demo was done at the expo? Was it Applied Kinesiology by any chance? That is a well known bit of deliberate deception.

A quote from the first link:

Power Balance bracelets promise to improve balance, strength and flexibility and feature some lofty endorsers: Shaquille O’Neal, Drew Bree's and Nicole Branagh, an Olympian from the University of Minnesota. Yet the maker of the $30 bracelets admitted this week that there’s no scientific evidence that the things actually work.

The producers of Power Balance bracelets have sold them by the millions around the globe. They adorn the celebrity wrists of Robert de Niro and Kate Middleton, among others. The hologram-embedded rubbery bracelets “work with your body’s natural energy field” in ways similar to “concepts behind many Eastern philosophies,” the Power Balance website explains.

These claims got the attention of the Australian Competition and Consumer Commission, which compelled Power Balance to issue a letter that was published in various media outlets Down Under.

“We admit that there is no credible scientific evidence that supports our claims,” the company wrote. “Therefore we engaged in misleading conduct.”

Also, while not a strict debunking of the exact device you link to, I found this interesting write up at JREF. I think the quackwatch link may provide you with additional information.

How to Debunk Biomagnet Therapy in Less Than a Minute

Written by Brandon Peterson
Wednesday, 17 March 2010 10:32

I recently had the opportunity to attend The Amaz!ng Adventure 5. While at Grand Turks, our final port, I was wandering through the duty-free shop looking for deals on liquor (Jack Daniel’s Single Barrel for $39!) when I happened upon a tableful of woo. Seeing as I was a medical student on a skeptical cruise, I had to stop and have my wife help make this video.

In my off-the-cuff video, I didn’t have the opportunity to mention the lack of scientific evidence for their claims. Even if the magnetic field did penetrate the skin, it still would not stimulate blood flow because the amount of iron in blood is far too small. If blood did have a strong magnetic attraction, your body would explode in an MRI (which would be cool, I admit).

I also didn’t have time to discuss the clinical trials that have been performed to evaluate efficacy. As usual with CAM research, earlier poor quality studies were weakly positive (1,2), while more recent high quality studies and meta-analyses are definitively negative (3,4,5).

I also forgot to mention the numerous court rulings in the late ‘90s and early ‘00s against companies making false claims about these products. This issue is discussed extensively on Quackwatch for those interested (6). In a nutshell, companies that fraudulently claimed to treat specific illnesses (arthritis, diabetic neuropathy, migraines, etc.) were sued. Now, they use nebulous phrases such as “support the healing process” or “restore natural energy.” You know, phrases that have not been evaluated by the Federal Drug Administration and are not designed to diagnose, treat or blah blah blah.

In short, magnet therapy is a great case study of CAM. The lack of scientific plausibility, the progression of the medical literature, and the FDA Miranda Rights statement are all characteristic of CAM. And if a lowly medical student can debunk it is less than a minute, how good can it really be?

1. Harlow T, Greaves C, White A, et al. Randomised controlled trial of magnetic bracelets for relieving pain in osteoarthritis of the hip and knee. BMJ 2004; 329:1450-1454

2. Vallbona C, Hazelwood CF, Jurida G. Response of pain to static magnetic fields in postpolio patients: A double-blind pilot study. Archives of Physical and Rehabilitative Medicine 1997; 78:1200-1203.

3. Winemiller MH and others. Effect of magnetic vs sham-magnetic insoles on plantar heel pain: a randomized controlled trial. JAMA2003; 290:1474-1478.

4. Pittler MH. Static magnets for reducing pain: systematic review and meta-analysis of randomized trials. CMAJ 2007; 177(7): 736-42.

5. Cepeda MS, Carr DB, Sarquis T, et al. Static magnetic therapy does not decrease pain or opioid requirements: a randomized double blind trial. Anesth Analg 2007; 104. 290-294.

6. Barrett S. Magnet therapy: a skeptical view. Accessed March 15, 2010. Available at http://www.quackwatch.org/04ConsumerEducation/QA/magnet.html

I will note that there are things that electromagnetic fields can do to the human body. In particular the neural effects if placed about the head (see God Helmet). However, the main thing to do when dealing with claims like this is to ask yourself: By what mechanism is this device claiming to work? How does this align with what we know about biology, chemistry, physics, etc.? Does the claimant use language that would be high on the crankpot index?

If you are starting to see a trend here, that is because there is one. There is no known mechanism for these things to work, and their claims are well beyond what the science would indicate.

Biomechanics of joint manipulation

Manipulation can be distinguished from other manual therapy interventions such as joint mobilisation by its bio mechanics, both kinetics and kinematics.

Kinetics

Until recently, force-time histories measured during spinal manipulation were described as consisting of three distinct phases: the preload (or prethrust) phase, the thrust phase, and the resolution phase. Evans and Breen added a fourth ‘orientation’ phase to describe the period during which the patient is oriented into the appropriate position in preparation for the prethrust phase.

When individual peripheral synovial joints are manipulated, the distinct force-time phases that occur during spinal manipulation are not as evident. In particular, the rapid rate of change of force that occurs during the thrust phase when spinal joints are manipulated is not always necessary. Most studies to have measured forces used to manipulate peripheral joints, such as the metacarpophalangeal (MCP) joints, show no more than gradually increasing load. This is probably because there are many more tissues restraining a spinal motion segment than an independent MCP joint.

Kinematics

The kinematics of a complete spinal motion segment when one of its constituent spinal joints are manipulated are much more complex than the kinematics that occur during manipulation of an independent peripheral synovial joint. Even so, the motion that occurs between the articular surfaces of any individual synovial joint during manipulation should be very similar and is described below.

Early models describing the kinematics of an individual target joint during the various phases of manipulation (notably Sandoz 1976) were based on studies that investigated joint cracking in MCP joints. The cracking was elicited by pulling the proximal phalanx away from the metacarpal bone (to separate, or 'gap' the articular surfaces of the MCP joint) with gradually increasing force until a sharp resistance, caused by the cohesive properties of synovial fluid, was met and then broken. These studies were therefore never designed to form models of therapeutic manipulation, and the models formed were erroneous in that they described the target joint as being configured at the end range of a rotation movement, during the orientation phase. The model then predicted that this end range position was maintained during the prethrust phase until the thrust phase where it was moved beyond the 'physiologic barrier' created by synovial fluid resistance; conveniently within the limits of anatomical integrity provided by restraining tissues such as the joint capsule and ligaments. This model still dominates the literature. However, after re-examining the original studies on which the kinematic models of joint manipulation were based, Evans and Breen[2] argued that the optimal prethrust position is actually the equivalent of the neutral zone of the individual joint, which is the motion region of the joint where the passive osteoligamentous stability mechanisms exert little or no influence. This new model predicted that the physiologic barrier is only confronted when the articular surfaces of the joint are separated (gapped, rather than the rolling or sliding that usually occurs during physiological motion), and that it is more mechanically efficient to do this when the joint is near to its neutral configuration.

Cracking joints

Main article: Cracking joints

Joint manipulation is characteristically associated with the production of an audible 'clicking' or 'popping' sound. This sound is believed to be the result of a phenomenon known as cavitation occurring within the synovial fluid of the joint. When a manipulation is performed, the applied force separates the articular surfaces of a fully encapsulated synovial joint. This deforms the joint capsule and intra-articular tissues, which in turn creates a reduction in pressure within the joint cavity. In this low pressure environment, some of the gases that are dissolved in the synovial fluid (which are naturally found in all bodily fluids) leave solution creating a bubble or cavity, which rapidly collapses upon itself, resulting in a 'clicking' sound. The contents of this gas bubble are thought to be mainly carbon dioxide. The effects of this process will remain for a period of time termed the 'refractory period', which can range from a few minutes to more than an hour, while it is slowly reabsorbed back into the synovial fluid. There is some evidence that ligament laxity around the target joint is associated with an increased probability of cavitation.

Clinical effects and mechanisms of action

The clinical effects of joint manipulation have been shown to include:

▪   Temporary relief of musculoskeletal pain.

▪   Shortened time to recover from acute back sprains (Rand).

▪   Temporary increase in passive range of motion (ROM).

▪   Physiological effects upon the central nervous system.

▪   No alteration of the position of the sacroiliac joint.

Common side effects of spinal manipulative therapy (SMT) are characterised as mild to moderate and may include: local discomfort, headache, tiredness, or radiating discomfort.

Shekelle (1994) summarised the published theories for mechanism(s) of action for how joint manipulation may exert its clinical effects as the following:

▪   Release of entrapped synovial folds or plica

▪   Relaxation of hypertonic muscle

▪   Disruption of articular or particular adhesion

Unbuckling of motion segments that have undergone disproportionate displacement