Membrane blebs and concussions

newsitem POSTMEDIA NEWS by Sharon Kirkey Monday June 4, 2012

“A Canadian doctor has found a way to detect concussions using a simple blood test that can tell within an hour after a head injury how severe the injury may be.”

“Earlier studies in rats found a number of proteins are released in the brain after traumatic brain injury.”

“The new study enrolled 295 people-96 of whom had a mild or moderate concussion. They were compared with two ‘control’ groups: normal adult volunteers without any injuries, and ‘non-head injured’ patients treated in emergency (departments) after a car crash or with broken bone, but no head trauma.”

“Some proteins studied earlier in brain injuries have been found in bones. (Linda Papa, a former Montrealer is an emergency physician and director of research for Orlando Regional Medical Center) According to Papa, ‘So if a patient has multiple trauma with a broken leg and head injury, we can’t tell if the protein is coming from the broken leg or the brain.’  ”

“Papa’s team found two proteins were higher only in the blood of patients with brain injury, detectable within  an hour after injury. Levels were higher in patients needing urgent surgery.”

So what proteins are being talked about here? What do they look like and what do they do? When you Google Papa and concussions and neurotrauma, you get a bunch of research articles which are cited among them,  αII spectrin break down products. Next question: what are spectrins? They are parts of cytoskeletal proteins that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal (5 sided-6 sided) arrangements, forming a scaffolding playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure.

The hexagonal arrangements are formed by tetramers of spectrin associating with short actin filaments at either end of the tetramer. These short actin filaments act as junctional complexes allowing the formation of the hexagonal mesh.

In certain types of brain injury such as diffuse axonal injury, spectrin is irreversibly cleaved by the proteolytic enzyme calpain,  destroying the cytosketelon. Spectrin cleavage causes the membrane to form blebs and ultimately to be degraded, usually leading to the death of the cell. Let’s look a little at what these proteins accomplish in Nature, let’s look first at invertebrates.

There are three spectrins in invertebrates,  α,β and βH. A mutation in β spectrin in the worm, C. Elegans results in an uncoordinated phenotype  in which the worms are paralysed and much shorter than wild-type. In addition to the morphological effects, the Unc-70 mutation also produce defective neurons. Neuron numbers are normal but neuronal outgrowth was defective.

Similarly, spectrin plays a role in fruit fly Drosophilia neurons. Knock-out of α or β spectrin in D. melanogaster results in neurons that are morphologically normal but have reduced neurotransmission at the neuromuscular junction  In animals, spectrin forms the meshwork that provides red blood cells their shape.

So notice the terms that are referenced here like: meshwork, morphological effects, outgrowth was defective, reduced neurotransmission at the neuromuscular junction, diffuse axonal injury and destroying the cytoskeleton.

Let me go back to one of the original quotes and emphasize a tensegrity spin on that earlier description, “Earlier studies in rats found a number of proteins are released in the brain after traumatic brain injury that appear to have affected the critical scaffolding supporting structure as parts of the cytoskeleton become delinked ”

Now I can’t put words into people’s mouths but as I have mentioned in previous essays, meshlink communication is all about how cells fashioned in tensegrity designed architectural shapes use and define their cellular configurations within shape altering interactions as deterministic cellular signalling. Shape shifts happen during protein interactions. If you severe the structure if you crush the mesh- the system will degrade in  its output. So to give a different orientation with to-days announcement about biomarkers,  concussion depending on its severity will have bits of the meshlink from diffuse axonal separation available as bits of the structure,  detectable in serum, or within   a  blood sample.

Back to some evidence for the role of spectrins. Within muscle, specfically in heart myocardial cells, αII spectrin distribution is coincident with Z-discs and the plasma membrane of myofibrils. Additionally, mice with an ankyrin (ankB) knock-out have disrupted calcium homeostasis in the myocardia. Affected mice have disrupted z-band and sarcomere morphology. In this experimental model ryanodine and IP3 receptors have abnormal distribution in cultured myocytes. The calcium signalling of the cultured cells is disrupted. In humans, a mutation within the AnkB gene results in the long QT syndrom and sudden death, strengthening the evidence for a role for the spectrin cytoskeleton in excitable tissue. (To ease the rapidity and timeliness of this essay I have sourced and used  from the Wikipedia definitions on spectrins to assist the descriptive concepts)

Also from previous essays I have used the terms the brain of the heart, based on shape sensing within its elements of motion coordination. So I beg to differ -it’s not just cardiac muscle or neurons or diffuse axonal injury or sarcomere morphology. It’s about the exquisite harmony of calcium signalling performed within dynamic shape sensing networks irregardless of their background neighborhood. Be it the heart or the brain, they work in unison at the nano level of signal ‘membrane integrity.’

So what is a concussion? It is a massive shape altering jarring cytoskeletal severance of multitudes of attachments depending on the zones of attachments within the mesh that connects everything together in the brain. It’s an infrastructure crash of the elements that are like a city shaken during a earthquake, parts of the structure detach. It’s those detached parts that Dr Papa is finding and calibrating with the damage.

I hope this different tensegrity view gives you an alternate window to look onto the ripples of a concussion affecting brain integrity following a concussion.


About cerebrovortex

Montreal Grandmother, Agnes Kent was saved by Raul Wallenberg from certain death, when he provided papers for her and her Mom to escape away from the Nazis. Today when asked what that escape meant, she replied,"Remind people, that while statesmen and whole countries remained silent and did nothing, a single individual chose to act, with ramifications that proved enormous. Similar choices confront us today. Write that simple truth she said, it can never be repeated often enough because the world keeps forgetting it."
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1 Response to Membrane blebs and concussions

  1. You are out doing yourself

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