Tag Archives: science

The Role of Neuroplasticity in Constraint-Induced Therapy

WOOHOO! I am finally done with my senior paper. As you may surmise from the title I chose to write it on the neuro-mechanics involved with CI therapy. It’s written with a more informal tone but nonetheless it still landed me high marks.  Comments, questions, and retweets (#revfrost) are always welcome. Enjoy!

ABSTRACT: The human brain is capable of extraordinary change. The impact of strokes can be devastating and often times seen as refractory. Constraint Induced (CI) therapy has proved beneficial in alleviating common symptoms caused by strokes. Recent evidence provides an insight in identifying the biological mechanisms exploited by CI-therapy: neurogenesis, gliosis, and synaptogenesis.

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A Brief History of the Brain: Ancient Egyptians

The brain has always been looked upon with reverence and awe for its power and capacity of conscious thought… right? Absolutely not. Not only is the brain the coolest thing in science (no bias, I swear) but historically it has been neglected or set aside as the “housing of the soul.” Well, that’s irritating.

So let’s start back in ye’ olden days of the pharaohs. It seems the Egyptians fall into a weird category of belief. They recognized the problems that would arise from head wounds but ignored it in terms of thought and consciousness. During the mummification process they would enter the nasal cavity, break through the thin-layered ethmoid bone, and draw out the contents of the skull. We’ve all heard this spiel since elementary school. The important parts to ask though are the why and how.

The why seems relatively straight forward. It was removed along with all the other organs excluding the heart to prepare the dead for their afterlife. The heart was left in place to be judged in Duat, the Egyptian underworld. Under supervision of Anubis, the heart was weighed against Ma’at’s feather of truth. The Declaration of Innocence: Spell 125 details a 42-part moral system which they were judged upon – similar to that of the 10 Commandments of Christianity but 2000 years prior (coincidence? >_>). If the heart was found to be unworthy it was eaten by the “devourer”, Ammut. If not, they proceeded to Aaru, the heavenly reed field.

That’s neat and all, but it’s not the whole story. Only 50% of recovered mummy skulls had the brain removed prior to mummification. In addition, the eyes had also been removed and replaced with various materials. Why? Because they rot and stay moist. The whole point of mummification is to remove as much water as possible to preserve the remaining tissue. The body needed to stay as recognizable as possible; I’ll explain in a minute. An example concoction used as a dehydrant consisted of 84.7% sodium carbonate or bicarbonate, 1.5% sodium chloride, and 13.8% sodium sulphate. While this prevents most bacterial decay it doesn’t stop it all. The brain and eyes start to leak fluid and rot. Quick fix? Take them out. Sure, it’s a little more difficult than the other organs, but it works better in the long-run. A dry mummy is a happy mummy.Credit goes to http://www.offbeatenough.com/

Another key part is how the brain was removed. Mummification was usually performed in a manner that minimized cosmetic damage as it was believe the soul (the Ba) needed to recognize the body to return to it every night. The  common belief of the process behind it seems to be a gross misconception. It is largely held that the brain was sucked out, scooped out with a hook or some variation thereof. For the most part, this is untrue. The tool used did indeed have a hook but it did not function in that fashion. The viscosity of the brain allowed it to stick to the entire tool. So, as the tool would be drawn out it would bring brain with it. With repeated entry from the tool the inside tissue would begin to liquefy and eventually could be poured out of the nasal cavity.

The Egyptians were pioneers of the medical realm. They were even recognized by Homer in the Odyssey: “In Egypt, the men are more skilled in medicine than any of human kind.” The Edwin Smith Surgical Papyrus details a great many of their accomplishments along with a few of their more… unique practices. Maybe with a bit more time they could have perfected the art of medicine a little more. Until next time, remember to “pour milk into both ears” for a wounded temple.

The Problem of Brain Removal during Embalming by the Ancient Egyptians
F. Filce Leek. The Journal of Egyptian Archaeology

Dynamic Neuroplasticity after Human Prefrontal Cortex Damage.

ResearchBlogging.org In this article, the authors focused on the effects of a unilateral lesion within the prefrontal cortex. Human vision works upon a rather backwards system. Information from the left side of each eye moves toward the left occipital lobe to be analyzed. The right follows an identical pattern.

So essentially, two sides of the eyeball swap information between hemispheres. From here, the information is sent forward along the current hemisphere to be analyzed by the prefrontal cortex (PFC).Because what else would you expect from the brain? In a nutshell, the left and right fields of vision (of a single eye) are interpreted by different halves of the brain. This is where the problems begin to arise. If the lesion occupies the left PFC, what happens to that information? Does it simply get left unanalyzed and you lose that field in each eye?

In a static environment you could assume that the side affected by the lesion would lose greater processing for that side of the brain. However, if the brain were dynamic and could re-route the circuit, information from that field could have the potential to return. It seems that’s just what occurs but with a small cost. The information destined for the left PFC follows the tradition route back to the prefrontal cortex but stops short, makes a pass through the corpus callosum,  and arrives at the contralateral prefrontal cortex (right side). The right prefrontal cortex actually picks up the slack left from the damaged area. However, as this seems almost too good to be true, this is not the case under all conditions. When an object is detected in the affected field compensation occurs. Yet, when objects are present to both fields simultaneously the right PFC solely analyzes the information from the right field. In other words, the right PFC picks up the slack so long as it has no incoming information itself.

The brain undergoes this change after repeated exposure to left field stimuli on a trial-by-trial basis. While the left PFC never fully recovers, this example shows a rather interesting compensation mechanism that can be achieved plastically. Although the paper never actually discussed this, I can’t help but wonder about the underlying cellular changes associated with this feat. Currently my assumption would just be an increase in synapses (synaptogenesis) favoring the re-wiring across the corpus callosum and to the contralateral cortex. But that’s just my guess. If anyone has any thoughts to the contrary I would certainly be willing to entertain them.

Voytek, B., Davis, M., Yago, E., Barceló, F., Vogel, E., & Knight, R. (2010). Dynamic Neuroplasticity after Human Prefrontal Cortex Damage Neuron, 68 (3), 401-408 DOI: 10.1016/j.neuron.2010.09.018 

*UPDATE*: I figured using ResearchBlogger would be more efficient.

I Think, Therefore I Am

This was a piece written for our Developmental Biology final. I wrote this with the intention of pushing a radical, controversial concept that I had never seen before. This article does not necessarily reflect my own views. This was merely an assignment I had a bit of evil fun with. Enjoy!


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Innate Immunity: So Nice, They Made It Twice

People often use the phrase “do not reinvent the wheel” to describe using an existing method towards a new task rather than creating one anew. Evolution tends to follow a similar philosophy. Many changes utilize genetic toolkits that have long been present, tucked away in the genome of the organism. Sometimes these toolkits have already been used repeatedly for various traits. The common fruit fly (Drosophila melanogaster), a model test subject for over a century, has been scrutinized in remarkable detail to gain an understanding of molecular interactions and evolution. When researchers discovered the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in mammals that functioned remarkably similar to the Toll pathway in Drosophila it was assumed that the immunological pathways were homologous (e.g. using the same toolkit).

The NF-kB pathway establishes its importance due to its swift reaction time. Most transcription factors are synthesized as needed. Building a protein from scratch then applying it where

Figure 1: Contrasting transcription pathways between Drosophila and Mammals

needed takes a fair amount of time. Sometimes, like during a pathogenic invasion, the cell cannot survive long enough to produce these proteins. In the immune system these proteins can be constructed preemptively, bound, and inhibited in the cytosol for future use. The NF-kB pathway activates these stored proteins by cleaving the inhibiting molecule and thus allowing the transcription factor, NF-kB, to enter the nucleus. The Toll pathway operates, essentially, in the same fashion as NF-kB (Figure 1). However, Drosophila uses completely different proteins to ultimately provoke a similar immune response with Dorsal-related immunity factor (Dif ).

The Toll pathway plays another, yet significant role only found in Drosophila. After the egg is

Figure 2: The Toll-Dorsal Pathway in Drosophila melanogaster

fertilized it lays the foundation for the rest of development, ventral and dorsal (down and up). Upon fertilization, the ligand Spätzle (SPZ) is distributed across the perivitelline membrane (Figure 2a). From here, SPZ binds to the Toll receptors of cells maternally designated to become ventral. The Toll receptors set in motion a cascade that phosphorylates CACT (the inhibitor) which allows the transcription factor to promote the production of the protein Dorsal (Figure 2b).

These pathways were initially thought to have arisen from a common ancestor to both Drosophila and mammals. However, it seems this is only partially correct. Genomic research opened up new, previously unexplored areas to consider. This pathway did, initially, form in a Eumetazoan ancestor. This pathway was markedly underdeveloped and only contained a few components. When the bilateral lineage diverged into deuterostomes and protostomes the common pathway ended. From here, both NF-kB and Toll evolved independently through gene duplication.

These diverse differences between pathways give great insight to the evolutionary history of the circuit itself. In order to have diverged so far in composition yet retain similar function suggests the ancestral pathway to have been particularly modular. In other words, the ancestral pathway was constructed using multiple pieces (modules). This setup allows individual modules to be modified over time without removing the core process of the system. Drosophila slowly modified this pathway to affect larval development by introducing Dorsal and SPZ into the circuit. As a result, Drosophila is able to use a single genetic circuit for dual regulation.

In Biology, nothing is ever as simple as it appears to be. The subjects could range from immune response pathways and developmental regulation to simple autosomal point mutations, but more research is always needed. The NF-kB pathway was thought to be well known until just recently, yet new information radically altered our understanding of it. With additional research, who knows what we could uncover next?

Belvin, M. P., Anderson, K. V., 1996. A CONSERVED SIGNALING PATHWAY: The Drosophila Toll-Dorsal Pathway. Annual Review Cell Developmental Biology. 12, 396-416.

Lemaitre, B., 2004. The road to Toll. Nature Reviews Immunology. 4, 521-527.

Leulier, F., Lemaitre, B., 2008. Toll-like receptors — taking an evolutionary approach. Nature Reviews Genetics. 9, 165-178.

Waterhouse, R. M., Kriventseva, E. V., Meister, S., Xi, Z., Alvarez, K. S., Bartholomay, L. C., Barillas-Mury, C., Bian, G., Blandin, S., Christensen, B. M., Dong, Y., Jiang, H., Kanost, M. R., Koutsos, A. C., Levashina, E. A., Li, J., Ligoxygakis, P., MacCallum, R. M., Mayhew, G. F., Mendes, A., Michel, K., Osta, M. A., Paskewitz, S., Shin, S. W., Vlachou, D., Wang, L., Wei, W., Zheng, L., Zou, Z., Severson, D. W., Raikhel, A. S., Kafatos, F. C., Dimopoulos, G., Zdobnov, E. M., Christophides, G. K., 2007. Evolutionary Dynamics of Immune-Related Genes and Pathways in Disease-Vector Mosquitoes. Science. 316, 1738-1743.

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