The Root of Thought (22 page)

Brain injury research is messy business; the models to undertake the studies vary between a piston type machine that slams directly onto the brain of a rat or mouse after the skull plate has been removed to a huge anvil that slams onto a massive tube filled with saline, like a syringe that is the size of a barrel of a baseball bat. The experimenters can calibrate the machine to determine how much fluid they want to squirt out. They cut out the skull, drop the anvil, and water sloshes onto the brain, compressing it and causing injury. Both of these models were developed by the automobile industry in the 1970s to better understand what happens to its customers when they drive at 55 mph into a brick wall.

Both of these models produce open-head injury contusions. Closed head injury is achieved by dropping a brass weight onto a metal plate affixed to the top of the skull of the rat brain. These models have provided a variety of cellular information on how to protect axons in the brain.

Another model that looks at rotational forces in the closed head is to put the head of a large animal in a vice and shake it vigorously. Experiments of this type have been unofficially banned because of an incident where researchers were taped performing them on monkeys. Watching this in action if you are not desensitized as the experimenter can lead to complete disgust. However, much of what we know now about the brain after injury, for better or worse, comes from these studies. With these messy models, research on injury is a slow process and compounded by lack of glial research as well.

The studies of cellular genesis have been the most interesting. Many reports have shown that glial cell division eventually results in new neurons in the brains of rats and mice that have been given a contusion injury. A study has yet to determine the amount of astrocyte replacement that occurs after injury in the brain.

Children and infants who experience more brain tumors and astrocyte growth than adults have better recovery from brain injury. If adults could experience similar regeneration, they might also recover better. They might not be able to acquire information from the past, have different personalities, and have to relearn everything they know, but they would have the ability to do so with astrocytes available.

The implications for controlling increased intrinsic cellular genesis is immense. If researchers could somehow determine the responsible mechanism that creates astrocytes to turn over in this manner, they could feasibly repair the brain.

At this point, the idea of recreating neurons with embryonic cells is the prevailing notion instead of trying to understand how to replace astrocytes or influence more constructive astrocyte growth. In the near future, as more studies on astrocytes reveal the nature of their purposes during an insult to the brain, researchers can hopefully bring to light cell-based beneficial treatments for patients.

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Sustaining adequate astrocyte turnover leads to a healthy brain. If astrocytes cannot replace themselves fast enough, a wasteland of ineffective cellular communication occurs and reveals itself in the form of neurodegenerative disease. This wasteland cannot provide an adequate level of consciousness when handling the environmental cues sent to it by the neurons. Astrocytes’ calcium puffs spur the imagination sparkling in our brains. Extra concentration, learning, and thinking might create full calcium waves and spawn additional astrocyte growth. More cells contribute to the ability to handle more complex ideas and process the environment on a higher level. More astrocytes also help a person create more new ideas, like a muscle that can lift more weights because it has been used so frequently.

However, when a trigger causes excessive astrocyte growth—unchecked and robust—a brain tumor results. Like a biblical scourge of pestilent insects, the astrocytes end up destroying everything in their paths. Cells in our brain are asexual like amoebas that breed with themselves. They need energy and nourishment and care for nothing else. The insidious cells multiply like a pile of gremlins tossed in Lake Huron.

Tumors on our body usually originate from cells that are not static, but work to produce fluid or constantly regenerate while dealing with the environment. For instance, breast cancer and testicular cancer arise from cells that produce milk and sperm. Ovarian cancer arises from an organ that produces eggs. Prostate cancer is so prevalent that it is believed that it will occur in any man if he lives long enough. The prostate is an incredibly active gland creating massive amounts of seminal fluid. Two areas that have to regenerate cells to handle the environment most notably are the colon and the lung. High incidence of malignant cancer can form in these two tissues. In the lung, the dirty air
means that constant turnover of cells is needed because of the bombardment they receive from dirt and debris. Similarly, cancer originating in the brain comes from two main types of cells: cells producing fluid and cells that regularly turn over.

About 60 to 70 percent of brain tumors are of astrocyte origin. The other 30 to 40 percent come from the meninges, the cells that produce the ventricular fluid the brain is encased in, the same ventricular fluid used by astrocytes to divide during development and into adulthood. The cells in the meninges turn cancerous because they work like a prostate. Astrocytes produce tumors because they constantly divide and are more likely to have a glitch that would result in the onset of cancer. A tumor comprised of neurons is as rare as being hit by a meteor. The miniscule amount of neuronal-based tumors mainly occurs in the spine and on sensory ends like in the ear. When it happens, there are also glial cells present in the destructive mass. Ependymal cells lining the blood vessels and ventricles form some tumors, but astrocytes are also frequently present in these tumors. Similar to oligodendroglioma, where oligodendrocytes go rabid, astrocytes are frequently mixed in. Tumors in the brain are called gliomas for this reason.

The main malignant brain tumor is called the glioblastoma multiforme. This tumor is a wildly dividing astrocyte-comprised mass that is incredibly destructive. The most egregious aspect to the neuronal focus in the last 100 years has been the complete lack of understanding of the cause of brain tumors. Like all cancer, brain tumors remain incomprehensible. Cancer is a nasty disease, and there is absolutely no cure, but at least in other cancers, the nature of the cell that has morphed into a carcinoma is clear. This was not the case in the brain until recently.

In the early 1980s, glial fibrillary acidic protein (GFAP), the marker for astrocytes, was used in a set of patients with tumors. It was discovered that GFAP labeling existed in glioblastoma multiforme large cells and other tumors of the brain. During injury and disease, increased expression of this protein is noticed. Although the reasons why this protein is expressed are not certain, it might provide some function when astrocytes attempt to divide and proliferate. Glioblastoma multiforme was previously believed to be comprised of embryonic neoplasms—a fancy way of referring to cells that stay with us from the womb, an incredibly bizarre support of Cajal’s idea that the brain stopped dividing after we reach adulthood.

It wasn’t until the World Health Organization’s conference to classify tumors in 1993 that it was generally accepted that astrocytes were likely the main cell that morphed into the large cells in the glioblastoma multiforme tumors. It is known that astrocytes are the main components in these malignant tumors, as well as the second most prevalent tumor, the astrocytoma.

Astrocytomas occur mainly in the cortex. Astrocytes comprise the bulk of tumors in other parts of the brain as well, but research has yet to discover what sets off the transformation process from normal, healthy, pondering astrocyte to rabid, insane, seething, breeding astrocyte.

Without knowing the reason astrocytes become cancerous in the brain, a limited amount of therapy is available. The first treatment is to just cut it out. For instance, Ted Kennedy had a tumor and they just cut it out. If the surgeon is able to get the entire tumor out of the brain, the patient is able to survive for years afterwards. The cells need to be eliminated or they will continue to grow and multiply in the brain. Dracula would have better temperament in a blood bank than a cancerous astrocyte does in your brain.

Some evidence exists that one has a higher chance of developing a glioma if there has been previous instance of brain cancer in your family. However, as far back as the 1950s, a link in families has been discarded as nonexistent. No molecular genetic link has been adequately described, and studies claiming an increase of instances of brain cancer in families might be attributed to the fact that people in the same family are raised in the same environment, and therefore an environmental cause might be the culprit.

One of the creepiest things that occurs when astrocytes are cancerous is angiogenesis, the increase in formation of blood vessels so they can supply themselves with nourishment. Like a guerilla army setting up shop in your skull, the glial cells wrap themselves around warped, newly formed blood vessels and consume all the energy and oxygen meant to keep your brain healthy. The two most common forms of brain tumors—glioblastomas and astrocytomas—have interesting times during the lifespans when their incidence is the highest. Astrocytomas peak in childhood, and the incidence stays steady for the rest of the lifetime through adulthood. Glioblastomas occur at the same time in the lifespan as heart attacks. They begin to become a problem when people turn 30 years old and then the incidence rate increases steadily throughout their life.

The relative paltry research on brain cancer and the cause, combined with a complete focus on neurons in much of the field of brain research, has led to a complete lack of understanding of the disease. Little funding is given to study brain cancer, with more effort and funding put into understanding degenerative diseases. To understand degenerative diseases, one must understand why cells like astrocytes can suddenly freak out and start growing like Jack’s beanstalk.

In the last 20 years, the protein O6-methylguanine-DNA methyltransferase, or MGMT, was discovered to perform the function of gene repair. Gene repair enables cells to be more resistant to death and better able to divide. In the late 1980s, it was shown to exist in the brain and is now known to be expressed in astrocytes and completely absent in neurons.

One of the problems with glioblastoma multiforme is its resistance to chemotherapy and radiotherapy. However, when researchers noticed when the MGMT gene was silenced, they were able to effectively treat the tumor and get much better long-term outcomes in patients.

MGMT seems to be expressed in normal astrocytes and is highly expressed in cancerous astrocytes. The protein repairs the DNA as the cells rapidly divide. With this protein actively maintaining the cells’ capabilities to continue to divide, treatments are fated to pretend.