The Outcomes of Neural Stem Cell Transplantation and Localized Drug Therapy on Patients

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The Outcomes of Neural Stem Cell Transplantation and Localized Drug Therapy on Patients

Suffering from Traumatic Brain Injury

John Doe

Panther ID: 1212121

Assignment #3

Florida International University

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Method

Traumatic Brain Injury (TBI) is a resonating issue here in the U.S. and it comes as no

surprise that it has increased in awareness as one of the nation’s most prevalent injury related

deaths within the last 15 years (American Speech-Language-Hearing Association [ASHA],

2009). It is an illness of great importance due to its association of injuries related to military

combat operations, both the Department of Defense (DoD) and Veteran Affairs (VA) are

recognized leaders in TBI care and are in constant joint health practices with research based

universities such as The University of Miami Miller School of Medicine and The University of

Michigan Health System [UMHS] (Dennis, 2013). My methods paper will incorporate a holistic

overview of the overall effectiveness of Neural Stem Cell (NSC) engraftment on TBI patients

based on publications reported within scholarly journals. The overall efficacy of treatment will

be compared to many control groups that serve as a basis to see if NSC outcomes lessen or

diminish possible injuries, as a disclaimer, findings within TBI based research do not support nor

condone that there is a cure to secondary injuries such as comas, neuronal cell death, loss of

motor or cognitive function, paralysis, or even death due to TBI. Simply put, this research paper

will look at collaborative efforts that a controlled laboratory setting has made in regards to

ameliorating TBI conditions in either acute or severe injuries and review the success of treatment

in the hopes that it can serve patients and their respective loved ones in finding more adequate

treatment platforms that can efficiently save lives in the long run.

Research Method & Design Appropriateness

According to Martyn Shuttleworth (2008), the top three most widely used research

methods are Experimental Research Methods, Opinion Based Research Methods, and

Observational Research Methods. There are a myriad of factors to take into account and evaluate

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when choosing the correct research method. Every experimental design must make compromises

and generalizations, so each individual researcher must minimize these, but, also do it while

being realistic (Shuttleworth, 2008).

Experimental Research Methods is a more straightforward experiment that involves the

standard practice of manipulating quantitative data and independent variables to generate

statistically analyzable data. The results generated can be quantified using a testable hypothesis,

with statistical information giving a clear and unambiguous picture (Shuttleworth, 2008).

Opinion Based Research Methods generally involve designing an experiment and collecting

numerical data that that can be represented via ordinal or interval types of measurements.

Questionnaires fall within this type of experimental method, since it is an effective way to

quantify data through a small sample survey and can provide a scale of opinion to emotion.

“Figures are arbitrary, but at least give a directional method of measuring intensity”

(Shuttleworth, 2008). Based on reports gathered by Shuttleworth (2008), Observational

Research Methods mostly involve researchers detaching themselves from the experiment and

simply witnessing the phenomenon they are most interested in. It’s characterized as a “quasi-

experimental” design and is primarily looked down upon in the scientific community. It oftenly

does not look to have a clearly defined research problem and questions may arise during the case

study, but, according to social scientists it does still provide insightful human knowledge when

applied to behavioral outcomes.

Quantitative research measurements encompass scientific data being strictly inputted into

statistical and other mathematical markers and definitions so as to finalize results via disproving

or proving a hypothesis. After statistical analysis of the data is done, a comprehensive answer

can be reached and the results can be legitimately discussed and published. Qualitative research

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is a fundamental tool that can be used by scientists and social scientists alike as a precursor to

quantitative research. It seeks to answer human behavior and tendencies that can then lead to a

testable hypothesis, since its techniques are extremely useful when a subject is too complex to be

answered by a simple yes or no hypothesis (Shuttleworth, 2008).

For the specifics of my research proposal, as discussed earlier, I will be analyzing

literature content on treatment viability of NSC in those who are afflicted with TBI. Most of the

data collected by lead investigators in the fields of Neuroscience, Emergency Medicine,

Neurosurgery and Neuro-trauma are obtained through quantifiable means. So for the sake of my

literature review, I will be surveying and scrutinizing quantifiable numerical data that

demonstrates a positive progression for affected TBI patients within the lab setting.

Population

Each year TBI contributes to a substantial number of deaths and cases that attribute to

permanent disability within the continental U.S. Within my study, because data is so crucial to

understanding the overall implications of this debilitating condition, attenuating impacts of TBI

can only be lessened with numbers that demonstrate the positive progression of feasible NSC

treatment in localized target areas of injured brain. Gaining information from a wide range of the

diverse population within the United States means heightening awareness of this very prevalent

public health dilemma. The Center for Disease Control and Prevention (CDCP, 2014), reports

that information regarding how TBI affects patients nationwide helps to inform TBI prevention

strategies, identify education strategies and research priorities, and helps to support the need for

services among those living with TBI. According to the CDCP (2014), more than 1.7 million

Americans sustain a TBI annually. More than 275,000 cases of TBI were hospitalized in

Emergency Departments, of those cases, 58,000 ended in death (CDCP, 2014).

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Another alarming population to take into consideration is gunshot victims that have

suffered a form of TBI known as Projectile Ballistics Brain Injury (PBBI). Florida in comparison

to other states has had the largest annual firearm-related fatality rate increase within the past

decade (Bramlett et. al, 2015). No current forms of therapy, other than invasive and life-

threatening surgery are available for PBBI based patients. This only further urges my point that

in order to begin to implementing a grand procedural design for national TBI treatment; its

innovative research at The University of Miami Miller School of Medicine at the local level that

must be able to explore additional treatment options due to the epidemic proportions of firearm

related PBBI in modern American society (Bramlett et al., 2015).

Sampling Frame

Based on the information collected, many sample sizes were collected since NSC

treatment has been tested under many circumstances, such as, hypothermic conditions, glucose

metabolism deprived brains, stroke induced brains, PBBI brain samples, and medically

synthesized brain tissue has been tested as well. Each individual test had its own treatment

methodology and comparable control group. The most recent extracted sample was obtained by

testing NSC engraftment measures on 18 Sprague-Dawley Laboratory mice. The control group

consisted of healthy brain tissue that was parrafinized (held in hydrocarbon wax sheet), and

PBBI tissue was held free-floating in wall plates via cryostat (machine meant to hold tissue at

relatively low temperatures). Both the control and independent variable group were looked under

100x objective lens microscope, both groups was seen to uncover which had developed more

neurodegeneration (neuronal cell death which is irreversible and is stained black) after a six

week period of being treated with NSC (Bullock, Dietrich &, Gajavelli, 2016).

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Data Collection

Data collection was not such an arduous task as most of the quantifiable data could be

extracted via public research articles. However, the analysis of NSC treatment effectiveness and

the necessary range that is needed to claim it as a success was very difficult, being that statistical

methods and Neuroscience are not my fields of practice. The integrity of the publicized works

were maintained by strictly pointing out and upholding the notion that advances in medical care

depend on rigorous, reliable and reproducible basic/clinical and translational research. The

scientific method used in NSC engraftment procedures and maintenance was predicated on being

able to test well-though-out study designs/hypothesis with meticulous data recording and

statistical data of the analysis.

The information I collected was also compared to The University of Michigan Health

System’s records on Neural Progenitor Cell (NPC) enhancement due to TBI related spinal cord

injury under similar conditions and approaches of that of UM Miller School of Medicine. Also, I

was part of the research conducted under Clinical Director Dr. Ross Bullock that measured the

potency of NSC treatment by comparing samples of PBBI brain that induced less

neurodegeneration along the pre-cortical track of the brain. Therefore, I understand the relevance

of the core scientific values of truthfulness, objectivity, unbiased and complete reporting of the

study results.

Data Analysis

Based on the quantitative measures that were needed in order to test the attainable goals

of my research methodology, I can with 95 percent confidence say that NSC engraftment

treatment does in fact diminish the secondary effects of immune-histo-globins (anti-

inflammatory response), neurodegeneration of white matter in traumatic brain and with

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medicated localized drug therapy help to proliferate neurogenesis of dead lateral tissue. Based on

my experimental analysis of neurodegeneration, I concluded that in normal brain

neurodegeneration occurs at a rate 10 percent less than neurogenesis. However, in unhealthy

tissue injected with NSC’s in 18 separate Dawley rats within a 6 week time frame,

neurodegeneration rose to an alarming 22 percent for the first three weeks, but, within the last

three weeks neurodegeneration was brought down to 8 percent and neurogenesis also rose by 11

percent on the bi-lateral portions of PBBI induced surfaces.

I based my values off of a standard mean and sample size intended to run a t-test. I

observed a p-value that was less than my alpha (comparative value) and was able to reject my

null hypothesis with a 95 percent confidence interval based on my sample proportion.

Additionally, according to Bramlett et al. (2015), vehicular pre-clinical studies of PBBI induced

mice show that under hypothermic conditions attenuation of inter-cranial pressure, neuro-

inflammation and inter-cranial hemorrhage were present within brain injury, but, its severity

grew at a lesser rate by a stall of 72 hours. Also, when injected with NSC into the caudal section

of the mouse brain, PBBI mice were able to “walk” onto a balance beam, albeit, they relied

heavily on the pathway of the balance beam rather than coordinated motor capacities (Bramlett et

al., 2015). Still this further demonstrates that the pre-clinical study shows an ambitious and

meaningful pathway to improved future patient health outcomes.

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References

American Speech-Language-Hearing Association. (2009). Current Perspectives on TBI.

Retrieved March 22,2016 from http://www.asha.org/aud/articles/CurrentTBI/

Bramlett, H., Bullock, R., Diaz, J., Gajavelli, S., Jackson, C., Spurlock, M., et al. (2015).

Penetrating Ballistic Brain Injury Reduces Focal & Global Brain Glucose Utilization: A

C-2DG autoradiography study in a rat model. Miami Project to Cure Paralysis,

Department of Nuerosurgery, University of Miami Miller School of Medicine. Published

on June 2015.

Bramlett, H., Bullock, R., Diaz, J., Gajavelli, S., Jackson, C., Spurlock, M., et al. (2015).

Penetrating Ballistic Brain Injury Systems and Methodology: A hippocampal

regenerative effect study in a rat model. Miami Project to Cure Paralysis, Department of

Neurosurgery, University of Miami Miller School of Medicine. Published on June 2015.

Bullock, R., Dietrich, WD., Gajavelli, S. (2016). Penetrating Ballistic Brain Injury Systems and

Methodology: Optimal maximal engraftment of human NSC’s via surgical intervention

or localized therapy injection. Miami Project to Cure Paralysis, Department of

Neurosurgery, University of Miami Miller School of Medicine. Published on February

2016.

Center for Disease Control and Prevention. (2014). Traumatic Brain Injury. Retrieved March

22, 2016, from http://www.cdc.gov/traumaticbraininjury/get_the_facts.html

Dennis, K. (2013). DoD/VA Common Definition. Audiology and speech pathology service.

Department of Veterans Affairs, Washington. D.C. Published on November 2013.

Shuttleworth, M. (2008). Different Research Methods. Retrieved Mar 22, 2016 from

Explorable.com: https://explorable.com/different-research-methods