Assignment #4 (Findings/Data)

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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 #4

Florida International University

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Findings

To date, Traumatic Brain Injury (TBI) still remains as the nation’s leading cause of death

and disability in both young children and adults (Center for Disease Control and Prevention

[CDCP], 2014). It is without reservation that I continue to seek the truth and extensive

knowledge behind the overall treatment prognosis or effectiveness of Neural Stem Cell

Transplantation for patients suffering from this severe and detrimental neurological disorder.

Based on the limited number of studies developed for TBI treatment using this technique, the

analysis of literature reviews, and the implications of the methods used to successfully localize

drug therapy in affected brain regions, I feel very confident and secure in knowing that this

modality of treatment has in fact produced the best results within the controlled laboratory

setting within the last decade. But, even with appealing positive scientific results, this method

incurs its own set of limitations, its distinct applicative methods, and most of all, its own

drawbacks and discrepancies within the clinical environment. The continuation of this paper will

address the items aforementioned above, as well as list the necessary recommendations to keep

Neural Stem Cell Engraftment research at the helm of more improved and effectual TBI

research.

Limitations

Although Neural Stem Cell Transplantation has proven to be effective in ameliorating

TBI conditions in lateral portions of the brain, the scope and overall advances of this treatment

do come with a hefty price tag as well as a very tedious and time consuming treatment pattern.

According to Dr. Ross Bullock (2016), his four year research study will cost his department

more than 4.2 million dollars and more than 25 clinical staff at The University of Miami Miller

School of Medicine. Additionally, Neural Stem Cell engraftment techniques only work under

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strict conditions. If these conditions were not met during the treatment process, than exacerbation

of the condition would ensue and more harm would be done then actual good (Bullock, Dietrich

& Gajavelli, 2016). Optimal location site, maximum amount of tissue engraftment, secondary

injuries, blood type, clotting factors, time window, and highest cellular concentration count must

all be met prior to making neural stem cells or neural progenitor cell therapy a viable treatment

option.

Use and Applications of Findings

The use and application of Neural Stem Cell engraftment therapy is primarily situated for

patients who suffer from aggressive forms of TBI such as Projectile Ballistics Brain Injury

(PBBI) or severely advanced forms of neuronal cell apoptosis. Thanks to hypothermic

conditions, researchers have also found positive clinical results in reducing Inter-cranial

Hemorrhaging (ICH); diminishing the effects of immune-histo-globins secondary injury effects

and neurodegeneration of white matter in traumatic brain regions, with medicated localized drug

therapy help to proliferate neurogenesis of dead lateral tissue (Bramlett et. al, 2015). With these

findings, there is now a possible scenario that clinical scientists can create in order to maximize

the transplantation of neural stem cells in heavily damaged areas of the brain. This well-

developed research methodology is now the cornerstone of TBI research, it encourages families

and patients alike that there is actual hope of a treatment protocol than can lessen or reduce the

consequential effects of this painstaking neural condition.

Recommendation 1

As I mentioned above, one of the greatest challenges to overcome when conducting TBI

research that involves NSC treatment is the great cost that is needed to pursue it in the first place.

As of right now, the greatest contributor of TBI research worldwide is the National Institute of

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Neurological Disorders and Stroke (NINDS). Could you imagine that? One of the premiere

treatment options and only ONE significant source of funding for it! The best way to combat this

is to publicize more scientific journals that speak volumes about the progression of NSC

engraftment and the wonders that it is doing in the lab setting. By getting more data out to the

general public; more private, university, or even state and federal government funding may

become available in order to combat the ever growing trend of TBI based death and paralysis

nationwide. As of now, only two universities are conducting TBI research with NSC treatment at

the head of their respective departments. Both universities have combined for a grand total of 50

million dollars thanks to the donation of the NINDS, which only makes up 10 percent of their

overall budget for funding allowances (NINDS, 2016). We have got to get the ball rolling if we

want to see an impact in better treatment outcomes.

Recommendation 2

Time truly is of the essence, and there is no area more prevalent than the fight against

TBI related illnesses. According to the NINDS (2016), most institutions who have adopted a

research modality for TBI enhancement regularly do not see results from their clinical lab work

until seven years after their funding has been allocated. You don’t have to be an expert Neuro-

Anatomist to conceptualize the notion that the brain is a tough organ to understand and even

harder to actually get a hold of. One of the main reasons attributed to why research takes so long

is that the findings of cures or better treatments aren’t done cohesively within the nation.

Institutions of higher education, pharmaceutical companies, and other outside sources are

competing against one another, rather than taking action together towards the same cause.

Because the health field and clinical research realm are so profit based, everyone is looking for

the best possible way to make money and garner fame, rather than think about bringing everyone

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in on the same research updates, techniques, and assessment data. We need to give up the selfish

motives and begin to think about the patients and families who are suffering; those are the people

who we should be fighting TBI for.

Recommendation 3

Neural Stem Cell engraftment for the most part is a tricky and complicated way to want

to help out the brain. EXACT and PRECISE steps must be taken to ensure that positive

histopathological outcomes are met throughout the entirety of any research being conducted. One

of the best ways to facilitate this treatment option is to introduce foreign agents into the brain

that will alert Red Blood Cells (RBC) and White Blood Cells (WBC) to infiltrate the foreign

body and attack it. As a researcher, it is important to inject a substance that will not damage

tissue and that can be readily digested by the brain’s macrophages. By doing this and alerting the

anti-inflammatory responses of the lateral or ipsilateral portions of the brain, the brain will reach

a heightened state of inflammation which is when cell count is at its highest. Meaning that would

be the optimal timeframe to inject NSC either in the rostral or caudal sections of the brain. Its an

effective precursor to use when treating TBI sections and becomes more potent when done

during hypothermic conditions.

Conclusion

There are a myriad of findings and collected works that represent NSC engraftment

treatment as a substantial and credible source of attenuating TBI portions of the brain. By

helping to facilitate localized drug therapy at specific origin sites, NSC therapies will

undoubtedly be the epicenter for TBI treatment effectiveness within the next decade. According

to Dr. Williams et. al, (2005) from the University of Michigan Health System, his clinical report

of NSC treatment and engraftment for TBI induced mice was conducted by evaluating the

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pathophysiological consequences of a temporary cavitation injury to the rat TBI brain, designed

to simulate the unique injury pattern produced by a penetrating ballistic head injury. The most

distinct pathologies associated with PBI were the presence of ICH, a hallmark of PBI, and

extensive zones of cell death radiating into mechanically intact brain regions. Overall, a

significant and reproducible brain injury was observed in the form of both gray and white matter

tissue damage and related neurological impairments, sensitive to the degree/type of injury.

Furthermore, the model appeared to possess significant clinical relevance as related to the

histopathological presence of a region of NSC surrounding the lesion. Several

pathophysiological indicators of secondary injury were also present including brain swelling,

increased Inter-cranial Pressure, brain seizures, persistent Cerebral Spinal Damage, and neuro-

inflammation. In effect, several salient aspects unique to a penetrating type injury have been

modeled, offering a valuable vehicle for the pre-clinical study of PBI to help improve patient

outcomes when relevantly treated with NSC at maximal engraftment sites (Williams et. al,

2005).

According to Dr. Hellen Bramlett (2015), her research has demonstrated the overall

impact of regulating neurogenesis in the midbrain level of over 3, 200 rice models using NSC

stimulation for PBBI affected bregma regions during later years of the developmental cycle. The

prognosis of survivability is relatively high, reaching 81 percent of total mice population, and the

condition of neurogenesis was more evident in mice with higher levels of damaged brain that

could not heal on its own (Bramlett et. al, 2015). The efficacy of NSC engraftment treatment was

available due to the injection of CA20, an FDA approved drug that helps facilitate anti-

inflammatory responses within the brain, thus positioning the brain to receive NSC treatment at

its most efficient peak during the latent moments of cell recuperation. This proves that following

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TBI, repair mechanisms do exist when cognitive function in damaged brain is apparent,

especially when the brain is induced with a steady rate of NSC and CA20 compound in order to

proliferate the existence of neurons even when such high injury sites are localized (Bramlett et.

al, 2015).

Lastly, my own assessment of NSC treatment was also conducted when quantifying the

results of white matter neurodegeneration when TBI exposed brain tissue was stained with a

Bielchowsky Modified Lester King Silver Stain Kit. Within my research I was able to visually

quantify the appearance of neural cell death of a PBBI induced rat brain, one was parifinated

sample (control group) was compared to a 6 week infused NSC tissue sample (experimental

group). After my experimental analysis was conducted, I could with a 95 percent confidence say

that NSC engraftment treatment did in fact halt the secondary effects of PBBI, most notably, that

of neural cell apoptosis. This was able to be conducted after localized drug therapy was

monitored within the 0.1-0.4 bregma regions, in which dead lateral tissue was at its highest,

which presumably pointed out to be the most highly damaged site and neurogenesis was being

performed at a higher rate here. When injecting NSC on unhealthy tissue in live rat samples,

areas where glucose metabolism was at its lowest meant higher portions of neurogenesis which

correlated to the higher areas of NSC around the surrounding tissue. Overall, the efficacy of

treatment is rather positive, and I can expect within the following years to come, to see NSC

engraftment therapy as the tip of the sword in TBI research and the best clinical solution for all-

inclusive effective treatment.

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References

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 April 6, 2016, from

http://www.cdc.gov/traumaticbraininjury/get_the_facts.html

Dave, J., Hartings, J., May-Lu, X., Rolli, M., Tortella, F., Williams, A. (2005). Journal of

Neurotrauma: Characterization of a new rat model of penetrating ballistic brain injury.

Department of Neurotrauma. University of Michigan School Medicine. Published on

November 2, 2005.

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National Institute of Neurological Disorders and Stroke. (2016). Transforming Research and

Clinical Knowledge in Traumatic Brain Injury. Published on January 2015. Retrieved

April 6, 2015, from http://www.ninds.nih.gov/disorders/tbi/detail_tbi.htm