The Outcomes of Neural Stem Cell Transplantation and Localized Drug

Therapy on Patients Suffering from Traumatic Brain Injury

Elaborate and discuss these statements in a detailed form.

Traumatic Brain Injury (TBI) affects a wide variety of people nationwide. One constant does remain; the human condition suffers, both internally and externally. The proposed study will review current literature and collective research models and data based on neural stem cell transplantation on injured brains and their positive outcomes; as well as, the facilitation of newly implemented procedures for localized drug therapy on their respective injury sites. Studies are primarily collected in controlled laboratory setting and modeled on mice for efficacy of desired treatment protocol as well as the clinical setting being modeled on Projectile Ballistics Brain Injury (PBBI) patients.

Pertinent research questions include: Is there sufficient clinical evidence to support that

the usage of neural progenitor cells expand neurogenesis activity within TBI structures of the

brain? As well as, What are the effects of neural stem cell transplants on endogenous neurogenesis

and neurobehavioral outcomes of PBBI patients? Data analysis was collected by reviewing TBI

literature under different treatment circumstances such as hypothermic, neurodegenerative,

immuno-compromised, behavioral standards, and lastly by quantifying the rate of neural cell

apoptosis within a 6 week period measured at 95% CI (α < p-value = 0.05). Overall the research

hopes to raise awareness of the achievable goals and positive steps that have been affiliated with

this specific type of research methodology.

PROBLEM STATEMENT

The general problem is represented with the figures provided by the CDCP in 2010;

about 2.5 million Emergency Department (ED) cases were associated with TBI; either presented

singly or in combination with another injury here in the United States (CDCP, 2014). TBI was a

diagnosis in more than 280,000 hospitals and of those cases 50,000 ended in death before and

while at the ED (CDCP, 2014). TBI’s rooted issues are based on scientific evidence that out of the

73 institutions currently focused on TBI research, only three are using neural stem cells to

promote neurogenesis in the brain and out of those three institutions, only two have a drug

approved by the FDA that increases glucose activity in injured bregma regions of the brain

(National Institute of Neurological Disorders and Stroke [NINDS], 2016). TBI is a major source

of death and disability here in the US; not only does it account for a large portion of ED care and

attention, treatment procedures and positive outcomes in today’s world of modern day medicine

are very sporadic in nature and thus can be emotionally devastating on the family of the afflicted

patient.

RESEARCH QUESTIONS

• Is there a correlation between increasing brain glucose utilization on affected TBI mice

that have been injected with Chronic A20?

• Is there sufficient clinical evidence to support that the usage of neural progenitor cells

expand neurogenesis activity within TBI structures of the brain?

• Does surgical intervention create better treatment outcomes than injected NPC’s and

Schwann cells within the brain stem on TBI patients over an extended period of time?

• What are the effects of neural stem cell transplants on endogenous neurogenesis and

neurobehavioral outcomes of PBBI patients (type of TBI)?

• In regards to PBBI patients, how does delivery of optimal site and cell concentration to

produce maximal engraftment of neural stem cells increase motor and cognitive behavior in rat

model (brain function similar to humans)?

LITERATURE REVIEW

I hope to express to potential readers the efficacy of neural stem cell engraftment

treatment on patients who suffer from Traumatic Brain Injury (TBI) and by leaning on this form of

treatment the likely outcomes it can play on society as a whole. With respect to the cumulative

objective of this research, the literature indicates that work is being conducted on transgenic NSC

mice that have shown consistently to improve performance in multiple levels of cognitive

domains. This gradual recovery process in mice is associated with NSC expression of brain

derived neurotrophic factors , restores depleted levels and modulates glutamatergic [modulates

protein construction and synthesis] systems in the brain (Atkins, Gajavelli, Herdeen, 2016). Also,

research has shown that without a doubt in more than 3,200 laboratory controlled mice NSC

injection and engraftment has led the way in increasing neurogenesis productivity at later stages in

the development cycle. By assessing optimal site, time, and cell concentration to produce maximal

engraftment of NSC’s in a wide variety of TBI procedures, physicians can verify the best possible

treatment options and in turn medical errors due to TBI procedures can be reduced respectively.

METHODS

OVERALL METHODOLOGY 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 report 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. Most of the data collected by lead investigators in the fields of Neuroscience, Emergency Medicine, Neurosurgery and Neuro-trauma are obtained through quantifiable means, therefore, I will be surveying and scrutinizing quantifiable numerical data that demonstrates a positive progression for affected TBI patients within the lab setting.

FINDINGS

BREAKTHROUGHS

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. The most distinct

pathologies associated with PBI were the presence of

ICH, a hallmark of PBBI, 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. 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). 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.

LIMITATIONS

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 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.

Potential Peer Review Journals For

Publication

– Journal of Neurotrauma

– Journal of the International Neuropsychological Society

CONCLUSION

All impactful models appeared to possess significant clinical relevance as related

to the histopathological presence of a region of NSC surrounding the lesion during

engraftment procedures. 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 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). 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. 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