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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: 12121212

Assignment #1

Florida International University

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Introduction

TBI Trend and Growth

Traumatic Brain Injury (TBI) affects a wide variety of people nationwide. One constant

does remain; the human condition suffers, both internally and externally. Studies confirm that

caregivers of those who suffer from TBI may experience feelings of burden, distress, anxiety,

anger, and recurring depression (Brain Injury Association of America [BIAUSA], 2015). More

detrimental is the alarming number of deaths and disabilities caused by TBI, which contribute to

roughly 30% of ALL injury related deaths in the U.S. (Centers for Disease Control and

Prevention [CDCP], 2014). The effects of TBI can include impaired thinking or memory,

movement, sensation, or emotional function (CDCP, 2014). The ferocity and utter devastation of

those afflicted with this condition are severely hindered in life and in turn the negative prognosis

can have an enduring effect on relatives and even on a community as a whole. 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. Study goals will also encompass current newly invested research at

the University of Miami Miller School of Medicine and the University of Michigan Medical

School so as to further support the indicated research listed above.

Background: Origins of TBI and Impact

TBI is primarily found in patients who suffer from penetrating head injuries that disrupt

the normal function of the brain. It is important to note that not all blows and bumps necessarily

result in TBI formation, but, is based on how serious head trauma is and can range from mild

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(i.e. brief change in mental status) to severe (i.e. an extended period of unconsciousness or major

loss of cognitive and motor function) (CDCP, 2014). According to the CDCP (2014), most cases

of TBI result in mild symptoms, like concussions, but if left unchecked can result in serious

injury or even death in some cases. TBI has a very unpredictable form of recovery and many

factors can contribute to the ultimate outcome, such as, pre-morbid personality and oriented goal

direction of healthcare team and patient alike, length of coma, specific area of the brain or brain

stem damaged, family support, age the injury occurs, and care of specialized rehabilitation

services (BIAUSA, 2015).

General 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). Based on the collection of data by the CDCP (2014), leading

causes of TBI include: Falls (40.5%), unknown (19.0%), struck by/against (15.5%), motor

vehicle/ traffic accident (14.3%), and assaults (10.7%). Data also suggests that falls account for

the greatest reason for TBI from 2006-2010 (CDCP, 2014). Falls also disproportionately affect

the youngest and oldest age groups across the board, although no definitive correlation expresses

causation between the older you are the More likely you are to fall and the younger you are the

Less likely you are to fall and become burdened with TBI.

Specific Problem Statement

The specific problem in TBI is that it can be rooted based on scientific evidence that out

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

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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). As aforementioned in

the previous paragraph, 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. Sometimes good days are followed

by bad days in the ICU and that doesn’t always imply permanent reversals of conditions due to

TBI (i.e. paralysis, mental retardation, comatose, concussion, etc.). Only the University of Miami

Miller School Of Medicine and the University of Michigan Medical School have been able to

successfully immobilize the lingering effects of decreased brain glucose metabolism due to TBI,

as well as, genetically modify neural progenitor cells (NPC’s) in order to increase

histopathological outcomes thus increasing hippocampal neurogenesis in patients who suffered

from Projectile Ballistics Brain Injuries [PBBI] (Bramlett et al., 2015). If clinical professionals

began to implement the models and research methods that have been tested in the lab setting,

then it is ultimately believed that TBI treatment outcomes and prognosis will be headed towards

the right direction.

Purpose of the Study

The purpose of this research will be to gather existing data set for analysis on TBI

research and test the effectiveness associated with transplantation of NPC’s and the results of

localized drug therapy on major traumatic injury sites of the brain. After statistical data has been

compared to those research facilities that are not implementing this treatment methodology,

literature review of information pertaining to efficacy of lab results and extrapolation of data

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synthesis; as to why most research is going to be gearing towards this new path of medicine in

the near future will also be discussed in detail. Overall the researcher hopes to raise awareness of

the achievable goals and positive steps that have been affiliated with this specific type of

research methodology. By examining the impact of the programs at the University of Miami and

the University of Michigan and the integration of existing knowledge in the fields of

neuroscience and emergency medicine, more preventative resources including newly integrated

assessments such as genetically modified pro-survival multi-neurotrophin will be allocated to

this specific type of injury nationwide (Blaya, Furones-Alonso &,Tsoulfas, 2015).

Research Questions

The researcher hopes to address these questions in particular:

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

that have been injected with Chronic A20?

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

expand neurogenesis activity within TBI structures of the brain?

3. 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?

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

neurobehavioral outcomes of PBBI patients (type of TBI)?

5. 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)?

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References

Blaya, M., Furones-Alonso, O., Tsoulfas, P. (2015). Transplantation of Genetically-Modified

Neural Progenitor Cells to Improve Histopathological Hippocampal Neurogenesis:

Attenuates cognitive impairment after traumatic brain injury. Miami Project to Cure

Paralysis. Department of Veterans Affairs Medical Center, University of Miami Miller

School of Medicine. Published on April 2015.

Brain Injury Association of America. (2015). Family and Caregivers: Brain injury affects the

whole family. Baylor Institute of Rehabilitation. Published on February 2015.

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.

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

Retrieved January 29, 2016, from

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

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

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

January 29, 2015, from http://www.ninds.nih.gov/disorders/tbi/detail_tbi.htm