Lexi Gassman

Cell Biology
Dr. Fornsaglio
TBI critique

Traumatic brain injury (TBI) is known to cause damage to the cerebrovascular network,
which is a vessel network that is made of veins, capillaries, and arteries (Fornsaglio, 2018). The
cerebrovascular network lining is made of lumen-forming endothelial cells which help nourish
the brain. TBI is a disorder that occurs after an individual receives blunt trauma to the head
causing injury to the brain. If the injury is severe enough, the blood brain barrier (BBB) can be
disrupted. The BBB is usually hard to penetrate however, when it is disrupted there can be
leakage into the brain leading to brain edema, hematomas, other secondary injury pathologies
and neurological dysfunction (Fornsaglio, 2018). The BBB is a filter mechanism in the central
nervous system (CNS) that is made up of capillaries. It carries blood to the brain and the spinal
cord. It is made up of endothelial cells that form tight junctions. The BBB becomes easier to
penetrate when an injury occurs. The BBB prevents certain substances from entering the brain
while also preventing certain substances from leaving the brain (Fornsaglio, 2018). There are
receptors and ligands present on the membrane of endothelial cells. Erythropoietin-producing
human hepatocellular (Eph) and their ligands, ephrin, are membrane-bound proteins that
interact and introduce bidirectional signals in ligand and receptor containing cells. Blood vessel
express various Eph receptors and ligands that help to regulate angiogenesis and angiogenic
remodeling. Eph receptors have apoptotic responses after traumatic CNS injury and are
classified as dependence receptors. Dependence receptors are transmembrane proteins that
have different roles depending if the receptors ligand is present. When the ligand is not present,
the dependence receptors will induce cell death and play a role in increased BBB damage. When
the ligand is present, the receptor will have normal tissue and development which will lead to an
increase in cell survival and reduced BBB permeability. The mechanism for receptors and
ligands in endothelial cells of the BBB are EphB3 and the ligand eprinB3. Studies show that
EphB3 is a dependence receptor that helps in the regulation of the BBB and blood vessel
integrity after controlled cortical impact (CCI) injury was inflicted on mice. EphB3 receptors
work as apoptotic receptors in the endothelial cells and contribute to increased BBB damage
after CCI injury is inflicted. When the receptors, EphB3, are absent or their ligands are present
there is an increase in survival of endothelial cells and reduced BBB permeability. It is unknown
if EphB3 is the only dependence receptor that plays a role in BBB disruption after TBI occurs.
There have been two receptors identified, EphB3 and EphB4, that have expressed dependence
receptor functions after there is an injury to the CNS.
Traumatic brain injury is the leading cause of death and disability in childhood (Prasad,
Swank, & Ewing-Cobbs, 2017). Children who suffer from traumatic brain injury face increased
academic challenges and poor development of academic skills. Children with either severe or
moderate TBI are significantly more likely to receive school support services. This article focuses
on better understanding the impact that TBI can have on children by looking at the severity of
the injury, age they were injured, and the long-term effects on school work after injury (Prasad,
Swank, & Ewing-Cobbs, 2017). In comparison to healthy children, those that have suffered TBI
have been reported to have difficulties in almost all the academic areas studied, including math
and reading. The research presented has given insight into the spectrum of symptoms and
disabilities that can result, depending on the severity of the trauma. The constant in most brain
injuries is the disruption of the BBB and the blood vessels. There can be neurological
dysfunction when the BBB is disputed which can result in children suffering academically
(Prasad,et al., 2017). In TBI that is severe or moderate, the BBB and blood vessels are constantly
getting disrupted and their integrity is decreasing. Disruption of tight junctions, widening of
intracellular spaces, and loss of brain endothelial cells all can contribute to the breakdown of the
BBB and the leakiness of the blood vessels when TBI occurs.When TBI occurs chronically, the
integrity of the BBB is significantly lower than what it should be. There are a variety of
disabilities, such as difficulties with memory, thinking, reasoning, and expressing or
understanding information, that can result depending on the degree of trauma. These
disabilities are most prevalent in school-age children who suffer from TBI. In conclusion, TBI
can lead to damage to the BBB, which in some cases results in life altering impairments. Further
research into TBI, EphB3 receptors and the impact on school-aged children is needed to
improve the lives of those impacted by TBI and possibly prevent development of disabilities.
References:

Assis-Nascimento, P., Tsenkina, Y., & Liebl, D. J. (2018). EphB3 signaling induces
cortical endothelial cell death and disrupts the blood–brain barrier after traumatic brain
injury. Cell Death & Disease,9(1). doi:10.1038/s41419-017-0016-5

Prasad, M. R., Swank, P. R., & Ewing-Cobbs, L. (2017). Long-Term School Outcomes of
Children and Adolescents With Traumatic Brain Injury. Journal of Head Trauma
Rehabilitation, 32(1). doi:10.1097/htr.0000000000000218