The blood brain barrier is a filtering mechanism that carries oxygen to the brain

and prevents the passage of undesired substances. This barrier is disrupted after
traumatic injury to the brain. Chronic traumatic encephalopathy is a neurodegenerative
disease found in people with multiple head injuries. This disease is chronic, meaning it
occurs over and over and results in altered sight, memory issues, and changes in
behavior, memory, and emotion. Chronic traumatic injuries can cause brain disorders
later in life such as dementia. When the blood brain barrier is disrupted, edemas and
hematomas can occur, which is an excess fluid buildup and swelling of clotted blood,
respectively (class notes, 2018). The blood brain barrier is also a cerebrovascular
component, dealing with both the vessels and the brain in the central nervous system.
The vessels are composed of lumen-forming endothelial cells that associate with glial
and neuronal units, which form the blood brain barrier (class notes, 2018). This is what
is known in the central nervous system. The glial cells studied are astrocytes and
pericytes and the neuronal cells studied are cortical vascular endothelial cells. Also in
the CNS, macrophage cells and endothelial progenitor cells were studied. What is
unknown and being investigated is whether dependence receptors have a role in
regulating vessel stability and the blood brain barrier. The dependence receptor,
EphB3, is a pro-apoptotic receptor that binds to the ligand ephrinB3. This ligand when
bound to the EphB3 receptor decreases cell death, suggesting that ephrinB3 effects are
EphB3 receptor mediated. The presence and absence of the EphB3 receptor was
analyzed in astrocytes and pericytes to determine if glial membrane interactions with
cortical vascular endothelial cells increased. Also, macrophage and endothelial
progenitor cell infiltration was examined with EphB3 present and absent to determine
whether this receptor increased or decreased blood brain barrier permeability.
There was an article related to the disruption of the blood brain barrier after
traumatic injury. The focus of the article was on leptin-deficient receptor mice that had
blood brain barrier breakdown, which caused macrophage infiltration leading to
cognitive impairment. When the blood brain barrier was disrupted, its permeability
increased, allowing macrophage infiltration. Cognition is then impaired due to the
macrophage infiltration because the macrophages engulfed parts of the brain. This
caused thought processes to be damaged or slowed (Stranahan et al., 2016). The
cognitive impairment occurred in mice with type II diabetes because they were obese.
Obesity was caused by deficiency in leptin receptors. Leptin is a protein that regulates
fat storage by regulating signals to the brain that provides a feeling of satiety. Since the
receptor was not present, the mice tested never felt satiety and ended up overeating.
Flow cytometry analysis was used to reveal macrophage infiltration and induction of
MCHII in macrophages. MCHII is found on mononuclear phagocytes and serves as a
macrophage marker (Stranahan et al., 2016). Flow cytometry was also used in the
original article studied and this technique analyzed macrophage infiltration and
endothelial progenitor cells. This article builds upon the information of the original
article being critiqued because it gives insight to another receptor in the brain called
leptin receptors. Absence of these specific receptors can cause obesity, which
accelerates cognitive decline because the blood brain barrier increases permeability
(Stranahan et al., 2016). If an obese subject already has increased permeability without
cortical controlled impact or traumatic brain injury, then post-injury could be more fatal.
After traumatic brain injury in an obese subject, EphB3 signaling could cause even more
endothelial cell death because the blood brain barrier was already disrupted prior to the
traumatic brain injury. This could result in permanent damage or death as compared to
a brain disorder that occurs in a later stage of life. Figure. 6 in the original article being
critiqued demonstrates macrophage infiltration being reduced with the absence of the
receptor EphB3. Absence of EphB3 receptor in the brain could repair cognitive function
in leptin-receptor deficient subjects because less macrophages would be engulfing brain
regions.

Stranahan, A. M., Hao, S., Dey, A., Yu, X., & Baban, B. (2016). Blood–brain barrier breakdown
promotes macrophage infiltration and cognitive impairment in leptin receptor-deficient
mice. Journal of Cerebral Blood Flow & Metabolism,36(12), 2108-2121.
doi:10.1177/0271678x16642233

Fornsaglio, J. 2018. Class notes