Page 96 - Read Online

Marcet et al. The inflamed CNS takes hits centrally and peripherally

allows a CCR6 independent pathway of recruitment of ROLE OF THE SPLEEN AS A MAJOR
T cells to the brain parenchyma in the EAE model. PERIPHERAL INFLAMMATORY
[64]
CCL20 expression is upregulated by proinflammatory CONTRIBUTOR TO CNS INJURY
cytokines IL6, and IL17. [65]
Function of the spleen
In a lateral fluid percussion model of TBI, Das shows It has been shown that the spleen initiates an immune
that CCL20 expression is upregulated in the thymus response that exacerbates the pathology of stroke
and spleen 24 h after TBI, and upregulated in the and TBI, however the connection between brain injury
cortex and hippocampus 48 h after TBI. Based and a splenic response has yet to be fully elucidated.
[27]
on the evidence obtained from the EAE model, this The spleen has several functions in the body. It is a
suggests a mechanism for peripheral involvement major lymphatic organ that lies within the peritoneal
in neuroinflammation. [27,28,64] The fact that CCL20 is cavity; it actively monitors the body’s circulation and
expressed in the spleen and thymus after TBI, before it filters blood. [68,69] In humans, the spleen plays a role
is expressed in the brain, and brain CCL20 expression in the mononuclear phagocyte system, recycles iron
is reduced in rat’s who’s spleens have been removed from old red blood cells, and mounts a defense against
suggests a peripheral mechanism of activation for blood borne pathogens. [69,70]
CCL20 expression in the CNS. It also speaks to the
[27]
role that CCL20 plays in neuroinflammation after TBI. The spleen as a reservoir of systemic
In other words, CCL20 upregulation in the spleen and immune cells
thymus after TBI could indicate a peripheral signal that The spleen is also a reservoir of platelets, peripheral
drives neuronal degeneration. [27] macrophages, and other immune cells. [28,70,71] Scientists
used to think that the majority of monocytes patrolled
In stroke, we see a similar peripheral involvement the circulation, and irreversibly differentiated into
in chronic inflammation after insult. Nguyen and macrophages and dendritic cells upon extravasation
colleagues characterized the cytokine profiles in mice and tissue entry. It is now known that the spleen
[70]
after ischemic CNS infarct, and showed a polarized actually acts as a reservoir for undifferentiated
T cell response based on the type of mouse used. monocytes, and monocytes in the spleen outnumber
[66]
C57BL/6 mice had a Th1 polarized response, and monocytes patrolling the circulation. [68,70] This means
BALB/c mice had a Th2 polarized response. This that a majority of undifferentiated monocytes reside in
[66]
suggests that the chronic inflammatory response the spleen, waiting to be deployed. Monocytes, distinct
in stroke patients could follow different courses, from macrophages and dendritic cells, cluster in the
depending on the individual afflicted. [66] cords of the subcapsular red pulp of the spleen. [70]

In all of these instances, peripheral involvement in Splenic immune cells home to injuries
neuroinflammation acts in addition to the central throughout the body
inflammation perpetuated by microglia and other Spleen has the ability to rapidly deploy this cohort of
inflammatory mediators. In summary, injury to the undifferentiated monocytes. [68,70,72] Splenic monocytes
CNS leads to a peripheral and central response that have been shown to exit the spleen and accumulate
act together to cause inflammation, which eventually in the heart after myocardial infarction to participate in
leads to a chronic inflammatory state that causes immunological processes such as wound healing. In
[70]
neural degeneration rather than repair and resolution the context of CNS injury, several aspects of the splenic
after insult. response have been observed. One study has shown
that the number of T cells in the spleen decreases
Although a strong connection between CNS injury and 1-2 days after traumatic brain injury. In a study that
[72]
the immune system has been shown, little research induced middle cerebral artery occlusion (MCAO) on
has been directed at exploring the role of the thymus mice, researchers observed both splenic contraction
in TBI. Recent studies have shown upregulation of and a reduction in the number of splenic cells after
CCL20 in the thymus after TBI. Other studies have stroke was induced. In that same experiment, splenic
[27]
[68]
shown that the liver may play a role in exacerbating contraction coincided with a decrease in monocytes
the neuronal degeneration after TBI (Campbell et al. ). in the spleen, and a concurrent increase in the same
[67]
Depletion of hepatic Kupffer Cells reduced ED-1 subsets of monocytes in the ischemic brain. [68]
positive macrophage and neutrophil migration into
an IL-1β injected brain. As a reservoir of peripheral Spleen and CNS injuries
[67]
immune cells, the spleen has been shown to play a Since research has shown that the immunologic
major role in traumatic brain injury. [28] response to TBI and stroke can in fact exacerbate the
88 Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ May 17, 2017