Page 93 - Read Online

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

but research suggests another viable option. Stem suggests that the CNS has its own immune system,
cells were shown to preferentially migrate to the and in addition, the peripheral immune system may
spleen following ischemic stroke, and splenectomies play a role in neuroinflammation. [27-29] As mentioned in
[3]
following stroke or TBI reduced neuronal damage. [23-26] the previous section, the negative outcomes of stroke
This supports the concept of an existing dialogue and TBI are exacerbated by the body’s reaction to
between the local CNS and systemic immune system, the injury. The body’s inflammatory response, which
because the spleen is the primary source of systemic protects against infection, also induces a chronic
inflammation, it has been the focus of investigation in state of deterioration in the CNS, exacerbating the
the “brain-spleen inflammatory coupling” associated neurological deficits caused by the initial injury.
with stroke, TBI, and other neurological disorders.
[18]
Therefore, sequestration of inflammation to the spleen Glia
in order to attenuate chronic neuroinflammation and When talking about the CNS and immunity, it is
improve the efficacy of stem cell therapy provides a important to highlight the role of glia. Glia are non-
promising therapeutic approach to stroke and TBI neuronal cells that maintain homeostasis; two common
treatment. glia are astrocytes and microglia. Astrocytes make up
the blood brain barrier, which separates the CNS from
We have chosen to separate the body’s response into the rest of the body, including the peripheral immune
two categories, central inflammation and peripheral system. To prevent entry of peripheral immune cells and
inflammation, in an attempt to show the peripheral counter otherwise widespread cerebral inflammation,
immune response’s contribution to the cognitive the BBB forms a physical boundary with a specialized
decline following TBI and stroke, and elucidate the microvasculature consisting of endothelial cells
potential for research into novel therapies. By central connected by adherent and tight junctions. This
[30]
inflammation we are referring to the role of resident allows control of cerebral homeostasis via selective
cells of the CNS in inflammation, and by peripheral transport of molecules and cells. When the BBB is
[31]
inflammation we are referring to the contribution of the compromised and microglia are activated, inflammation
systemic immune response to neuroinflammation after of the brain ensues.
traumatic brain injury or stroke.
Microglia
Central source of neuroinflammation Microglias are the innate immune cells of the CNS.
Traditionally, the immune system is thought to be They are cells of myeloid lineage that populate the
non-existent in the CNS. Accumulating evidence now CNS during embryogenesis, and thus act similarly to

Figure 1: Central and peripheral sources of inflammation. Following CNS injury, such as stroke and TBI, the traditional concept entails a
robust inflammatory response within the brain, but equally compelling recent evidence has demonstrated an active inflammatory response,
especially from the spleen, contributing to the progression of the disease. Together with other secondary cell death factors, both central and
peripheral inflammation exacerbate CNS injury. CNS: central nervous system; TBI: traumatic brain injury
Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ May 17, 2017 85