Stroke: After cerebral hemorrhage, inflammation and anti-inflammatory processes occur at the same time

Spontaneous intracerebral hemorrhage (sICH) is the most common form of hemorrhagic stroke, with poor prognosis and limited treatment options
.
Hemorrhage causes primary brain damage due to mass effect and physical destruction of brain parenchyma

Microglia are part of the innate immune system and provide a stable microenvironment for the functions of the central nervous system
.
After ICH, cytokines and other cytotoxic mediators attract and activate microglia

In the well-characterized tissues of sICH cases, the activation of microglia-macrophages around the hematoma was greatly increased by using a pan-selective marker (Iba1)
.

This raises two questions:
First, do these immune cells have neuroinflammation or anti-inflammatory ingredients?
Second, do blood-borne macrophages contribute to this immune response?

Both of these issues have an impact on treatment.
The first issue is the development of drugs that manipulate the function of microglia, and the second issue is the possible way to deliver therapeutic drugs to the brain tissue

In this way, Anan Shtaya and others at the University of Southampton in the United Kingdom used specific microglial macrophage markers for pro-inflammatory (CD68 and TMEM119) and anti-inflammatory cells (CD163 and CD206) to explore the effects of supratentorial cerebral hemorrhage.
Brain tissue of subjects who died within 0 to 12 days

Finally, the blood inflammatory markers (CRP [C reactive protein], white blood cell and monocyte counts) of prospective sICH patients in a similar time frame were compared
.

Method

In 27 ICH cases (n=27, age: 59[52-80.
5], 14F/13M), all microglia-macrophage markers increased after sICH compared to the control brain

Anti-inflammatory markers (CD163 and CD206) and pro-inflammatory markers (CD68 and TMEM119) increased at the same time
.
CD163 gradually increased after SICH (15.
0-fold increase in 7-12 days, P<0.
001)

CD206 increased at 3 to 5 days (5.

In a prospective cohort of sICH patients (n=26, age 74[66-79], National Institutes of Health Stroke Scale at admission : 8[4-17]; 14F/12M) blood CRP concentration and monocytes Density (but not white blood cells) increases after sICH
.

CRP increased from 0 to 2 days to 3 to 5 days (8.
3 times, P=0.
020), and then decreased in 7 to 12 days
.
Monocytes increased from 0 to 2 days to 3 to 5 days (1.
8 times, P<0.
001), and then decreased in 7 to 12 days
.

The important significance of this research lies in the discovery: a new anti-inflammatory pathway: local microglia and monocytes in the blood occur simultaneously with neuroinflammation after SICH
.
This approach provides a therapeutic goal and window of opportunity (3-5 days after SICH), that is, the invading monocytes can provide therapeutic drugs
.

Original source:
Shtaya A, Bridges LR, Williams R, et al.
Innate Immune Anti-Inflammatory Response in Human Spontaneous Intracerebral Hemorrhage.
Stroke.
Published online July 20, 2021.
doi:10.
1161/STROKEAHA.
121.
034673