Brain: Microglia activation and blood-brain barrier permeability in cerebral small vessel disease

Cerebral small vessel disease (SVD) is the main cause of stroke and dementia
.

Little is known about the underlying pathogenesis, but it has been hypothesized that both neuroinflammation and blood-brain barrier permeability play a role, and preclinical studies have shown that these two processes may be related

Blood vessel

Recently, a research paper published in Brain magazine uses DCE-MRI data to evaluate the permeability of the blood-brain barrier, and ¹¹ C-PK11195 PET data to evaluate the activation of microglia
.

The study determined whether there is evidence of increased BBB permeability, especially hotspot areas with increased permeability, and the relationship between these and WMH

Recently, Brain magazine published a research paper, using DCE-MRI data to evaluate the permeability of the blood-brain barrier, and ¹¹ C-PK11195 PET data to evaluate the activation of microglia

Based on PET magnetic resonance, the study used the transporter radioligand ¹¹ C-PK11195 to simultaneously measure microglia activation, and dynamic contrast-enhanced MRI to measure the permeability of the blood-brain barrier
.

The case control was designed for two disease groups with sporadic SVD (n = 20), single-gene SVD (autosomal dominant arterial disease with subcortical infarction and leukoencephalopathy, CADASIL) and a normal control group (n = 20) ) Conducted research

¹¹

Demographics, medical history, SVD conventional MRI markers and PET injection details of the three groups

Demographics, medical history, SVD conventional MRI markers and PET injection details of the three groups

In sporadic SVD , in addition to the increase in average blood-brain barrier permeability (P<0.
001), ¹¹ C-PK11195 binding hot spot volume (P = 0.
003) and blood-brain barrier permeability hot spot volume (P = 0 ) in normal white matter .
) Both increase
.

The volume of ¹¹ C-PK11195 binding hotspot in sporadic SVD normal white matter (P = 0.
003) and the volume of blood-brain barrier permeability hotspot (P = 0.
) both increased the volume of ¹¹ C-PK11195 binding hotspot (P = 0.
) in normal white matter.
= 0.
003) and the blood-brain barrier permeability hot spot volume (P = 0.
) increased by ¹¹

In CADASIL, no increase in the permeability of the blood-brain barrier was found
.

^The increasing trend of ¹¹ C-PK11195 binding was not obvious (P = 0.

^{11 11}

Comparison of the permeability of the blood-brain barrier between the two groups
.

(A) Average BBB permeability (K _i )

Comparison of the permeability of the blood-brain barrier between the two groups

¹¹ C-PK11195 combined with comparison between groups
.

(A) An average of ¹¹ C-PK11195 BPND

¹¹ C-PK11195 combined with comparison between groups

BBB permeability and ¹¹ CPK11195 combined hot spots
.

Example images from four different SVD subject groups (AD) show that the T2 FLAIR image is covered with hot spots of BBB permeability (green) and ¹¹ C-PK11195 binding (yellow)
.

BBB permeability and ¹¹ CPK11195 combined hot spots
.
Example images from four different SVD subject groups (AD) show that the T2 FLAIR image is covered with hot spots of BBB permeability (green) and ¹¹ C-PK11195 binding (yellow)
.
^{11 11}

93 blood biomarkers related to cardiovascular disease, inflammation and endothelial activation were measured for each participant
.
Principal component analysis was performed.
The first component is related to the permeability of the blood-brain barrier and the activation of microglia
.
The hot spots of normal white matter and the average volume of blood-brain barrier permeability values ​​of the sporadic SVD group were all related to dimension 1 (β=0.
829, P=0.
017, β=0.
976, P= 0.
003 ) .
No association with ¹¹ C-PK11195 binding .
No association with blood markers was found in the CADASIL group .
 

The first component of the cardiovascular system is related to the permeability of the blood-brain barrier and the activation of microglia.
The first component is related to the permeability of the blood-brain barrier and the activation of microglia .
The hot spots of normal white matter in the SVD group and the average volume of blood brain The barrier permeability values ​​are all related to dimension 1 (β = 0.
829, P = 0.
017, β = 0.
976, P = sporadic SVD group normal white matter hot spots and average volume of blood-brain barrier permeability values ​​are all related to dimension 1 ( β = 0.
829, P = 0.
017, β = 0.
976, P = 0.
003 ) .
0.
003 ) .
¹¹ 
 

In summary, the results of this study show that in sporadic SVD, both the permeability of the blood-brain barrier and the activation of microglia are increased, but they are spatially different
.
It provides further evidence that these processes may represent therapeutic targets for the disease
.
However, the results of this study prove the correlation, rather than causation, and longitudinal and intervention studies are needed to determine whether these processes promote the progression of white matter damage and clinical symptoms
.
The study also proved that different processes may play an important role in CADASIL, and the increase in blood-brain barrier permeability plays a secondary role, but it did find evidence of increased microglia activation areas in single-gene and sporadic SVD
.

In sporadic SVD, both the permeability of the blood-brain barrier and the activation of microglia are increased, but they are spatially different
.
In sporadic SVD, both the permeability of the blood-brain barrier and the activation of microglia are increased, but they are spatially different
.
These processes may represent the therapeutic target of the disease.
These processes may represent the therapeutic target of the disease.
The single gene and sporadic SVD have an increase in microglia activation area.
Single gene and sporadic SVD have an increase in microglia activation area.

Original source

Walsh J, Tozer DJ, Sari H, et al.
Microglial activation and blood-brain barrier permeability in cerebral small vessel disease [published online ahead of print, 2021 May 17].
  Brain .
2021;awab003.
doi:10.
1093/brain/awab003

Walsh J, Tozer DJ, Sari H, et al.
Microglial activation and blood-brain barrier permeability in cerebral small vessel disease [published online ahead of print, 2021 May 17].
  Brain .
2021;awab003.
doi:10.
1093/brain/awab003 Walsh J, Tozer DJ, Sari H, et al.
Microglial activation and blood-brain barrier permeability in cerebral small vessel disease [published online ahead of print, 2021 May 17].
  Brain .
2021;awab003.
doi:10.
1093/brain/awab003 Brain leave a message here