Development and plasticity of meningeal lymphatic vessels
Résumé
The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS.
Mots clés
interstitial fluid
JV
jugular vein
LEC
lymphatic EC
LV
lymphatic vessel
MMA
middle meningeal artery
PFA
paraformaldehyde
PPA
pterygopalatine artery
RRV
rostral rhinal vein
RT
room temperature
SAS
subarachnoid space
SMC
smooth muscle cell
SS
sigmoid sinus
SSS
superior sagittal sinus
TS
αSMA
α smooth muscle actin BBB
blood-brain barrier BV
blood vessel CM
cisterna magna CN
cranial nerve CNS
central nervous system COS
confluence of sinuses CSF
cerebrospinal fluid dcLN
deep cervical LN EB
Evans blue EC
endothelial cell EdU
5-ethynyl-2-dioxyuridine FM
foramen magnum i.c.m.
intracisternal(ly) i.c.v.
intracerebroventricular(ly) i.g.
intragastric(ally) ISF
interstitial fluid JV
jugular vein LEC
lymphatic EC LV
lymphatic vessel MMA
middle meningeal artery PFA
paraformaldehyde PPA
pterygopalatine artery RRV
rostral rhinal vein RT
room temperature SAS
subarachnoid space SMC
smooth muscle cell SS
sigmoid sinus SSS
superior sagittal sinus TS
transverse sinus
α smooth muscle actin
BBB
blood-brain barrier
BV
blood vessel
CM
cisterna magna
CN
cranial nerve
CNS
central nervous system
COS
confluence of sinuses
CSF
cerebrospinal fluid
dcLN
deep cervical LN
EB
Evans blue
EC
endothelial cell
EdU
5-ethynyl-2-dioxyuridine
FM
foramen magnum
i.c.m.
intracisternal(ly)
i.c.v.
intracerebroventricular(ly)
i.g.
intragastric(ally)
ISF
Domaines
Médecine humaine et pathologieOrigine | Publication financée par une institution |
---|---|
Licence |