TY -

T1 - The meningeal lymphatic system’s role in brain connectivity and

hyperexcitability
SN -
UR - URN:NBN:fi:hulib-202212154167;http://hdl.handle.net/10138/351912
T3 -
A1 - Janutenas, Simas
A2 -
PB - Helsingin yliopisto;University of Helsinki;Helsingfors universitet
Y1 - 2022
LA - eng
AB - Epileptic patients experience spontaneous recurrent seizures and interictal
epileptiform discharges that lead to brain injuries, triggering neuroinflammation
and waste product accumulation. Due to the detrimental effect of waste products on
brain homeostasis, their removal from the central nervous system is (CNS) is
crucial. Meningeal lymphatic vessels (mLVs) located in dura matter contribute to
CNS clearance by the drainage of metabolites, waste products, and immune cells from
subarachnoid space into cervical lymph nodes. Therefore, because of its role in
brain homeostasis, the study of mLVs in different neurological conditions and
diseases, including TLE, has gotten increased attention in the last decade.
In this study, we sought to understand mLVs role in neuroinflammation and changes
in rapid eye movement (REM) sleep stage during epilepsy. For this purpose, we
induced mLVs ablation followed by kainic acid (KA) epilepsy model in mice. Shortly,
animals were inoculated with AAV-VEGFR3-1-4 to induce mLVs ablation and
subsequently challenged with KA to induce status epilepticus. Simultaneously, a
control group of animals were injected with a sham AAV and later injection of KA.
Afterward, spontaneous EEG activity was registered continuously, and data analysed
to compare durations of REM sleep. Also, immunohistochemistry of brain samples was
performed to investigate neuroinflammatory changes between experimental groups.
Ex-vivo analyses of Iba1 and GFAP expression in brain tissue did not show
statistically significant changes in neuroinflammation between experimental groups.
However, we observed a trend towards lower expression of inflammatory markers in
mLVs ablated animals. The analysis of REM sleep duration shows a progressive
reduction of this sleep stage in both groups during the first recording period with
a subsequent stabilization during the second one. Our data also indicate that mLVs
ablated animals present prolonged REM sleep duration compared to the control group.
Although this data contradicts our initial hypothesis it is consistent with the
well-established negative correlation between neuroinflammation and REM sleep
duration. Future studies should consider a deeper analysis of the glial cell
profile for a better understanding of the effect of mLVs dysfunction on epileptic
pathology. Moreover, the impact of mLVs ablation on REM sleep duration should be
characterized in healthy animals.
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KW - meningeal lymphatic vessels;temporal lobe epilepsy;status
epilepticus;EEG;neuroinflammation;REM sleep
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