- Academic Editor
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Background: White matter injury (WMI) in basal ganglia usually induces
long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel
expressed in microglia and induces neuroinflammation after ICH. Here, we
investigated the functions and roles of Kv1.3 activation-induced inflammatory
response in WMI and the Kv1.3 blockade effect on microglia polarization after
ICH. Methods: Mice ICH model was constructed by autologous
blood injection. The expression of Kv1.3 was measured using immunoblot, real-time
quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays.
Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a
selectively pharmacological Kv1.3 blocker, was investigated using open field test
(OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked
immunosorbent assay (ELISA) were taken to elucidate the expression of
pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1’s function
in regulating microglia polarization was investigated using immunoblot, RT-qPCR,
and immunostaining assays. The downstream PAP-1 signaling pathway was determined
by RT-qPCR and immunoblot. Results: Kv1.3 expression was increased in
microglia around the hematoma significantly after ICH. PAP-1 markedly improved
neurological outcomes and the WMI by reducing pro-inflammatory cytokine
accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1
reduces NF-