Inflammatory changes in the choroid plexus after paclitaxel treatment

Název česky Zánětlivé změny choroidního plexu po léčbě paklitaxelem
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SINAI CACODCAR Rahul Sanjiva SLANÍKOVÁ Adriana LUJC Michael KLUSÁKOVÁ Ilona DUBOVÝ Petr JOUKAL Marek

Rok publikování 2017
Druh Další prezentace na konferencích
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Popis Peripheral neuropathy as a side effect of chemotherapeutic agent Paclitaxel is caused by disorders of calcium homeostasis and mitochondrial damage in axons. These changes are associated with release of damage associated molecular patterns to the blood stream with potential effect on the blood-cerebrospinal fluid (B-CSF) barrier presented in choroid plexus (CP) of the brain ventricles. The aim of our work was to study the cellular and the molecular changes in the CP after intraperitoneal administration of Paclitaxel. Wistar rats (n=23, males) were used in our experiments. Intraperitoneal injection of Paclitaxel in 4 doses with cumulative dose 8 mg/kg was performed in experimental rats while control animals received vehiculum (alcohol and cremophor; 1:1). The animals were left to survive for 1, 3, 7 and 14 days from the last application. Experimental and control rats were sacrificed together with naive rats and perfused transcardially by Zamboni´s fixative. Cryostat coronal sections through the brain were cut and immunostained for activated (ED1) and resident (ED2) macrophages as well as for Toll-like Receptors 9 (TLR-9). Numbers of ED1+ and ED2+ cells per 1 mm2 and intensity of TLR9 immunofluorescence in CP were counted and statistically analyzed. Presence of ED1+ and ED2+ macrophages was observed in epiplexus position of CP. Statistically significant increased numbers of ED1+ and ED2+ macrophages comparing to naive and control rats were found in the CP after administration of Paclitaxel. Number of ED1+ cells increased with time of survival. TLR-9 immunofluorescence was presented in cytoplasm of the cuboidal cells and its immunofluorescence intensity increased with time after the last application. Our results clearly indicate that intraperitoneal administration of Paclitaxel induces inflammatory response in CP expressed by increased numbers of macrophages and expression of TLR-9 following the time from the last application.
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