Adipose-Derived Mesenchymal Stem Cells and Conditioned Medium Attenuate the Memory Retrieval Impairment During Sepsis in Rats

• DOI: 10.1007/s12035-020-01991-6
• Publication Date: 2020-06-19T23:06:01Z
• Authors: Fariba Akhondzadeh; Mehri Kadkhodaee; Behjat Seifi; Ghorbangol Ashabi; Farzaneh Kianian; Kamal Abdolmohammadi; Maryam Izad; Maryam Adelipour; Mina Ranjbaran
• Keywords: Male; Memory Disorders; 0303 health sciences; Caspase 3; Blood Pressure; Mesenchymal Stem Cells; Punctures; Mesenchymal Stem Cell Transplantation; Hippocampus; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Culture Media, Conditioned; Sepsis; Mental Recall; Animals; Phosphorylation; Rats, Wistar; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cecum; Ligation; Open Field Test; Proto-Oncogene Proteins c-fos

In this study, we hypothesized that sepsis induction impairs memory retrieval in rats while transplanted mesenchymal stem cells (MSCs) and MSC-conditioned medium (MSC-CM) application are capable of attenuating those complications. MSCs were obtained from adipose tissue of rats and at the second culture passage; MSCs and MSC-CM were collected. Rats were randomly divided into four experimental groups: sham, CLP, MSC, and MSC-CM. Sepsis was induced by cecal ligation and puncture (CLP) model in the CLP, MSC, and MSC-CM groups. The MSC group received 1 × 106 MSCs/rat (i.p., 2 h after CLP surgery); the MSC-CM rats received the conditioned medium (CM) from 1 × 106 MSCs intraperitoneally 2 h after sepsis induction. Novel object recognition test, sepsis score, and blood pressure measurement were performed 24 h after the treatments. The right hippocampus was taken for western blot analysis. CLP rats showed a significantly higher sepsis score and systolic blood pressure. They also had a significant increase in the phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and a reduction in c-fos protein in the hippocampus tissue samples compared with the sham group. MSC transplantation and MSC-CM administration significantly decreased the mean sepsis score and prevented sepsis-induced attenuation of blood pressure compared with the CLP rats. Animals in the MSC and MSC-CM groups showed a better memory retrieval, attenuation in phosphorylated form of CAMKII-α, cleaved caspase 3 and Bax/Bcl2 ratio, and an increase in c-fos protein expression compared with the CLP group. It seems that CAMKII and c-fos are inversely involved in regulating memory processes in hippocampus. Phosphorylated form of CaMKII-α overexpression may impair the ability of object recognition. Our findings confirmed that MSC-CM application has more advantages compared with transplanted MSCs and may be offered as a promising therapy for inflammatory diseases such as severe sepsis.