Effects of Chemotherapy on Neuroinflammation, Neuronal Damage, Neurogenesis, and Behavioral Performance in Bone Marrow Transplantation Recipient Mice

Abstract

As bone marrow transplant (BMT) is gradually applied to the study of central nervous system (CNS) disease, it is needed to investigate the proper dose of chemotherapy to eradicate bone marrow cells while bringing little damage to brain. In the present study, we established a BMT model with varied busulfan and cyclophosphamide (Bu-Cy) dosages. The recipient mice's chimera rate, neuronal death, neuroinflammation, and behavioral functions were all investigated. Chimerism of peripheral blood cells was shown to rise with Bu-Cy treatment doses, with 60.7% in the Bu(20 mg/kg)/Cy(100 mg/kg) group and 93.0% in the Bu(35 mg/kg)/Cy(100 mg/kg) group. Recipients with Bu(35 mg/kg)/Cy(100 mg/kg) therapy had brain injury, increased neuroinflammation, diminished neurogenesis and cognitive abnormalities, whereas animals given a lesser dosage had no such brain damages. Conclusively, considering the chimerism and the possibility to damage brain, we recommend Bu(20 mg/kg)/Cy(100 mg/kg) is the ideal dose in BMT for studying CNS diseases in the C57/BL6 mouse strain.

Keywords: Bone marrow transplantation; Brain damages; Chemotherapy; Chimerism; Cognitive function.