RRC ID 33272
Author Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M.
Title Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia.
Journal Brain Dev.
Abstract BACKGROUND AND PURPOSE:Most therapeutic agents are administered intravenously (IV) in clinical settings and intraperitoneally (IP) in preclinical studies with neonatal rodents; however, it remains unclear whether intraperitoneal (IP) injection is truly an acceptable alternative for intravenous (IV) injection in preclinical studies. The objective of our study is to clarify the differences in the therapeutic effects of drugs and in the distribution of infused cells after an IP or IV injection in animals with brain injury.
METHODS:Dexamethasone or MK-801, an N-methyl-d-aspartate receptor antagonist was administered either IP or IV in a mouse model of neonatal hypoxic-ischemic encephalopathy. Green fluorescent protein-expressing mesenchymal stem cells (MSCs) or mononuclear cells (MNCs) were injected IP or IV in the mouse model. Two hours and 24h after the administration of the cells, we investigated the cell distributions by immunohistochemical staining. We also investigated distribution of IV administered MNCs labeled with 2-[18F]fluoro-2-deoxy-d-glucose in a juvenile primate, a macaque with stroke 1h after the administration.
RESULTS:IP and IV administration of dexamethasone attenuated the brain injury to a similar degree. IP administration of MK-801 attenuated brain injury, whereas IV administration of MK-801 did not. The IV group showed a significantly greater number of infused cells in the lungs and brains in the MSC cohort and in the spleen, liver, and lung in the MNC cohort compared to the IP group. In the macaque, MNCs were detected in the spleen and liver in large amounts, but not in the brain and lungs.
CONCLUSIONS:This study demonstrated that the administration route influences the effects of drugs and cell distribution. Therefore, a preclinical study may need to be performed using the optimal administration route used in a clinical setting.
Volume 37(4)
Pages 376-86
Published 2015-4
DOI 10.1016/j.braindev.2014.06.010
PII S0387-7604(14)00158-2
PMID 25034178
MeSH Animals Animals, Newborn Bone Marrow Transplantation Brain / drug effects Brain / metabolism Carotid Artery Diseases Dexamethasone / administration & dosage* Dexamethasone / pharmacokinetics Disease Models, Animal Dizocilpine Maleate / administration & dosage* Dizocilpine Maleate / pharmacokinetics Excitatory Amino Acid Antagonists / administration & dosage Excitatory Amino Acid Antagonists / pharmacokinetics Femoral Vein Fluorodeoxyglucose F18 Hypoxia-Ischemia, Brain / drug therapy* Hypoxia-Ischemia, Brain / metabolism Injections, Intraperitoneal Injections, Intravenous Leukocytes, Mononuclear / metabolism Macaca Male Mice Neuroprotective Agents / administration & dosage* Neuroprotective Agents / pharmacokinetics Random Allocation Rats, Inbred Lew Rats, Transgenic Treatment Outcome
IF 1.756
Times Cited 19
Rats LEW-Tg(CAG-EGFP)1Ys(strainID=647)