In vivo MRS study of long-term effects of traumatic intracranial injection of a culture medium in mice

Abstract

Orthotopic transplantation of glioblastoma cells in the brain of laboratory mice is a common animal model for studying brain tumors. It was shown that 1H magnetic resonance spectroscopy (MRS) enables monitoring of the tumor’s occurrence and its development during therapy based on the ratio of several metabolites. However, in studying new approaches to the therapy of glioblastoma in the model of orthotopic xenotransplantation of glioma cells into the brain of mice, it is necessary to understand which metabolites are produced by a growing tumor and which are the result of tumor cells injection along the modeling of the pathology. Currently, there are no data on the dynamic metabolic processes in the brain that occur after the introduction of glioblastoma cells into the brain of mice. In addition, there is a lack of data on the delayed effects of invasive brain damage. Therefore, this study investigates the long-term dyna mics of the neurometabolic profile, assessed using 1H MRS, after intracranial injection of a culture medium used in orthotopic modeling of glioma in mice. Levels of N-acetylaspartate, N-acetylaspartylglutamic acid, myoinositol, taurine, glutathione, the sum of glycerophosphocholine and phosphocholine, glutamic acid (Glu), glutamine (Gln), and gamma aminobutyric acid (GABA) indicate patterns of neurometabolites in the early stage after intracranial injection similar to brain trauma ones. Most of the metabolites, with the exception of Gln, Glu and GABA, returned to their original values on day 28 after injection. A progressive increase in the Glu/Gln and Glu/GABA ratio up to 28 days after surgery potentially indicates an impaired turnover of these metabolites or increased neurotransmission. Thus, the data indicate that the recovery processes are largely completed on day 28 after the traumatic event in the brain tissue, leaving open the question of the neurotransmitter system impairment. Consequently, when using animal models of human glioma, researchers should clearly distinguish between which changes in neurometabolites are a response to the injection of cancer cells into the brain, and which processes may indicate the early development of a brain tumor. It is important to keep this in mind when modeling human glioblastoma in mice and monitoring new treatments. In addition, these results may be important in the development of approaches for non-invasive diagnostics of traumatic brain injury as well as recovery and rehabilitation processes of patients after certain brain surgeries.

Keywords

• magnetic resonance spectroscopy
• animal model of human glioma
• neurometabolites
• traumatic brain injury