CHRONIC METABOLIC MEASUREMENTS OF NORMAL BRAIN TISSUE RESPONSE TO PHOTODYNAMIC THERAPY

We tested whether cerebral arteriovenous malformations (AVM) alter brain tissue oxygen pressure, Po2, carbon dioxide pressure Pco2, and pH before, during, and after hypercapnia. A craniotomy was performed and a sensor inserted into normal brain tissue (control) (n = 7) or into tissue adjacent to an AVM (n = 9). Under baseline conditions, tissue Po2 was 80% lower in AVM compared to control patients, but Pco2 and pH were normal. During a 10 mm Hg increase in Paco2, tissue Po2 increased only in AVM patients, Pco2 increased in both groups, and pH decreased only in controls. When hypercapnia was reversed, tissue Pco2 decreased below baseline and pH increased in AVM patients. Results suggest that tissue CO2 washout and elevated pH result from increases in blood flow during hypercapnia. This response may be related to symptoms of hyperperfusion during AVM resection.

Download Full-text

Metabolic and Physiological Responses of Mammary Carcinoma in the Mouse and Normal Brain Tissue in the Rat to Photodynamic Therapy

Magnetic Resonance in Experimental and Clinical Oncology ◽

10.1007/978-1-4613-0691-7_4 ◽

1990 ◽

pp. 95-120 ◽

Cited By ~ 1

Author(s):

M. Chopp ◽

Q. Jiang ◽

Q. Chen ◽

M. Dereski ◽

F. W. Hetzel

Keyword(s):

Photodynamic Therapy ◽

Brain Tissue ◽

Mammary Carcinoma ◽

Physiological Responses ◽

Normal Brain ◽

Normal Brain Tissue

Download Full-text

Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

Scientific Reports ◽

10.1038/s41598-021-84600-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mariano Guardia Clausi ◽

Alexander M. Stessin ◽

Zirun Zhao ◽

Stella E. Tsirka ◽

Samuel Ryu

Keyword(s):

Brain Tissue ◽

Cranial Irradiation ◽

Subcortical White Matter ◽

Glioma Cell Line ◽

Hippocampal Neurogenesis ◽

Normal Brain ◽

Long Term Effects ◽

Normal Brain Tissue ◽

Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

Download Full-text

Quantitative Measurements of Regional Glucose Utilization and Rate of Valine Incorporation into Proteins by Double-Tracer Autoradiography in the Rat Brain Tumor Model

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1989.12 ◽

1989 ◽

Vol 9 (1) ◽

pp. 87-95 ◽

Cited By ~ 22

Author(s):

Michihiro Kirikae ◽

Mirko Diksic ◽

Y. Lucas Yamamoto

Keyword(s):

Protein Synthesis ◽

Brain Tumor ◽

Rat Brain ◽

Brain Tissue ◽

Glucose Utilization ◽

Tumor Model ◽

Normal Brain ◽

Normal Brain Tissue ◽

Rat Brain Tumor ◽

Brain Tumor Model

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.

Download Full-text