Poster Session B   |   7:00am Expo - Hall A & C   |   Poster ID #425

Histological Analysis of White Matter Disruption in a Glioma Xenograft Model

Program:
Academic Research
Category:
Tumor Biology
FDA Status:
Not Applicable
CPRIT Grant:
Cancer Site(s):
Brain and Nervous System
Authors:
Christopher File
The University of Texas Medical Branch at Galveston
Alfredo Sandoval
The University of Texas Medical Branch at Galveston
Abbigael Aday
The University of Texas Medical Branch at Galveston
Sean O'Leary
The University of Texas Medical Branch at Galveston
Alvin LeBlanc
The University of Texas Medical Branch at Galveston
Pablo Valdes-Quevedo
The University of Texas Medical Branch at Galveston

Introduction

Gliomas, central nervous system neoplasms originating from glial cells, present significant challenges to surgical treatment due to their complex interaction with brain parenchyma. The first-line treatment, surgical excision, necessitates careful navigation to avoid critical brain structures, underscoring the importance of precise preoperative mapping.

Diffusion Tensor Imaging (DTI) is commonly employed for this purpose, providing surgeons with invaluable information about surrounding white matter tracts (WMTs) and aiding in refining surgical approaches. However, DTI has limitations, particularly in visualizing tumor infiltration into WMTs and mapping around tumor-induced edema, both prevalent in gliomas. Consequently, a more detailed classification of changes in the tumor environment, including WMT displacement and impingement, is a crucial step towards improving preoperative WMT identification.

In this study, we aim to enhance the classification of WMT structural alterations associated with human glioma pathogenesis. To achieve this, we utilize a mouse glioma model, providing a controlled environment to study these complex interactions and contribute to the ongoing efforts to improve surgical outcomes in glioma treatment.

Methods

We created a mouse glioma model via injecting U87 line human glioblastoma cells into an athymic mice to mimic human glioma pathogenesis.
Mice were sacrificed at 14 days following glioma cell implantation. Their brains were imbedded in OCT and frozen overnight. Mouse brains were then cryosectioned into 10-um sections and immunohistochemistry was performed utilizing the following antibodies:
Anti-Glial Fibrillary Acidic Protein (GFAP)
Anti-Myelin Basic Protein (MBP)
4′,6-diamidino-2-phenylindole (DAPI) was used for counterstaining to identify nuclei.

Pictures are collected utilizing Olympus IX71 fluorescent microscope.

Results

PICTURE: IHC staining of a normal mouse cortex. GFAP is represented in red, while blue represents DAPI staining. There is a high prevalence of GFAP-positive cells in the mouse corpus callosum. PICTURE: Coronal section of mouse glioma model using a non-magnified PCO camware. Bright indicates PpIx at 628 nm fluorescence, highly expressed due to 5-ALA-induced accumulation in the tumor. PICTURE: IHC staining of normal mouse cortex. GFAP is represented in red, while blue represents DAPI staining. There is a high prevalence of GFAP-positive cells in the mouse corpus callosum. PICTURE: Image of normal, non-tumor MBP staining at the same anatomical location. Continuous WMTs can be observed. PICTURE: Image of glioma model MBP staining. Large lesions can be seen at the cingulate of the corpus callosum. PICTURE: Combined IHC staining of normal WMT. Represented in green is the immunohistochemical staining of MBP, found in myelin. Red represents GFAP, commonly found in glial cells. Blue represents DAPI, a stain for nuclei. PICTURE: Combined IHC staining of the suspected tumor. Represented in green is the immunohistochemical staining of MBP, found in myelin. Red represents GFAP, commonly found in glial cells. Blue represents DAPI, a stain for nuclei.

Conclusion

Classifying WMTs post-glioma is an ongoing but important effort, as identifying changes can provide insight into the neurosurgical approach.
This study provides a histological characterization of WMTs post-gliomas, where a proportionally small glioma can alter the alignment of WMTs and complicate its excision. Due to time restrictions, quantification of immunofluorescence and general histological staining (H&E, Luxol) could not occur. These would be important elements for future characterization and better identification of WMT abnormalities during glioma.

Further studies can analyze the alterations of humans with glioma WMTs for better pre-surgical planning, as well as improve intraoperative visualization of WMTs.