Sensorimotor deficits associated with brain tumor progression and tumor-induced brain plasticity mechanisms.
The objective of this study was to investigate functional deficits and reactive peri-tumoral brain plasticity events in glioma-bearing rats. 9L gliosarcoma cells were implanted into the forelimb region of the sensorimotor cortex in Fischer rats. Control animals underwent the same operation without tumor implantation. Sensitive tests for detecting sensorimotor dysfunction, including forelimb-use asymmetry, somatosensory asymmetry, and vibrissae-evoked forelimb placing tests, were conducted. We found that tumor-bearing animals exhibited significant composite behavioral deficits on day 14 post-tumor injection compared to surgical controls. With the assistance of magnetic resonance imaging, we demonstrated a significant correlation between tumor volume and magnitude of somatosensory asymmetry, indicating that the somatosensory asymmetry test can provide an effective and efficient means to measure and predict tumor progression. Histopathological assessments were performed after the rats were sacrificed 14 days following tumor implantation. Immunostaining revealed that densities of microtubule-associated protein 2, glial fibrillary acid protein, von Willebrand factor, and synaptophysin were all significantly upregulated in the peri-tumoral area, compared to the corresponding region in surgical controls, suggesting synaptic plasticity, astrocyte activation and angiogenesis in response to tumor insult. Understanding the behavioral and bystander cellular events associated with tumor progression may lead to improved evaluation and development of new brain tumor treatments that promote, or at least do not interfere with, functional adaptation.
Yang
Hongyan
H
Institute for Neuroscience and Department of Psychology, University of Texas at Austin, 1 University Station, #A8000, Austin, TX 78712, USA. grace_hyy@mail.utexas.edu
Chopp
Michael
M
Weiland
Barbara
B
Zhang
Xuepeng
X
Tepley
Norman
N
Jiang
Feng
F
Schallert
Timothy
T
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001932:Brain Neoplasms / Q000150:complications* / Q000473:pathology*; D018450:Disease Progression; D005552:Forelimb / Q000502:physiology; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007211:Indoles; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013003:Somatosensory Cortex / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D014738:Vibrissae / Q000294:innervation / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; C514578:synaptopHIuorin; D049452:Green Fluorescent Proteins; C007293:DAPI