Local fluorouracil chemotherapy interferes with neural and behavioral recovery after brain tumor-like mass compression.
In this study, we investigated the impact of intracerebral delivery of chemotherapy on functional recovery from focal cortical tissue displacement, characteristic of brain tumors. Unilateral focal brain compression was induced by epidural implantation of an inverted hemisphere-shaped bead over the sensorimotor cortex. Microinjections of a total of 1mg chemoagent fluorouracil or the same volume of saline were made into the compressed cortex. Behavioral tests of forelimb sensorimotor function were conducted during 4 weeks' observation. Rats subjected to any of the three types of lesions, saline microinjection plus cortical compression, chemoagent microinjection alone, or chemoagent microinjection combined with cortical compression, demonstrated significant behavioral deficits in several sensorimotor tasks, compared with saline-microinjected control animals. In placing tests, behavioral deficits elicited by each single treatment were worsened by combined treatment with chemoagent microinjection and focal cortical compression. Concurrently, local delivery of chemoagent into the compressed cortex induced increased cortical tissue loss, necrosis and apoptosis. These data indicate that local chemotherapy exacerbates compression-induced neurological impairment, and a model of controlled focal cortical compression may provide a valuable means to improve anti-cancer therapeutic designs with reduced deterioration of brain function.
Yang
Hongyan
H
Institute for Neuroscience, University of Texas at Austin, 1 University Station, Austin, TX 78712, USA. grace_hyy@mail.utexas.edu
Zhang
Xuepeng
X
Chopp
Michael
M
Jiang
Feng
F
Schallert
Timothy
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology* / Q000523:psychology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005472:Fluorouracil / Q000009:adverse effects*; D005552:Forelimb / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D020287:In Situ Nick-End Labeling; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D016612:Paraffin Embedding; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000187:drug effects / Q000502:physiology; D014738:Vibrissae / Q000502:physiology
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil