Characterization of the subventricular zone neurogenic response to rat malignant brain tumors.
The subventricular zone (SVZ) is one of the neurogenic regions of the adult brain. We characterized the neurogenic response of the SVZ to the growth of brain tumors in the rat striatum. Abundant nestin positive cells, most likely representing reactive astrocytes, were found surrounding the tumor. However, we observed no substantial migration of nestin positive cells from the SVZ toward the tumor. Tumor growth resulted in decreased numbers of bromodeoxyuridine positive and Ki-67 positive proliferating cells and a concomitant increase in doublecortin and polysialylated neural cell adhesion molecule immunoreactivity within the SVZ. Neuroblasts were observed in high numbers in the area between the SVZ and the tumor, most likely pointing to the SVZ as the principal source of these cells. Neuroblasts located between the SVZ and the tumor expressed the transcription factor Pbx, a marker for immature striatal neurons. However, no evidence of neuroblast differentiation into fully mature neurons was found. This study thus demonstrates increased neuroblast immunoreactivity within the SVZ ipsilateral to a brain tumor in the striatum. SVZ-derived neuroblasts attracted by the tumor adopt an immature striatal phenotype indicating a region specific reparative mechanism in response to a malignant tumor.
Bexell
D
D
The Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Lund, Sweden. daniel.bexell@med.lu.se
Gunnarsson
S
S
Nordquist
J
J
Bengzon
J
J
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000379:methods; D002552:Cerebral Ventricles / Q000473:pathology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005910:Glioma / Q000473:pathology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012794:Sialic Acids / Q000378:metabolism; D013997:Time Factors
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D009479:Neuropeptides; D012794:Sialic Acids; C413663:fluorescent protein 583; C103469:polysialyl neural cell adhesion molecule; D001973:Bromodeoxyuridine