Sodium orthovanadate enhances proliferation of progenitor cells in the adult rat subventricular zone after focal cerebral ischemia

Jun Matsumoto, Motohiro Morioka, Yu Hasegawa, Takayuki Kawano, Yutaka Yoshinaga, Tatsumi Maeda, Shigetoshi Yano, Yutaka Kai, Kohji Fukunaga, Jun Ichi Kuratsu

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Neuronal progenitor cells able to produce new neuron and glia persist in the adult central nervous system (CNS). Their proliferation is up-regulated by growth factors or cytokines under some pathological conditions, including ischemia. Because sodium orthovanadate (SOV), a protein tyrosine phosphatase inhibitor, can up-regulate tyrosine kinase-linked growth factor receptor signaling via the inhibition of tyrosine residue dephosphorylation, it may be capable of enhancing progenitor cells. To investigate the effect of SOV on progenitor cells in the subventricular zone (SVZ), we injected rats intraperitoneally with 50 mg/kg bromodeoxyuridine (BrdU) and 12.5 or 25 mM SOV or BrdU and saline (control) on days 1 to 7 after middle cerebral artery occlusion. The density of BrdU-positive cells in the ipsilateral SVZ showed a significant SOV dose-dependent increase. This effect was found only in the ipsilateral and not contralateral SVZ, and it was not found in nonischemic rats. Double immunolabeling with BrdU and double cortin, a marker of migrating neuroblast, revealed that the density of double-positive cells increased significantly in an SOV dose-dependent manner. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining suggested that the SOV-induced increase was not due to antiapoptotic effects. Treatment with SOV also significantly increased the density of cells positive for BrdU and phosphorylated Akt and BrdU and phosphorylated extracellular signal-regulated kinase (ERK). We postulate that ischemia triggers off the proliferation of SVZ cells by bioactive factors such as growth factors and that SOV enhances the proliferation of only triggered-off SVZ cells with Akt and ERK activation. Our findings suggest that SOV may aid in the self-repair of the postischemic CNS.

Original languageEnglish
Pages (from-to)982-991
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume318
Issue number3
DOIs
Publication statusPublished - 2006 Aug 28

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Sodium orthovanadate enhances proliferation of progenitor cells in the adult rat subventricular zone after focal cerebral ischemia'. Together they form a unique fingerprint.

Cite this