Deficits in Japanese word spelling as an initial language symptom of malignant glioma in the left hemisphere.

BACKGROUND: A good performance status at diagnosis is a prognostic factor in patients with malignant glioma whose median survival is 24 months. As early diagnosis may improve their poor prognosis, we looked for currently unknown initial symptoms among patients in good performance status. METHODS: We chose 17 consecutive patients with malignant glioma in the left frontal and/or temporal lobe whose Karnofsky Performance Status was more than 80. At preoperative evaluation, we administered the Japanese version of the Western Aphasia Battery. RESULTS: The chief complaint was difficulty in speech (n = 6), headache/nausea (n = 4), seizures (n = 5), and uncinate fits (n = 1); one patient was symptom-free. Of the 17 patients, 14 exhibited no motor deficits. In 15 patients, the aphasia quotient exceeded 80, indicating that the overall language deficits were mild. However, in the reading section, their scores on the "spelled kanji (Japanese ideogram) recognition" test (full score = 10) were selectively low (5.3 +/- 1.6 for right-handed individuals with frontal lesions, 6.1 +/- 1.0 for right-handed patients with temporal lesions, 7.2 +/- 2.0 for left-handed/bimanual individuals with frontal/temporal lesions). Their scores on the "spelling kanji" test were 3.0 +/- 1.6, 4.8 +/- 1.2, and 9.4 +/- 0.6, respectively. CONCLUSIONS: Our findings point to the importance of recognizing spelling deficits as an initial symptom of left hemisphere glioma in efforts to identify patients in good performance status whose prognosis may be improved. It would be important to determine if the spelling of alphabetic words is also impaired early in the clinical course of left hemisphere glioma.

Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia.

We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased phosphorylation at serine 199/202 and corresponded with an increase in GSK3 phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3 phosphorylate these sites after ischemia. We prepared recombinant normal human tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D-tau40) in which 199/202 serines were changed to alanine by site-directed mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND while N-Tau40 did not. These data suggest that hyperphosphorylation at serine 199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes to ischemic neuronal injury.

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

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.