W.R. Zhang
Okayama University
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Featured researches published by W.R. Zhang.
Brain Research | 2000
J.M. Wang; Takeshi Hayashi; W.R. Zhang; Kyoji Sakai; Yoshihiko Shiro; Koji Abe
In order to examine the effect of insulin-like growth factor-1 (IGF-1) on ischemic brain injury, IGF-1 was applied topically on the surface of reperfused rat brain after 60 min of transient middle cerebral artery occlusion (MCAO). In contrast to the cases treated with vehicle, the infarct area was greatly reduced at 24 h of reperfusion by treatment with IGF-1. Terminal deoxynucleotidyl transferase mediated dUTP-biotin in situ nick labeling (TUNEL) staining and immunoreactivity for glycogen synthase kinase 3beta (GSK3beta) were also markedly reduced in the brains with IGF-1 treatment. The present results suggest that the treatment with IGF-1 significantly ameliorates brain injury after transient focal brain ischemia associated with the reduction of TUNEL and GSK3beta stainings.
Stroke | 2005
Shoko Nagotani; Takeshi Hayashi; Keiko Sato; W.R. Zhang; Kentaro Deguchi; Isao Nagano; Mikio Shoji; Koji Abe
Background and Purpose— This study aimed to clarify the effect of statins on spontaneous stroke and to examine the antioxidative effect in artificial transient middle cerebral artery occlusion (tMCAO). Methods— Stroke-prone spontaneous hypertensive rats (SHR-SP) were treated with pitavastatin, atorvastatin, simvastatin, or vehicle for 4 weeks. Physiological parameters, serum lipids, and infarct volumes were examined. The markers for oxidative stresses on lipids and DNA were immunohistochemically detected in vehicle-treated or simvastatin-treated SHR-SP with tMCAO. Results— Atorvastatin and simvastatin decreased infarct volumes, with simvastatin most effective. Simvastatin significantly reduced immunoreactivities for oxidative stress markers for lipids and DNA in neurons after tMCAO. Conclusions— The results suggest that the antioxidative properties of statins may be implicated in their beneficial effects against neuronal damage in cerebral ischemia.
Brain Research | 2002
Nobuhiko Omori; Guang Jin; Feng Li; W.R. Zhang; Shao Jun Wang; Yoshiyuki Hamakawa; Isao Nagano; Yasuhiro Manabe; Mikio Shoji; Koji Abe
A phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor gene that suppresses cell growth, inhibits cell migration, and induces apoptosis. Phosphorylated form of PTEN (p-PTEN) is a key survival factor relating PI3K-Akt pathway and their downstream effectors. A spatiotemporal profiles of PTEN and p-PTEN expression were immunohistochemically examined after 90 min of transient middle cerebral artery occlusion in rats. In the ischemic core, PTEN progressively decreased by 3 days, whereas a rapid but transient increase of p-PTEN was found with a peak at 1 h after the reperfusion. In contrast, in the ischemic penumbra, PTEN showed a minor change and a gradual but sustained p-PTEN expression was observed in the ischemic penumbra with a peak at 12 h. In addition, the balance of population among strongly, moderately, and weakly stained cells was different between the ischemic core and penumbra at their peak time points. These results suggest an important role of p-PTEN for cell survival after ischemia as an upstream regulator for PI3K-Akt.
Neurological Research | 2000
W.R. Zhang; Takeshi Hayashi; H. Kitagawa; Chihoko Sasaki; Kyoji Sakai; Hitoshi Warita; J.M. Wang; Yoshihiko Shiro; M. Uchida; Koji Abe
Abstract It has been empirically known that Ginkgo extract is useful for reducing many symptoms associated with cerebral blood flow (CBF) insufficiency, but its mechanisms have been uncertain. In the present study, therefore, we gave Ginkgo extract to rats with per os digestion, and investigated its effect on CBF and ischemic brain damage with middle cerebral artery occlusion (MCAO). The treatment with Ginkgo extract (W mg 100g-1 rat) increased CBF in the normal condition, but the degree of increase in CBF was lesser during and after MCAO. TTC staining showed that infarct volume was reduced with Ginkgo treatment. TUNEL and HSP72 immunostaining confirmed the protective effect of Ginkgo treatment reducing numbers ofTUNEL and FiSP72 positive cells. Immunohistochemical analysis showed that caspase-3 expression was less abundant in Ginkgo treated rats. The present results suggest that Ginkgo extract contains a substance which increases normal CBF and reduces ischemic brain damage. [Neurol Res 2000; 22: 517-521]
Brain Research | 2002
W.R. Zhang; Keiko Sato; Masanori Iwai; Isao Nagano; Yasuhiro Manabe; Koji Abe
The time dependent influence of adenovirus-mediated glial cell line-derived neurotrophic factor (GDNF) gene (Ad-GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with Ad-GDNF significantly reduced the infarct volume when immediately administered after the reperfusion, but became insignificant when administered at 1 h after the reperfusion as were the cases treated with vehicle- and adenoviral vector containing the E. coli lacZ gene (Ad-LacZ)-treated groups. The protective effect of GDNF was related to the significant reduction of the number of TUNEL positive cells as well as immunohistochemical positive cells for active caspase-3 but not -9. These results showed that exogenous GDNF gene transfer successfully reduced the infarct size in a time-dependant manner by suppressing active caspase-3 but not active caspase-9. However, the therapeutic time window was shorter than the effect of GDNF protein itself previously reported.
Brain Research | 2001
W.R. Zhang; Takeshi Hayashi; Masanori Iwai; Isao Nagano; Keiko Sato; Yasuhiro Manabe; Koji Abe
Time dependent influence of glial cell line-derived neurotrophic factor (GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with GDNF significantly reduced the infarct volume stained with 2,3,5-triphenyltetrazolium chloride (TTC) when GDNF was topically applied at 0 and 1 h of reperfusion, but became insignificant at 3 h as compared to vehicle group. The protective effect of GDNF was closely related to the significant reduction of the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) positive cells as well as immunofluorescently positive cells for active forms of caspases, especially active caspase-3 but not -9. Thus, the present study showed that topical application of GDNF significantly reduced infarct size in a time-dependent manner, while the therapeutic time window was shorter than other chemical compounds such as an NMDA receptor antagonist (MK-801) and a free radical scavenger (alpha-phenyl-tert-butyl-nitrone, PBN). The effect of GDNF was stronger in suppressing active caspase-3 than active caspase-9.
Neuropathology and Applied Neurobiology | 2000
Takeshi Hayashi; Kyoji Sakai; Chihoko Sasaki; W.R. Zhang; Koji Abe
Although mature neurones do not replicate genomic DNA, some cell cycle‐related kinases are aberrantly activated in neurones after ischaemia. As hyper‐phosphorylation of retinoblastoma (Rb) protein is the common pathway in mitotic signal cascade, this study investigated the phosphorylation state of the Rb protein as well as its mRNA level in rat brain after transient middle cerebral artery (MCA) occlusion. Immunohisto‐chemical analysis revealed that neurones in the sham‐operated brain expressed Rb protein without the hyperphosphorylated form. Immunoreactivity for the hyperphosphorylated form of Rb protein progressively increased from 1 h to 3 days after ischaemia in neurones in the MCA territory. Western blot analysis demonstrated a similar change. However, reverse transcription‐polymerase chain reaction study revealed that Rb showed no definite change at the mRNA level. These results suggest that Rb protein is progressively hyper‐phosphorylated in the brain after ischaemia, which may activate apoptotic mechanisms in neuronal cells of the brain after ischaemia.
Brain Research | 1999
W.R. Zhang; H. Kitagawa; Takeshi Hayashi; Chihoko Sasaki; Kyoji Sakai; Hitoshi Warita; Yoshihiko Shiro; H. Suenaga; H. Ohmae; S. Tsuji; T. Itoh; O. Nishimura; H. Nagasaki; Koji Abe
In order to examine the effect of neurotrophin-3 (NT-3) on ischemic brain injury, NT-3 was topically applied to brain surface just after 90 min of middle cerebral artery occlusion (MCAO) in rats. NT-3 significantly reduced the infarct size at 24 h of reperfusion. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick labeling (TUNEL) staining and immunohistochemical study for caspase-3 and heat shock protein 72 (HSP72) showed that NT-3 treatment decreased the number of cells with DNA fragmentation and caspase-3 and HSP72 expressions. These data suggest that NT-3 protects neuronal cells from ischemic injury, and it is possibly associated with inhibition of DNA fragmentation.
Neurological Research | 2001
W.R. Zhang; Takeshi Hayashi; Chihoko Sasaki; Keiko Sato; Isao Nagano; Yasuhiro Manabe; Kouji Abe
Abstract EPC-K1, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl-hydrogen phosphate] potassium salt, is a novel antioxidant. In this study, we investigated a reduction of oxidative neuronal cell damage with EPC-K1 by immunohistochemical analysis for 8-hydroxy-2′-deoxyguanosine (8-OHdG) in rat brain with 60 min transient middle cerebral artery occlusion, in association with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and staining for total and active caspase-3. Treatment with EPC-K1 (20mg kg-1 i.v.) significantly reduced infarct size (p < 0.05) at 24 h of reperfusion. There were no positive cells for 8-OHdG and TUNEL in sham-operated brain, but numerous cells became positive for 8-OHdG, TUNEL and caspase-3 in the brains with ischemia. The number was markedly reduced in the EPC-K1 treated group. These reductions were particularly evident in the border zone of the infarct area, but the degree of reduction was less in caspase-3 staining than in 8-OHdG and TUNEL stainings. These results indicate EPC-K1 attenuates oxidative neuronal cell damage and prevents neuronal cell death. [Neurol Res 2001; 23: 676-680]
Acta neurochirurgica | 2003
Keiko Sato; Masanori Iwai; W.R. Zhang; Hiroshi Kamada; K. Ohta; Nobuhiko Omori; Isao Nagano; Mikio Shoji; Koji Abe
The highly polysialylated neural cell adhesion molecule (PSA-NCAM) is involved in migration of neural stem cells as well as in neural plasticity. Immunoreactive PSA-NCAM expression was examined in rats with repeated exposure to amygdaloid kindled generalized seizures (GS). The number of PSA-NCAM positive cells in the bilateral dentate gyrus (DG) increased significantly from GS. Although the total number of positive cells was not significantly different between animals with 3 times GS (3 GS) and 30 times GS (30 GS), in the latter group a greater number of positive cells was observed in the outer granule cell layer (GCL) and a marked extension of immunopositive dendrites to the molecular layer. These observations indicate that increased migration of newly generated cells as well as plastic changes of preexisting neural cells occur in response to recurrent GS. This may contribute to an abnormal reconstruction of the synaptic network in the hippocampus and, thus, epileptogenicity from kindling.