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ABSTRACT: To evaluate the safety and efficacy of hypofractionated radiotherapy (RT) with a standard temozolomide (TMZ) regimen for adults with newly diagnosed glioblastoma multiforme (GBM), twenty-six consecutive adults (range 39-79 years) who met our enrollment criteria received short courses of hypofractionated RT (45 Gy in 15 fractions over three weeks) with concomitant TMZ at 75 mg/m(2)/d. After 28 days, TMZ was maintained at 150-200 mg/m(2)/d on five days for 12 cycles or until tumor progression or unacceptable toxicity. The primary end point was determined by overall survival (OS) and toxicity. Secondary assessed end points were: progression-free survival (PFS) at six months, health-related quality of life (HRQOL), and pseudo-progression. We assessed HRQOL by use of the Karnofsky performance status (KPS) and the Functional Assessment of Cancer Therapy-Brain (FACT-Br) Subscale. All 26 patients were evaluated for OS, PFS, and HRQOL. At a median follow-up of 20 months, the median OS was 15.6 months (95% confidence interval 9.0-22.2 months) with acceptable toxicity. PFS rate at six months was 65%. KPS and FACT-Br Subscale scores did not decline after this procedure. Pseudo-progression occurred in two (8%) patients. Adult patients with GBM benefitted from favorable OS and PFS rate as a result of the hypofractionated RT with TMZ. An additional advantage is that this procedure may reduce the course of treatment. Further studies using this procedure are warranted.
Journal of Neuro-Oncology 04/2011; 102(2):247-53. · 3.21 Impact Factor
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ABSTRACT: Chemokines are 8- to 12-kDa peptides that function as chemoattractant cytokines involved in cell activation, differentiation, and trafficking. Chemokines bind to specific G-protein-coupled, seven-span transmembrane receptors on the plasma membrane of target cells. Chemokine (C-X-C motif) ligand 12 (CXCL12), an alpha-chemokine that binds to G-protein-coupled chemokine (C-X-C motif) receptor 4 (CXCR4), plays an important and unique role in the regulation of stem/progenitor-cell trafficking. As CXCR4 is expressed on several cancer cells, these CXCR4-positive cancer cells may metastasize to organs that secrete/express CXCL12. Regarding brain tumors, recent data demonstrate that glioma tumor stem-like cells promote tumor angiogenesis and vasculogenesis via the CXCL12/CXCR4 pathway. In addition, CXCL12/CXCR4 have recently been shown to be expressed in primary central nervous system (PCNS) lymphomas, and a role for chemokines in the pathogenesis of PCNS lymphomas was suggested. This review focuses on current knowledge regarding the biology of the CXCL12/CXCR4 pathway in the context of understanding their potential role in malignant gliomas and PCNS lymphoma development. The CXCL12/CXCR4 interaction as a therapeutic target for malignant brain tumors is also discussed.
Brain Tumor Pathology 01/2011; 28(2):89-97. · 1.19 Impact Factor
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Kiyoshi Kikuchi,
Ko-Ichi Kawahara,
Hisaaki Uchikado,
Naohisa Miyagi,
Terukazu Kuramoto,
Tomoya Miyagi,
Yoko Morimoto,
Takashi Ito,
Salunya Tancharoen,
Naoki Miura, [......],
Yoshihiro Yoshida,
Shinihiro Arimura,
Kentaro Mera,
Ko-Ichi Tada,
Narimasa Yoshinaga,
Ryuichi Maenosono,
Yoshiko Ohno,
Teruto Hashiguchi,
Ikuro Maruyama, Minoru Shigemori
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ABSTRACT: Edaravone was originally developed as a potent free radical scavenger and has been widely used to treat cerebral infarction in Japan since 2001. Several free radical scavengers have been developed and some of them have progressed to clinical trials for the treatment of cerebral infarction. One such scavenger, edaravone, has been approved by the regulatory authority in Japan for the treatment of patients with cerebral infarction. Of particular interest is the ability of edaravone to diffuse into the central nervous system in various neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone has been found to have beneficial effects on inflammation, matrix metalloproteinases, nitric oxide production and apoptotic cell death. Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. The proven safety of edaravone following 9 years of use as a free radical scavenger suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.
Experimental and therapeutic medicine 01/2011; 2(5):771-775.
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ABSTRACT: Effects of edaravone, a free radical scavenger, on post-traumatic impairment of long-term potentiation (LTP) were examined in granule cell layers of the dentate gyrus (DG) in vitro. Field EPSPs (fEPSPs) evoked by stimulation of the perforant path (PP) were recorded extracellularly in the DG one week after a moderate impact applied by a fluid percussion injury (FPI) device. High frequency stimulation (HFS) of the PP caused LTP of the fEPSP-slope in slices from naïve and sham-operated rats, however, the LTP was strongly depressed in slices from FPI rats. Intraperitoneal administration of edaravone 15 min after FPI prevented the hyperactivities of DG neurons and attenuated impairment of the LTP in FPI rat dentate granular cells. In vitro application of spermine NONOate (sp-NO), a nitric oxide (NO) donor, for 30 min produced a gradual increase in the fEPSP-slope, lasting for more than 2 h. Edaravone attenuated the enhancement of the fEPSP-slope induced by sp-NO. After sp-NO treatment HFS could not produce an obvious LTP in the DG granule cell layer. Pretreatment of DG slices with edaravone prevented the sp-NO-induced impairment of LTP. These results suggest that administration of edaravone after FPI protects against post-traumatic impairment of LTP in granule cell layers of the DG, possibly by scavenging NO-related radicals.
The Kurume Medical Journal 01/2011; 58(2):47-58.
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Kiyoshi Kikuchi,
Ko-ichi Kawahara,
Naohisa Miyagi,
Hisaaki Uchikado,
Terukazu Kuramoto,
Yoko Morimoto,
Salunya Tancharoen,
Naoki Miura,
Kazunori Takenouchi,
Yoko Oyama, [......],
Yoshihiro Yoshida,
Shinichiro Arimura,
Kentaro Mera,
Ko-ichi Tada,
Narimasa Yoshinaga,
Ryuichi Maenosono,
Yoshiko Ohno,
Teruto Hashiguchi,
Ikuro Maruyama, Minoru Shigemori
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ABSTRACT: Acute stroke, including acute ischemic stroke (AIS) and acute hemorrhagic stroke, (AHS) is a common medical problem with particular relevance to the demographic changes in industrialized societies. In recent years, treatments for AIS have emerged, including thrombolysis with tissue plasminogen activator (t-PA). Although t-PA is the most effective currently available therapy, it is limited by a narrow therapeutic time window and side effects, and only 3% of all AIS patients receive thrombolysis. Edaravone was originally developed as a potent free radical scavenger and, since 2001, has been widely used to treat AIS in Japan. It was shown that edaravone extended the narrow therapeutic time window of t-PA in rats. The therapeutic time window is very important for the treatment of AIS, and early edaravone treatment is more effective. Thus, more AIS patients might be rescued by administering edaravone with t-PA. Meanwhile, edaravone attenuates AHS-induced brain edema, neurologic deficits and oxidative injury in rats. Although edaravone treatment is currently only indicated for AIS, it does offer neuroprotective effects against AHS in rats. Therefore, we hypothesize that early administration of edaravone can rescue AHS patients as well as AIS patients. Taken together, our findings suggest that edaravone should be immediately administered on suspicion of acute stroke, including AIS and AHS.
Medical Hypotheses 12/2010; 75(6):583-5. · 1.39 Impact Factor
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ABSTRACT: Colors are thought to elicit various emotional effects. Red, with its high likelihood of attracting attention, is considered to have an exciting, active effect; whereas green, with its low attention value, is considered to have a relaxing, sedative effect. Colors are also thought to affect human cognition and emotion. However, there have been few studies of the influence of colors in one's surroundings (e.g., the color environment and its effect on cognitive function). In this study, we investigated the influence of differences in color environments (red, green, or darkness) on cognitive function by analyzing the P300 component of event-related potentials (ERPs) elicited by oddball visual paradigms as a measure of cognitive characteristics in patients who had sustained traumatic brain injury (TBI). In 18 patients with TBI and 18 age-matched control subjects, ERPs were recorded in response to photographs of crying babies. We found that P300 amplitudes in the red environment were significantly larger in controls than in TBI patients, while those in both the green environment and darkness showed no difference between controls and patients. P300 latencies in the red environment and in darkness were significantly longer in patients than in controls. P300 latency in the red environment was significantly shorter than that in darkness. However, P300 latency in the green environment showed no difference between controls and patients. In healthy individuals, the emotional effects of the red environment enhanced cognitive function. In patients with TBI, however, cognitive function was reduced in the red environment. Furthermore, P300 amplitude and latency were strongly correlated with the time on the Trail Making Test (TMT), and the value of the intelligence quotient of the Wechsler Adult Intelligence Scale-III (WAIS-III). These findings suggest that P300 amplitude and latency are useful indexes for the evaluation of TBI patients, and that color environments affect cognitive function.
Journal of neurotrauma 09/2010; 27(9):1577-84. · 4.25 Impact Factor
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ABSTRACT: Epstein-Barr virus (EBV) has been implicated in the pathogenesis of primary central nervous system lymphomas (PCNLs) in immunocompetent hosts. To investigate the role of EBV in the pathogenesis of PCNLs in immunocompetent hosts, this study assessed six PCNL cases (elderly male immunocompetent patients; age ≥60 years) histologically and immunohistochemically, and an EBV genetic study was performed. Histologically, all cases were diagnosed as diffuse large B-cell lymphoma with extensive necrosis. In all six cases, PCNL cells showed immunohistochemical positivity for latent membrane protein 1 (LMP-1) and Epstein-Barr nuclear 2 (EBNA2). Lymphoma cells also showed positive signals for EBV-encoded small RNAs (EBERs) on in-situ hybridization. EBV subtyping-PCR analysis demonstrated that one case was EBNA 2B type and the other five cases were EBNA 2A type, and two cases were EBV wild-type and four cases showed 30-bp LMP-1 deletion by PCR analysis. It is therefore possible that LMP gene deletion or EBNA-2 strain type are important in the tumorigenesis of EBV-positive PCNLs. In addition, EBV-positive PCNLs in immunocompetent hosts may be related to immunological deterioration derived from the aging process.
Journal of Neuro-Oncology 05/2010; 100(2):271-9. · 3.21 Impact Factor
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ABSTRACT: The central nervous system in the embryo develops around the cerebrospinal fluid (CSF), which regulates cell proliferation and differentiation. Neurogenesis has been also reported in the subventricular zone (SVZ), which is close to CSF, after stroke in rats. In this study, CSF extracted following stroke in rats was added to bone marrow stromal cell (MSC) culture in vitro, and the proliferation and differentiation of MSCs were studied. Primary cultures of MSCs were obtained from 7-week-old Lewis rats and incubated in a plastic tissue culture flask. CSF was retrieved from other rats 48 hrs after 0, 15 and 75 min after middle cerebral artery occlusion (MCAO). CSF from these three groups were added to respective MSC culture solutions, and the cells were then incubated for 72 hrs. Western blots of the extracellular signal-regulated kinase-1 and -2 (Erk1/2) were obtained just after the CSF induction. The expressions of CD34, CD45, CD90 and CD108 were assessed by flow cytometric analysis. The proliferation of MSCs was accelerated by the addition of post-stroke CSF, especially in the 15-min MCAO, in a dose-dependent manner. The morphology and surface antigens of the cells were maintained in all groups. Phosphorylated-Erk1/2 was elevated in all the CSF-treated groups, although this effect was more enhanced in the 15-min MCAO group. Our data indicate that the addition of post-stroke CSF to the primary medium stimulated the proliferation of MSCs, and that these MSCs maintained their characteristics through the p-Erk1/2 pathway. These results suggest that use of post-stroke CSF as a component of culture media could facilitate the autologous transplantation of MSCs.
The Kurume Medical Journal 01/2010; 57(1-2):21-8.
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Kiyoshi Kikuchi,
Ko-Ichi Kawahara,
Kamal Krishna Biswas,
Takashi Ito,
Salunya Tancharoen,
Naoto Shiomi,
Yoshiro Koda,
Fumiyo Matsuda,
Yoko Morimoto,
Yoko Oyama, [......],
Yoshiko Ohno,
Ryuichi Maenosono,
Yutaka Tajima,
Hisaaki Uchikado,
Terukazu Kuramoto,
Kenji Nakayama, Minoru Shigemori,
Yoshihiro Yoshida,
Teruto Hashiguchi,
Ikuro Maruyama
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ABSTRACT: Estimation of the postmortem interval (PMI) is one of the most important tasks in forensic medicine. Numerous methods have been proposed for the determination of the time since death by chemical means. High mobility group box-1 (HMGB1), a nonhistone DNA-binding protein is released by eukaryotic cells upon necrosis. Postmortem serum levels of HMGB1 of 90 male Wistar rats stored at 4, 14 and 24°C since death were measured by enzyme-linked immunosorbent assay. The serum HMGB1 level showed a time-dependent increase up to seven days at 4°C. At 14°C, the HMGB1 level peaked at day 3, decreased at day 4, and then plateaued. At 24°C, the HMGB1 level peaked at day 2, decreased at day 3, and then plateaued. Our findings suggest that HMGB1 is related to the PMI in rats.
Experimental and therapeutic medicine 01/2010; 1(1):109-111.
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Kiyoshi Kikuchi,
Salunya Tancharoen,
Fumiyo Matsuda,
Kamal Krishna Biswas,
Takashi Ito,
Yoko Morimoto,
Yoko Oyama,
Kazunori Takenouchi,
Naoki Miura,
Noboru Arimura, [......],
Ryuichi Maenosono,
Yutaka Tajima,
Hisaaki Uchikado,
Terukazu Kuramoto,
Kenji Nakayama, Minoru Shigemori,
Yoshihiro Yoshida,
Teruto Hashiguchi,
Ikuro Maruyama,
Ko-Ichi Kawahara
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ABSTRACT: Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.
Biochemical and Biophysical Research Communications 10/2009; 390(4):1121-5. · 2.48 Impact Factor
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Neuropathology 09/2009; 30(1):97-100. · 2.02 Impact Factor
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Kiyoshi Kikuchi,
Ko-ichi Kawahara,
Kamal Krishna Biswas,
Takashi Ito,
Salunya Tancharoen,
Yoko Morimoto,
Fumiyo Matsuda,
Yoko Oyama,
Kazunori Takenouchi,
Naoki Miura, [......],
Yoshiko Ohno,
Ryuichi Maenosono,
Yoshihiro Yoshida,
Yutaka Tajima,
Hisaaki Uchikado,
Terukazu Kuramoto,
Kenji Nakayama, Minoru Shigemori,
Teruto Hashiguchi,
Ikuro Maruyama
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ABSTRACT: High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death in a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.
Biochemical and Biophysical Research Communications 05/2009; 385(2):132-6. · 2.48 Impact Factor
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ABSTRACT: CXCL12, an alpha-chemokine that binds to G-protein-coupled CXCR4, plays an important and unique role in the regulation of stem/progenitor cell trafficking. To elucidate the correlation between the CXCR4/CXCL12 axis and glioblastomas (GBs), the present study assessed CXCR4/CXCL12 expression in 44 astrocytic tumor tissues using immunohistochemical analyses. Several cell lines of brain tumors were also analyzed by RT-PCR analyses. Although low-grade, astrocytic tumors were rarely positive for CXCL12 immunohistochemically, all GBs showed moderate to intense immunostaining with CXCL12, with particularly intense immunostaining being observed in the pseudopalisading cells and the proliferating microvessels. Regarding CXCR4, widespread positive immunoreactivity was noted in the tumor cells in almost all cases of GBs. In contrast, RT-PCR analysis showed low expression of CXCR4/CXCL12 in the aerophilic condition of GB cells and high expression of CXCR4/CXCL12 in the hypoxic condition of GB cells. Taken together, these results suggest that secretion of CXCR4/CXCL12 by hypoxic pseudopalisading and proliferating microvascular cells contributes to an outward migration of tumor cells away from hypoxia, creating a peripherally moving wave and subsequent microvascular proliferation. Pseudopalisades and proliferating microvessels are also considered to be associated with accelerated growth in GBs. These results indicate that expression of CXCL12 is an accelerated growth factor in GBs.
International Journal of Oncology 04/2009; 34(3):665-72. · 2.40 Impact Factor
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Kiyoshi Kikuchi,
Ko-ichi Kawahara,
Salunya Tancharoen,
Fumiyo Matsuda,
Yoko Morimoto,
Takashi Ito,
Kamal Krishna Biswas,
Kazunori Takenouchi,
Naoki Miura,
Yoko Oyama,
Yuko Nawa,
Noboru Arimura,
Masahiro Iwata,
Yutaka Tajima,
Terukazu Kuramoto,
Kenji Nakayama, Minoru Shigemori,
Yoshihiro Yoshida,
Teruto Hashiguchi,
Ikuro Maruyama
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ABSTRACT: Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 +/- 10.4 and 43.8 +/- 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 microM) suppressed OGD- and H(2)O(2)-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 microM) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.
Journal of Pharmacology and Experimental Therapeutics 04/2009; 329(3):865-74. · 3.83 Impact Factor
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ABSTRACT: A 15-year-old girl presented with a distal anterior inferior cerebellar artery (AICA) dissecting aneurysm manifesting as sudden onset of general tonic-clonic convulsion while singing a song. Physical and neurological examinations found headache, vomiting, right perceptive deafness, and right cerebellar ataxia. Cranial magnetic resonance imaging demonstrated a hemorrhagic mass in the brainstem region, and digital subtraction angiography revealed a fusiform dilatation of the anterior pontine segment of the right AICA. The diagnosis was dissecting aneurysm. Endovascular embolization was performed for aneurysm and parent artery occlusion using a Guglielmi detachable coil and 9 TruFill detachable coil systems, respectively, 2 weeks after occipital artery-AICA anastomosis. No ischemic complications were seen, and her neurological deficits completely recovered after the interventional therapy.
Neurologia medico-chirurgica 03/2009; 49(2):81-4. · 0.61 Impact Factor
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ABSTRACT: From 1994, we have used therapeutic hypothermia in patients with severe traumatic brain injury (Glasgow Coma Scale scores of 5 or less). In 2000, we altered the target temperature to 35 degrees C from the former 33 degrees C, as our findings suggested that cooling to 35 degrees C is sufficient to control intracranial hypertension, and that hypothermia below 35 degrees C may predispose patients to persistent cumulative oxygen debt. We attempted to clarify whether 35 degrees C hypothermia has the same effect as 33 degrees C hypothermia in reducing intracranial hypertension and whether it is associated with fewer complications and improved outcomes.
We compared intracranial pressure (ICP) and biochemical parameters in the 30 patients treated with 35 degrees C hypothermia (January 2000 to June 2005) with those in the 31 patients treated with 33 degrees C hypothermia (July 1994 to December 1999).
Patient characteristics were similar in the two groups. The mean temperature during hypothermia was 35.1 +/- 0.7 degrees C in the 35 degrees C hypothermia group and 33.4 +/- 0.8 degrees C in the 33 degrees C hypothermia group. Mean ICP was controlled under 20 mm Hg during hypothermia in both the 35 degrees C hypothermia and 33 degrees C hypothermia groups. The incidence of intracranial hypertension and low cerebral perfusion pressure did not differ between the two groups. The 35 degrees C hypothermic patients exhibited a significant improvement in the decline of serum potassium concentrations during hypothermia and in the increment of C-reactive protein after rewarming. The mortality rate and the incidence of systemic complications tended to be lower in the 35 degrees C group.
Cooling patients to 35 degrees C is safe and the ICP reduction effects of 35 degrees C hypothermia are similar to those of 33 degrees C hypothermia.
The Journal of trauma 02/2009; 66(1):166-73. · 2.48 Impact Factor
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ABSTRACT: Age is an important factor influencing outcome after severe traumatic brain injury (TBI). In general, the older the victim, the higher the probability of a poor outcome. To investigate the mechanism underlying the link between age and outcome, the data for 797 patients enrolled in the Japan Neurotrauma Data Bank (JNTDB), aged 6 years or older, with Glasgow Coma Scale (GCS) scores of 8 or less on admission or deterioration to that level within 48 h of impact were analyzed. Thirty-eight percent of the patients were between the ages of 40 and 69 years, and 24% of the patients were older than 69 years. Older patients had higher rates of mortality and lower rates of favorable outcome. The frequency of mass lesions which were associated with poorer outcomes significantly increased with age, but regardless of the intracranial lesion type, older patients had poorer outcomes. The GCS score and the occurrence of systemic complications did not differ significantly according to age. Multiple systemic injury was less frequent in older patients. The varied occurrence of intracranial lesion types according to age is likely caused by the disparity between the young and aged brain in the progression of secondary brain injury. Alteration in the pathophysiological response, which is related to the development of secondary brain injury in the aging brain, probably contributes to more severe and irreversible brain damage in older patients, and is thus associated with poor outcomes.
Journal of Neurotrauma 01/2009; 25(12):1407-14. · 3.65 Impact Factor
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ABSTRACT: According to current World Health Organization (WHO) criteria, counting mitotic figures (MF), which is equal to the mitotic index (MI), on paraffin sections stained with hematoxylin and eosin (HE) is one of the recognized classification methods for meningiomas. However, it is not always easy to find the area of highest mitotic activity, and there are different perspectives among pathologists with regard to differentiating MF from non-MF, i.e., which are apoptotic figures and which are crushed or distorted cells. Moreover, there is an issue of overgrading in meningiomas with preoperative feeder embolization. Recently, anti-phosphohistone-H3 (PHH3) antibody has been reported as a mitosis-specific marker for meningioma grading. In this study, we attempted PHH3 immunostaining for our meningioma cases and verified not only the sensitivity of PHH3 immunostaining but also that of its usefulness in grading meningiomas. Forty-five initial histologically confirmed meningiomas (37 benign, 7 atypical, and 1 anaplastic) were reviewed according to current WHO criteria based on counting MF on HE-stained slides. PHH3-immunostained MF were counted in the same way, and the MIB-1 labeling index (LI) was calculated for each sample. PHH3-labeled MF were easily identified and permitted rapid recognition of the areas of highest mitotic activity. As a result, significant increase of PHH3 mitotic index (PHH3-MI) in comparison with HE mitotic index (HE-MI) and strong correlations with HE-MI to PHH3-MI as well as PHH3-MI to MIB-1 LI were demonstrated. Furthermore, no significant differences of PHH3-MI between cases with and without feeder embolization were demonstrated. As such, PHH3 may be a sensitive and useful marker for meningioma grading as based on the MF.
Brain Tumor Pathology 01/2009; 26(2):51-7. · 1.19 Impact Factor
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ABSTRACT: The present experiment examined the effect of mild hypothermia (35 degrees C) on the post-traumatic hyperactivity of rat hippocampal CA1 neurons in horizontal brain slices. One week after fluid percussion injury (FPI), the optical response evoked by stimulation of the Schaffer collaterals increased in amplitude and propagation area in hippocampal CA1 slices. FPI did not alter the fast optical response that reflected the action potential of the Schaffer collaterals but enhanced the slow component that reflected the excitatory postsynaptic response. FPI increased the slope of the input-output relation (I/O function), suggesting that FPI increases the efficacy of excitatory synaptic transmission in the hippocampal CA1 pyramidal neurons. To examine the effect of low temperature on post-traumatic hyperactivity of hippocampal CA1 neurons, mild hypothermia (35 degrees C) was administered to rats 15 min after FPI and maintained for 1-3 h. One week after FPI, the activity of hippocampal CA1 neurons in rats with mild hypothermia appeared to be reduced as compared with those receiving FPI alone. The post-traumatic enhancement of the I/O function of the slow optical response was prevented by mild hypothermia. These results suggest that mild hypothermia applied 15 min after FPI attenuates the post-traumatic hyperactivity of excitatory synapses in rat hippocampal CA1 neurons.
The Kurume Medical Journal 01/2009; 56(3-4):49-59.
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ABSTRACT: The KIAA 0864 (KA) protein is a putative protein of a cDNA from 100 cDNA clones that was newly determined from a set of size-fractionated human brain cDNA libraries and their coding potentials of large proteins (180-200 kD) by using in vitro transcription assays. To elucidate the correlation between the KA protein and neuroepithelial tumors (NETs), the present study assessed the KA expression by the NETs using immunohistochemical and Western blot analyses with HFB-16 monoclonal antibody. Among the 55 NETs, a moderate-to-intense KA protein immunoreactivity was observed in 8 of 8 medulloblastomas, 1 of 1 central nervous system supratentorial primitive neuroectodermal tumor (CNS supratentorial PNET), 4 of 4 retinoblastomas, 1 of 1 neuroblastoma, 8 of 8 central neurocytomas, 4 of 4 oligodendrogliomas, 4 of 4 oligoastrocytomas, 1 of 1 extraventricular neurocytoma, and 1 of 1 gangliocytoma. No or a weak KA protein immunoreactivity was observed in 11 of 11 glioblastomas (GBs), 4 of 4 anaplastic astrocytomas, 4 of 4 astrocytomas, and 4 of 4 pilocytic astrocytomas. These results indicate that the antibody HFB-16 could be a useful marker for neuronal tumors and primitive neuroectodermal tumors that may originate from immature neural progenitor cells. In addition, it could be a useful tool for performing the differential diagnosis between GBs and CNS supratentorial PNET.
Journal of Neuro-Oncology 06/2008; 89(2):151-8. · 3.21 Impact Factor
