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Biomedical subjects

Minoru Fujiki

Publications and source records attributed to Minoru Fujiki.

At least 19 recordsLinked to original sources
PubMed2006

Induced angiogenesis under cerebral ischemia by cyclooxygenase 2 and hypoxia-inducible factor naked DNA in a rat indirect-bypass model.

We recently reported that hypoxic stress induces the expression of HIF-1alpha, HIF-2alpha, cyclooxygenases-2 (COX-2) and VEGF in vivo. In this study, we investigated whether HIF-1alpha, HIF-2alpha, or COX-2 naked DNA induced angiogenesis in a cerebral ischemic model in vivo. We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated naked DNA into the brain surface. We analyzed whether DNA induced angiogenic factors and neovascularization. New blood vessel formation was detected by anti-Factor VIII staining. A histological section treated with HIF-2alpha or COX-2 DNA showed an increased expression of VEGF with angiogenesis, in comparison to the control DNA. The HIF-1alpha, HIF-2alpha, and COX-2 are able to promote significant angiogenesis development. These results suggest the feasibility of a novel approach for therapeutic angiogenesis of cerebral ischemia in which neovascularization may be indirectly achieved using a transcriptional and cytokine's regulatory strategy.

Animals↗
PubMed2006

Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment.

The present study used short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI) to evaluate motor cortex excitability in 16 diffuse axonal injury (DAI) patients with memory impairment and compared the data with those of 16 healthy controls. SAI was reduced in patients compared with controls (92+/-12 versus 39+/-11% of the test size; p<0.0001, unpaired t-test). DAI patients tended to have a high resting motor threshold (RMT) and less pronounced SICI and ICF than controls, but these differences were not significant. A single oral dose (3mg) of donepezil, an acetylcholinesterase inhibitor that is commonly used to treat Alzheimer's disease (AD), improved SAI in DAI patients with wide individual variations that ranged from an increase of 77-18% of test size. These findings suggest that measuring SAI may provide a means of probing the integrity of cholinergic networks in an injured human brain.

Adult↗
PubMed2006

Geranylgeranylacetone, a noninvasive heat shock protein inducer, induces protein kinase C and leads to neuroprotection against cerebral infarction in rats.

Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein (HSP) inducer, against ischemic insult. Protein kinase C (PKC) is thought to be an important factor that mediates the expression of heat shock protein 70 (HSP70) in vitro. However, the signaling pathways in the brain in vivo after oral GGA administration remain unclear. We measured and compared infarction volumes to investigate the effect of GGA on cerebral infarction induced by permanent middle cerebral artery (MCA) occlusion in rats. To clarify the relationship between PKC induction and HSP70 expression, we determined the amounts of HSP70 and PKC proteins after GGA administration by immunoblotting. We evaluated the effects of pretreatment with chelerythrine (CHE), a specific PKC inhibitor, on expressions of PKC and HSP70 proteins with immunoblotting. Neuroprotective effects of GGA (pretreatment with a single oral GGA dose (800 mg/kg) 48 h before ischemia) were prevented by CHE pretreatment, which indicates that PKC may mediate the GGA-dependent protection. Oral GGA-induced HSP70 expression induced PKC delta, and GGA pretreatment enhanced ischemia-induced HSP70, both of which were prevented by CHE pretreatment. These results suggest that a single oral dose of GGA induces PKC delta and promotes HSP70 expression in the brain and that GGA plays an important role in neuroprotection against cerebral ischemia.

Alkaloids↗
PubMed2006

Role of protein kinase C in neuroprotective effect of geranylgeranylacetone, a noninvasive inducing agent of heat shock protein, on delayed neuronal death caused by transient ischemia in rats.

We evaluated the neuroprotective effect of geranylgeranylacetone (GGA), an antiulcer agent and inducing agent of heat-shock protein (HSP), against the delayed death of hippocampal neurons induced by transient bilateral occlusion of the common carotid artery (CCA) and hypotension (40 mm Hg) lasting for 10 min. To test the hypothesis that orally administered GGA would induce protein kinase C (PKC), leading to the expression of HSP70 and protection against delayed neuronal death (DND), we gave GGA orally to rats in various regimens prior to bilateral occlusion of the CCA, and quantitatively assessed the extent of DND in region CA1 of the hippocampus at 7 days after transient ischemia. Pretreatment with a single oral dose of GGA of 800 mg/kg at 48 h before ischemia significantly attenuated DND (20.0 +/- 3.81 vs. 321.0 +/- 11.01 mm(3); p < 0.05). A similar degree of neuron sparing occurred when GGA was given 2, 4, or 8 days before ischemia. These neuroprotective effects of GGA were prevented by pretreatment with chelerythrine (CHE), a specific inhibitor of PKC, indicating that PKC may mediate GGA-dependent protection against ischemic DND. Oral GGA-induced expression of HSP70 elicited the expression of PKCdelta, and pretreatment with GGA enhanced the ischemia-induced expression of HSP70, both of which effects were prevented by pretreatment with CHE. These results suggest that a single oral dose of GGA induces the expression of PKCdelta and promotes the expression of HSP70 in the brain, and that GGA plays an important role in neuroprotection against DND. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against DND of hippocampal neurons after transient ischemia.

Animals↗
PubMed2006

Benign pleomorphic astrocytoma in the hypothalamus--case report.

A 41-year-old woman presented with an unusual case of benign astrocytoma with marked pleomorphism manifesting as consciousness disturbance due to intraventricular hemorrhage. Magnetic resonance imaging revealed a well-enhanced hypothalamic mass protruding into the third ventricle. Despite partial resection of the tumor without additional therapy, there have been no signs of tumor regrowth for 6 years. The histological findings revealed solid proliferation of tumor cells with marked pleomorphism, contrary to the benign clinical course. However, no mitosis, necrosis, or endothelial proliferation were found and the MIB-1 index was less than 0.5%. Immunohistochemical staining indicated the glial origin of the tumor. The tumor was similar to pleomorphic xanthoastrocytoma, but the histological findings were not exactly identical, indicating a new histological entity.

Adult↗
PubMed2006

Intraoperative corticomuscular motor evoked potentials for evaluation of motor function: a comparison with corticospinal D and I waves.

OBJECT: The goal of this study was to compare motor evoked potentials recorded from muscles (muscle MEPs or corticomuscular MEPs) with corticospinal MEPs recorded from the cervical epidural space (spinal MEPs or corticospinal MEPs) to assess their efficacy in the intraoperative monitoring of motor function. METHODS: Muscle and spinal MEPs were simultaneously recorded during surgery in 80 patients harboring brain tumors. Each case was assigned to one of four groups according to final changes in the MEPs: (1) Group A, in which there was an increased amplitude in the muscle MEP with an increased 13 wave amplitude (12 cases); (2) Group B, in which there was no significant change in the MEP (43 cases); (3) Group C, in which there was a decreased muscle MEP amplitude (< 35% of the control) with a decreased I wave amplitude but an unchanged D wave (15 cases); or (4) Group D, in which there was an absent muscle MEP with a decreased D wave amplitude (10 cases). In patients in Group A, the increase in the amplitude of the muscle MEP (range of increase 128-280%, mean increase 188.75 +/- 48.79%) was well correlated with the increase in the 13 wave in corticospinal MEPs. Most of these patterns were observed in patients harboring meningiomas (10 [83.3%] of 12 cases). Patients in Group B displayed no changes in muscle and corticospinal MEPs and no signs of postoperative neurological deterioration. Patients in Group C showed a substantial decrease in the amplitude of the muscle MEP (range of decrease 5.3-34.8% based on the control waveform, mean change 21.81 +/- 10.93%) without deterioration in the corticospinal D wave, and exhibited severe immediate postoperative motor dysfunction. This indicates dysfunction of the cortical gray matter, including the motor cortices, which are supposed to generate I waves. Patients in Group D exhibited decreases in the corticospinal D wave (range of decrease 21.5-55%, mean decrease 39.75 +/- 11.45%) and an immediate cessation of the muscle MEP as well as severe permanent motor paresis. CONCLUSIONS: These results indicate that, during surgery, monitoring of corticomuscular MEPs (which are related to I waves) is a much more sensitive method for the detection of immediate motor cortical damage than monitoring of corticospinal MEPs (D wave).

Adolescent↗
PubMed2005

Geranylgeranylacetone limits secondary injury, neuronal death, and progressive necrosis and cavitation after spinal cord injury.

This study evaluates the neuroprotective effects of geranylgeranylacetone (GGA), which is known as an antiulcer agent and more recently as a heat-shock and other neuroprotective protein inducer, on secondary degeneration after spinal cord injury in rats. Crush injuries were produced at the T8 level using an extradural approach. Optimal administration conditions of GGA were established in an initial experiment by evaluating the appearance of lesions 24 h after injury in sections stained with H-E. Then, in a second experiment, animals treated with the optimal condition (600 mg/kg, 24 h before injury and thereafter every 24 h) were allowed to survive for 6 and 24 h and 1, 3, and 8 weeks after injury, and spinal cords were prepared for histological evaluation by staining for H-E for general histopathology and by silver staining for axons. There was a significant reduction (46%) in lesion volume 24 h after injury in animals treated with optimal administration conditions. The increase in tumor necrosis factor-alpha (TNF-alpha) and the accumulation of neutrophils in the damaged segment of the spinal cord 4 h after injury were significantly inhibited in animals that received GGA. Lesion size and cavitation area remained smaller in treated animals throughout the post-injury survival interval. These results suggest that GGA administration significantly reduces the secondary degeneration that would otherwise occur. The mechanism by which GGA exerts its beneficial effect is unknown but may involve reduction of TNF-alpha activation at the injured cord and/or inhibition of inflammation.

Animals↗
PubMed2005

Neuroprotective effect of donepezil, a nicotinic acetylcholine-receptor activator, on cerebral infarction in rats.

This study evaluated the potential effect of donepezil, which is known as an acetylcholinesterase inhibitor used for treatment of Alzheimer's disease, against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion. Donepezil was given orally in various regimens, prior to MCA occlusion in rats. Pretreatment with a single oral dose of donepezil (12 mg/kg), 2 h before ischemia, significantly attenuated cerebral infarction volume (165.5 +/- 105.3 vs. 377.1 +/- 48.5 mm(3); P < 0.05). These neuroprotective effects were prevented by coinjection with mecamylamine, a nicotinic acetylcholine-receptor (nAChR) antagonist, indicating that protection was mediated by nAChR activation.

Animals↗
PubMed2005

Anxiolytic suppression of repetitive transcranial magnetic stimulation-induced anxiety in the rats.

Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment of several psychiatric disorders such as depression and anxiety disorder. However, some reports suggest that rTMS induced anxiety in normal volunteers. Consistent with this observation, we have reported that chronic rTMS induces anxiety in normal rats which was suppressed by chronic treatment, but not acute paroxetine treatment. The current study evaluates rTMS as animal model of anxiety by investigating the effect of rTMS on anxiety behaviors and the ability of standard anxiolytics to block expression of these behaviors. We found that 10-day rTMS induced anxiety in normal rats, as evidenced by expression of anxiety behaviors in the elevated plus-maze. This anxiety was suppressed by acute treatment with diazepam, alprazolam, or buspirone suggesting that chronic rTMS treatment provides a good animal model for anxiety.

Acoustic Stimulation↗
PubMed2005

Hypoxia-inducible factor-1alpha DNA induced angiogenesis in a rat cerebral ischemia model.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a constitutively expressed subunit, HIF-1beta. In this study, we investigated HIF-1alpha naked DNA-induced angiogenesis in a cerebral ischemic model in vivo. METHODS: We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated HIF-1alpha DNA into the brain surface or the temporal muscle. We analysed whether HIF-1alpha induced angiogenic factors and collateral circulation. RESULTS: A histological section treated with HIF-1alpha DNA showed an increased expression of HIF1 a and VEGF with collateral circulation, in comparison with control DNA (p < 0.01). The HIF-1alpha transcription factor is able to promote significant angiogenesis development. CONCLUSION: These results suggest the feasibility of a novel approach for therapeutic collateral circulation of cerebral ischemia in which neovascularization may be achieved indirectly using a transcriptional regulatory strategy.

Animals↗
PubMed2004

Neuroprotective effect of geranylgeranylacetone, a noninvasive heat shock protein inducer, on cerebral infarction in rats.

The present study evaluated the neuroprotective effect of geranylgeranylacetone (GGA), which is known as an antiulcer agent and more recently as a heat shock protein (HSP) inducer, against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion. GGA was given orally in various regimens prior to MCA occlusion in rats. Pretreatment with a single oral GGA dose (800 mg/kg) 48 h before ischemia significantly attenuated cerebral infarction volume (81.7+/-18.4 mm3 versus 369.1+/-70.2 mm3; P<.01). A significant increase in HSP70 immunoreactivity was found in the neocortex in GGA-treated animals with or without ischemia. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against cerebral ischemic neuronal damage.

Animals↗
PubMed2004

A single oral dose of geranylgeranylacetone attenuates kainic acid-induced seizures and neuronal cell death in rat hippocampus.

The present study evaluated the potential effect of geranylgeranylacetone (GGA), which is known as an antiulcer agent, against kainic acid (KA)-induced neurotoxicity. Pretreatment with a single oral GGA dose (800 mg/kg, 2 days before KA) significantly attenuated KA-induced seizures and cell death in rat hippocampus. These effects of GGA were prevented by the coinjection of MK801, a noncompetitive N-methyl-D-aspartate glutamate receptor antagonist, which indicates that the protection was indeed mediated by glutamate receptor activation.

Administration, Oral↗
PubMed2004

Single oral dose of geranylgeranylacetone for protection against delayed neuronal death induced by transient ischemia.

The present study evaluated the potential effect of geranylgeranylacetone (GGA), which is known as an antiulcer agent, against the delayed neuronal death (DND) of hippocampal neurons an otherwise lethal ischemic insult. Pretreatment with single oral GGA (800 mg/kg, 2 days before ischemia) significantly attenuated DND in gerbil hippocampus. These effects of GGA were prevented by the coinjection of MK801, a noncompetitive N-methyl-d-aspartate glutamate receptor antagonist, which indicates that the protection was indeed glutamate receptor activation mediated.

Administration, Oral↗
PubMed2004

Immediate plasticity in the motor pathways after spinal cord hemisection: implications for transcranial magnetic motor-evoked potentials.

The present study evaluates motor functional recovery after C2 spinal cord hemisection with or without contralateral brachial root transection, which causes a condition that is similar to the crossed phrenic phenomenon on rats. Descending motor pathways, including the reticulospinal extrapyramidal tract and corticospinal pyramidal tracts, were evaluated by transcranial magnetic motor-evoked potentials (mMEPs) and direct cortical electrical motor-evoked potentials (eMEP), respectively. All MEPs recorded from the left forelimb were abolished immediately after the left C2 hemisection. Left mMEPs recovered dramatically immediately after contralateral right brachial root transection. Corticospinal eMEPs never recovered, regardless of transection. The facilitation of mMEPs in animals that had undergone combined contralateral root transection was well correlated with open-field behavioral motor performance. Both electrophysiological and neurological facilitations were significantly attenuated by the selective serotonin synthesis inhibitor para-chlorophenylalanine (p-CPA). These results suggest that serotonergic reticulospinal fibers located contralateral to hemisection contribute to the behavioral and electrophysiological improvement that immediately follows spinal cord injury (SCI).

Animals↗
PubMed2004

Electrical preconditioning attenuates progressive necrosis and cavitation following spinal cord injury.

This study evaluates the influence of preconditioning and subsequent electrical stimulation on the formation of primary and secondary lesions following spinal cord injury in rats. The dorsal surface of the spinal cord at the T7 level was stimulated 24 h before right-side hemisection (500 Hz, 10 pulses/train, at an inter-train interval of 10 sec for 2 h). Stimulation was again administered immediately after injury and then every 24 h for 7 days. Preconditioning electrical stimulation of the spinal cord activated reactive astrocytes, then significantly attenuated edema, progressive necrosis, and cavitation, especially in the secondary cavity lesions (24 h, 1 week, and 3 weeks post-injury). Upregulation of glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity, a measure of reactive astrocytic response, were increased at 1 week after injury in the rats treated with electrical stimulation. These results suggest that preconditioning with electrical stimulation prevents the formation of secondary lesions after spinal cord injury. This beneficial effect may be related to the ability of electrical stimulation to attenuate trauma-induced cellular cascades.

Animals↗
PubMed2004

IkappaBalphaM suppresses angiogenesis and tumorigenesis promoted by a constitutively active mutant EGFR in human glioma cells.

Human glioma cell lines (G36DeltaEGFR and IN500DeltaEGFR) have been shown to display an enhanced tumorigenic phenotype, when transfected with a constitutively active form of the epidermal growth factor receptor (DeltaEGFR). These cells were transfected with a mutant IkappaBalpha (IkappaBalphaM) that is resistant to phosphorylation and degradation, and hence blocks NF-kappaB activity. Recently, EGFR has been shown to increase the activity of NF-kappaB and to induce angiogenesis. In this report, we asked if IkappaBalphaM gene transfer into human glioma cell lines would inhibit tumorigenicity and angiogenesis in glioma. IkappaBalphaM inhibited in vitro and in vivo expression of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). Human glioma xenografts treated with IkappaBalphaM gene transfer exhibited significantly decreased angiogenesis both in an orthotopic and in an ectopic model. The decreased expression of VEGF and IL-8 directly correlated with decreased tumorigenicity, and tumor vascularization. Taken in combination, these results provide strong evidence of IkappaBalphaM's role in regulating glioma angiogenesis even in the presence of constitutive EGFR activation.

Animals↗
PubMed2004

Remote cerebellar hemorrhage following supratentorial craniotomy--case report.

A 63-year-old man presented with sudden severe headache. Computed tomography (CT) demonstrated subarachnoid hemorrhage. Cerebral angiography demonstrated an aneurysm of the anterior communicating artery. Left frontotemporal craniotomy and neck clipping of the aneurysm via the pterional approach were performed. CT obtained 18 hours after surgery revealed cerebellar hemorrhage, and magnetic resonance (MR) imaging 17 days postoperatively demonstrated that the hemorrhage was located within the folia. Neurological examination after surgery revealed slight dysarthria after drainage of cerebrospinal fluid (CSF) but no other neurological deficits. Follow-up CT and MR imaging showed characteristic findings of postoperative cerebellar hemorrhage clearly different from those of hypertension. The cerebellar hemorrhage was probably secondary to overdrainage of CSF. He was discharged without deficits.

Carotid Arteries↗