MDPIActa Medica Okayama2227-9059972021Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson's Disease Model Rats789ENIttetsuKinDepartment of Neurological Surgery, Okayama University Graduate School of MedicineTatsuyaSasakiDepartment of Neurological Surgery, Okayama University Graduate School of MedicineTakaoYasuharaDepartment of Neurological Surgery, Okayama University Graduate School of MedicineMasahiroKamedaDepartment of Neurological Surgery, Okayama University Graduate School of MedicineTakashiAgariDepartment of Neurosurgery, Tokyo Metropolitan Neurological HospitalMihokoOkazakiDepartment of Neurological Surgery, Okayama University Graduate School of MedicineKakeruHosomotoDepartment of Neurological Surgery, Okayama University Graduate School of MedicineYosukeOkazakiDepartment of Neurological Surgery, Okayama University Graduate School of MedicineSatoruYabunoDepartment of Neurological Surgery, Okayama University Graduate School of MedicineSatoshiKawauchiDepartment of Neurological Surgery, Okayama University Graduate School of MedicineKenKuwaharaDepartment of Neurological Surgery, Okayama University Graduate School of MedicineJunMorimotoDepartment of Neurological Surgery, Okayama University Graduate School of MedicineKyoheiKinDepartment of Neurological Surgery, Okayama University Graduate School of MedicineMichiariUmakoshiDepartment of Neurological Surgery, Okayama University Graduate School of MedicineYousukeTomitaDepartment of Neurological Surgery, Okayama University Graduate School of MedicineNaokiTajiriDepartment of Neurophysiology and Brain Science and Medical School, Graduate School of Medical Sciences and Medical School, Nagoya City UniversityCesario, VBorlonganDepartment of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd.IsaoDateDepartment of Neurological Surgery, Okayama University Graduate School of MedicineBackground: The major surgical treatment for Parkinson's disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats. Methods: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA). Results: VNS with 0.25-0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy. Conclusions: VNS with 0.25-0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1353-80202042014Cognitive functions in Parkinson's disease: Relation to disease severity and hallucination415420ENTakaakiWakamoriTakashiAgariTakaoYasuharaMasahiroKamedaAkihikoKondoAikoShinkoSusumuSasadaTatsuyaSasakiTomohisaFurutaIsaoDateObjective: We wished to relate severity of Parkinson's disease (PD) with cognitive function in relation to cerebral blood flow (CBF).
Methods: Eighty-one consecutive PD patients were enrolled in this study. We used Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Third edition (WAIS-III) to evaluate cognitive functions, and three-dimensional stereotactic ROI template (3DSRT) and Statistical Parametric Mapping (SPM) 8 to evaluate single photon emission CT (SPECT) recordings of regional CBF.
Results: The mean MMSE score of PD patients was 27.4 +/- 2.4. The scores of most patients were higher than 23/30. On the other hand, the mean Full-scale IQ of PD patients was 88.4 +/- 17.3 in WAIS-III, which was lower than that of normal controls. In particular, visuospatial function score of most patients was lower. There was significant correlation between cognitive scores and Hoehn & Yahr stage and hallucinatory episodes. PD Patients with stage III and IV showed significant deterioration in cognitive functions compared to stage II patients. Analysis of CBF revealed relative reductions in perfusion in the cerebral cortex relative to that in normal control. SPM 8 showed that cognitive functions in PD patients were positively correlated with rCBF in the thalamus and cingulate gyrus.
Conclusions: This is the study to demonstrate the cognitive impairments in PD patients using WAIS-III. Visuospatial dysfunction might be caused by decrease in rCBF in the parietal and occipital lobes and dorsolateral prefrontal cortex. The severity of cognitive impairments in PD patients was correlated with disease severity and hallucinatory episodes.No potential conflict of interest relevant to this article was reported.Elsevier Science BvActa Medica Okayama0006-899315022013The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease5570ENJudith ThomasTayraMasahiroKamedaTakaoYasuharaTakashiAgariTomohitoKadotaFeifeiWangYoichiroKikuchiHanbaiLiangAikoShinkoTakaakiWakamoriBrigittaVcelarRobertWeikIsaoDateParkinson's disease is characterized by progressive degeneration of dopaminergic neurons. Thus the development of therapeutic neuroprotection and neurorescue strategies to mitigate disease progression is important. In this study we evaluated the neuroprotective/rescue effects of erythropoietin Fc fusion protein (EPO-Fc) and carbamylated erythropoietin Fe fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. Adult female Sprague-Dawley rats received intraperitoneal injection of EPO-Fc, CEPO-Fc or PBS. Behavioral evaluations consisted of rota-rod, cylinder and amphetamine-induced rotation tests. In the neuroprotection experiment, the CEPO-Fc group demonstrated significant improvement compared with the EPO-Fc group on the amphetamine-induced rotation test throughout the four-week follow-up period. Histologically, significantly more tyrosine hydroxylase (TH)-positive neurons were recognized in the substantia nigra (SN) pars compacta in the CEPO-Fc group than in the PBS and EPO-Fc groups. In the neurorescue experiment, rats receiving CEPO-Fc showed significantly better behavioural scores than those receiving PBS. The histological data concerning striatum also showed that the CEPO-Fc group had significantly better preservation of TH-positive fibers compared to the PBS and EPO-Fc groups. Importantly, there were no increases in hematocrit or hemoglobin levels in the CEPO-Fc group in either the neuroprotection or the neurorescue experiments. In conclusion, the newly developed CEPO-Fc might confer neuroprotective and neurorescue benefits in a rat model of Parkinson's disease without the side effects associated with polycythemia. CEPO-Fc might be a therapeutic tool for patients with Parkinson's disease.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6662012Successful Treatment of Epilepsy by Resection of Periventricular Nodular Heterotopia487492ENTakashiAgariTadahiroMiharaKoichiBabaKatsuhiroKobayashiNaotakaUsuiKiyohitoTeradaFumihiroNakamuraKazumiMatsudaIsaoDateCase Report10.18926/AMO/49045We report on a case of successful surgical treatment of drug-resistant epilepsy associated with a solitary lesion of periventricular nodular heterotopia (PNH). In the reported patient, intracranial ictal electroencephalography disclosed that seizures did not originate from the heterotopic nodules. However, the seizures were completely suppressed by lesionectomy of PNH alone. Epileptogenesis associated with PNH likely involves a very complex network between PNH and the surrounding cortex, and the disruption of this network may be an effective means of curing intractable, PNH-associated epilepsy.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2008Intrapallidal metabotropic glutamate receptor activation in a rat model of Parkinsonfs disease: Behavioral and histological analysesENTakashiAgariNo potential conflict of interest relevant to this article was reported.ͺRγwοActa Medica Okayama0030-155811822006_oΎ³ΙΞ·ιJvZ»ΧEΪA99103ENNo potential conflict of interest relevant to this article was reported.