• 대한간호학회지
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• 제40권4호
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• pp.580-588
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• 2010

Purpose: The purpose of this study was to examine effects of decreased locomotor activity on mass, Type I and II fiber cross-sectional areas of ipsilateral and contralateral hindlimb muscles 21 days after establishing the Parkinson's disease rat model. Methods: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 50 ${mu}g$) into the left substantia nigra after stereotaxic surgery. Adult male Sprague-Dawley rats were assigned to one of two groups; the Parkinson's disease group (PD; n=17) and a sham group (S; n=8). Locomotor activity was assessed before and 21 days after the experiment. At 22 days after establishing the rat model, all rats were anesthetized and soleus and plantaris muscles were dissected from both ipsilateral and contralateral sides. The brain was dissected to identify dopaminergic neuronal death of substantia nigra in the PD group. Results: The PD group at 21 days after establishing the Parkinson's disease rat model showed significant decrease in locomotor activity compared with the S group. Weights and Type I and II fiber cross-sectional areas of the contralateral soleus muscle of the PD group were significantly lower than those of the S group. Conclusion: Contralateral soleus muscle atrophy occurs 21 days after establishing the Parkinson's disease rat model.

• 한국환경과학회지
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• 제32권10호
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• pp.723-729
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• 2023

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neuronal loss in the substantia nigra, resulting in reduced dopamine levels and consequent motor dysfunction. Genetic and environmental factors contribute to oxidative stress in PD. Cicadidae Periostracum (CP), a traditional Korean medicine, has shown neuroprotective effects against MPTP-induced neurotoxicity in PD. However, its effects on the 6-hydroxydopamine (6-OHDA) model have not been established. This study examined CP's effects on a 6-OHDA-induced PD model. CP protected against 6-OHDA damage in both in vitro and in vivo studies. Furthermore, CP reduced the production of reactive oxygen species, inhibited apoptosis, preserved dopamine levels, protected tyrosine hydroxylase in the substantia nigra, and improved motor function. These findings suggest that CP may delay PD progression by maintaining the redox balance.

• Journal of Korean Neurosurgical Society
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• 제30권6호
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• pp.688-698
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• 2001

Objectives : Parkinson's disease is a well-known neurodegenerative disease characterized by dopaminergic cell death in the substantia nigra. The reactive gliosis by activated astrocytes and microglias is no more regarded as a simple sequel of neuronal cell death. Microglial activation takes place in a stereotypic pattern with graded morphologic and functional(resting, activated and phagocytic) changes. In Parkinson's disease animal model, the degree of microglial activation along the nigro-striatal dopaminergic tract has not been studied intensively. The purpose of this study was to elucidate the characteristics of microglial reaction and to grade its degree of activation at substantia nigra and corpus striatum using 6-hydroxydopamine induced rat model of Parkinson's disease. Methods : Using Sprague-Dawley rat, parkinsonian model was made by 6-hydroxydopamine(OHDA) induced destruction of medial and lateral substantia nigra(SN). The rat was sacrificed 3-, 5-, 7-, 14- and 21-day-after operation. For control group, we injected saline with same manner and sacrificed 3-day after operation. With immunohistochemistry, we examined dopaminergic neuronal cells and microglial expression using tyrosine hydroxylase (TH) and OX-42 antibodies, respectively. Also we performed in situ hybridization for osteopontin, a possible marker of subset in activated microglia. Results : 1) In lesioned side of substantia nigra and corpus striatum, the TH immunoreactivity was markedly decreased in whole experimental groups. 2) Using optical densitometry, microglia induced immunoreactivity of OX-42 was counted at SN and corpus striatum. At SN, it was increased significantly on the lesioned side in control and all time-dependent experimental groups. At striatum, it was increased significantly in post lesion 3-day group only(p <0.05). Compared to control group, immunoreactivity of OX-42 on lesioned side was increased in groups, except post lesion 21-day group, at SN. Only post lesion 3-day group showed significance at striatum(p <0.05). Compared to SN region, immunoreactivity of OX-42 was much weaker in striatum. 3) Microscopically, the microglias showed typically different activation pattern. At SN, numerous phagocytic microglias were found at pars compacta and reticularis of lesion side. At striatum, no phagocytic form was found and the intensity of staining was much weaker. 4) At SN, the immunoreactivity of osteopontin showed definite laterality and it was markedly increased at pars compacta of lesion side with relatively short duration time. At striatum, however, it was not detected by in situ hybridization technique. Conclusion : The nigral 6-OHDA induced rat model of Parkinson's disease revealed several characteristic patterns of microglial reaction. At SN, microglias was activated shortly after direct neuronal damage and maintained for about three weeks. In contrast, despite of sufficient dopaminergic insufficiency at striatum, activation of microglias was trivial, and distinguished 3 day later. Antegrade slow neuronal degeneration is major pathophysiology in striatal dopaminergic deficiency. So, the acuteness of neuronal damage and consequential degree of neuronal degeneration may be important factor for microglial activation in neurodegenerative diseases such as Parkinson's disease. Additionally, osteopontin may be a possible marker for several subsets of activated microglia, possibly the phagocytic form.

• 대한약리학회지
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• 제30권1호
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• pp.39-48
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• 1994

포만중추 (satiety center)를 자극하여 음식섭취를 억제한다고 알려진 CCK-8을 흰쥐 복강에 투여하여, 흰쥐 뇌의 도파민 변화에 대한 CCK-8의 효과를 관찰하였다. 흰쥐 뇌의 부위별 도파민 함량은 HPLC-ECD방법으로 측정하였으며, 시상하부와 흑질에서의 TH-immunoreactive neuron은 면역조직화학법과 영상분석법을 시행하였다. 굶긴 쥐에서는 정상 쥐에 비하여, 도파민 함량이 전두 피질, 해마, 시상하부 및 편도체에서 각각 감소하였다. CCK-8을 투여한 쥐는 정상 쥐와 굶긴 쥐에 비하여, 도파민 함량이 시상하부에서 의미있게 감소하였다. 또한 굶긴 쥐는 정상 쥐와 비교하여, TH-positive neuron의 분포와 수가 뇌실옆핵, 깔때기핵, 정중융기 및 혹질에서 현저히 감소하였다. CCK-8투여시, 시상하부와 흑질에서의 TH-immunoreactive neuron의 수는 굶긴 쥐에 비하여 증가하였다. 이상의 실험 결과로 보아 음식물 섭취를 억제하는 작용이 있는 CCK-8은 시상하부의 도파민 신경계와 일부분 관련되어 있으며, 또한 시상하부와 흑질에 존재하는 TH-positive neuron은 음식물 섭취 행위에 중요한 역할이 있음을 시사하고 있다.

• 한국자기공명학회논문지
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• 제5권2호
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• pp.99-109
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• 2001

Authors investigated neuronal changes of local cellular metabolism in the cerebral lesions of Parkinsonian symptomatic side between before and after stereotactic neurosurgery by follow-up 1H magnetic resonance spectroscopy (MRS). Patients with Parkinson's disease (PD) (n = 15) and age-matched normal controls (n = 15) underwen MRS examinations using a stimulated echo acquisition mode (STEAM) pulse sequence that provided 2${\times}$2${\times}$2 ㎤ (8ml) volume of interest in the regions of substantia nigra, thalamus, and lentiform nucleus. Spectral parameters were 20 ms TE, 2000 ms TR, 128 averages,2500 Hz spectral width, and 2048 data points. Raw data were processed by the SAGE data analysis package (GE Medical Systems). Peak areas of N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), inositols (Ins), and the sum (Glx) of glutamate and GABA were calculated by means of fitting the spectrum to a summation of Lorentzian curves using Marquardt algorithm. After blindly processed, we evaluated neuronal alterations of observable metabolite ratios between before and after stereotactic neurosurgery using Pearson product-moment analysis (SPSS, Ver. 6.0). A significant reduction of NAA/Cho ratio was observed in the cerebral lesion in substantia nigra of PD patient related to the symptomatic side after neurosurgery (P : 0.03). In thalamus, NAA/Cho ratio was also significantly decreased in the cerebral lesion including the electrode-surgical region (P : 0.03). A significant reduction of NAA/Cho ratio in lentiform nucleus was not oberved, but tended toward significant reduction after neurosurgery (P = 0.08). In particular, remarkable lactate signal was noted from the surgical thalamic lesions of 6 among 8 patients and internal segments of globus pallidus of 6 among 7 patients, respectively. Significant metabolic alterations of NAA/Cho ratio might reflect functional changes of neuropathological processes in the lesion of substantia nigra, thalamus, and lentiform nucleus, and could be a valuable finding fur evaluation of Parkinson's disease after neurosurgery. Increase of lactate signals, being remarkable in surgical lesions, could be consistent with a common consequence of neurosurgical necrosis. Thus, IH MRS could be a useful modality to evaluate the diagnostic and prognostic implications fur Parkinsons disease after functional neurosurgery.

• Korean Journal of Radiology
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• 제25권3호
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• pp.267-276
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• 2024

Objective: To evaluate the diagnostic performance of susceptibility map-weighted imaging (SMwI) taken in different acquisition planes for discriminating patients with neurodegenerative parkinsonism from those without. Materials and Methods: This retrospective, observational, single-institution study enrolled consecutive patients who visited movement disorder clinics and underwent brain MRI and ¹⁸F-FP-CIT PET between September 2021 and December 2021. SMwI images were acquired in both the oblique (perpendicular to the midbrain) and the anterior commissure-posterior commissure (AC-PC) planes. Hyperintensity in the substantia nigra was determined by two neuroradiologists. ¹⁸F-FP-CIT PET was used as the reference standard. Inter-rater agreement was assessed using Cohen;s kappa coefficient. The diagnostic performance of SMwI in the two planes was analyzed separately for the right and left substantia nigra. Multivariable logistic regression analysis with generalized estimating equations was applied to compare the diagnostic performance of the two planes. Results: In total, 194 patients were included, of whom 105 and 103 had positive results on ¹⁸F-FP-CIT PET in the left and right substantia nigra, respectively. Good inter-rater agreement in the oblique (κ = 0.772/0.658 for left/right) and AC-PC planes (0.730/0.741 for left/right) was confirmed. The pooled sensitivities for two readers were 86.4% (178/206, left) and 83.3% (175/210, right) in the oblique plane and 87.4% (180/206, left) and 87.6% (184/210, right) in the AC-PC plane. The pooled specificities for two readers were 83.5% (152/182, left) and 82.0% (146/178, right) in the oblique plane, and 83.5% (152/182, left) and 86.0% (153/178, right) in the AC-PC plane. There were no significant differences in the diagnostic performance between the two planes (P > 0.05). Conclusion: There are no significant difference in the diagnostic performance of SMwI performed in the oblique and AC-PC plane in discriminating patients with parkinsonism from those without. This finding affirms that each institution may choose the imaging plane for SMwI according to their clinical settings.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.113-113
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• 2001

Dopamine, a principal neurotransmitter in the central nervous system, accounts for 90% of total catecholamines. It serves as a precursor of certain hormones, melanins, noradrenalin and adrenalin. Parkinsonian disease (PD) is characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta and a significant dimunution in the neostriatal content of dopamine and its metabolites.(omitted)

• Animal cells and systems
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• 제1권3호
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• pp.497-505
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• 1997

Dopamine plays diverse roles in the fetal brain development and differentiation. However, the development of the dopaminergic neurons and its receptors has not been fully understood. In our studies, in situ hybridization and immunohistochemical methods were used to investigate the ontogeny of dopaminergic neurons and its receptor subtypes during the fetal development of the rat. In situ hybridization data showed that dopamine $D_1$ and $D_2$ receptor mRNAs were expressed in the ventricular and subventricular zones of ganglionic eminence, thalamus, hypothalamus, and cortical neuroepithelium on gestational day 13. Expression of dopamine $D_1$ and $D_2$ receptors during gestational days 17 and 19 reached the same or similar level of that in the adult brain. Expression of $D_1$ receptor mRNA preceded that of $D_2$ receptor mRNA in the early developmental stage, although this pattern was reversed with the sharp increase of $D_2$ receptor mRNA soon after. $D_2$ receptor mRNA was expressed in substantia nigra of mesencephalon of the fetal rat brain. However, $D_1$ receptor mRNA was not detected in substantia nigra. Our results indicate that dopamine might function in the fetal brain during the early gestational period.

• Animal cells and systems
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• 제15권4호
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• pp.279-286
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• 2011

Hypoxic ischemia injury is a common cause of functional brain damage, resulting from a decrease in cerebral blood flow and oxygen supply to the brain. The main problems associated with hypoxic ischemia to the brain are memory impairment and dopamine dysfunction. Hypothermia has been suggested to ameliorate the neurological impairment induced by various brain insults. In this study, we investigated the effects of hypothermia on memory function and dopamine synthesis following hypoxic ischemia to the brain in rats. For this purpose, a step-down avoidance task, a radial eight-arm maze task, and immunohistochemistry for tyrosine hydroxylase (TH) and 5-bromo-2'-deoxyuridine (BrdU) were performed. The present results indicated that the hypoxic ischemia-induced disturbance of the animal's performances and spatial working memory was associated with a decrement in TH expression in the substantia nigra and striatum, and an increase in cell proliferation in the hippocampal dentate gyrus. Hypothermia treatment improved the animals' performance and spatial working memory by suppressing the decrement in TH expression in the substantia nigra and striatum and the increase in cell proliferation in the dentate gyrus. We suggest that hypothermia can be an efficient therapeutic modality to facilitate recovery following hypoxic ischemia injury to the brain, presumably by modulating the dopaminergic cell loss.

• 생물정신의학
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• 제3권2호
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• pp.191-202
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• 1996

This study was aimed to charily the change of NADPH-diaphorase(NADPH-d) and neuropeptide Y(NPY) associated with aging of the rots. To verily the effect of aging of NPY and NADPH-d-positive neurons in the brain stem, the neurons were stained by the immunohistochemical and histochemical method. In the aged group, the number of NADPH-d-positive neurons was significantly decreased in substantia nigra lateralis, supragenual nucleus, raphe magnus nucleus and raphe obscurus nucleus as compared with control group. The number of NADPH-d-positive neurons was not significantly decreased in superior colliculus, interpeduncular nucleus, central gray. dorsal raphe nucleus, retrorubral nucleus, pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus, pontine reticular nucleus, prepositus hypoglossal nucleus and nucleus solitarius of the aged rats. The NADPH-d and NPY-positive neurons were found in the interpeduncular nucleus, central gray, substantia nigra lateralis, laterodorsal tegmental nucleus, nucleus solitarius, raphe magnus nucleus, raphe obscurus nucleus of the control and aged groups. The coexistence of NADPH-d and NPY in the some cell was not found in the brain stem of both groups.