Evaluation of a multiple system atrophy model in rats using multitracer microPET

Yoon, Hyun Soo; Lee, Chong Sik; Hong, Seok Ho; Min, Joongkee; Kim, Yong Hwan; Hwang, Onyou; Jeon, Sang Ryong

doi:10.1007/s00701-011-1133-z

Cited by 4 publications

(6 citation statements)

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“…This imaging method can diagnose the state of PD more precisely than behavior tests. [ 18 F]-FP-CIT microPET images were useful and consistent indicators of movement disorders in a rat model in our previous reports 29 , 30) . In this study, there was a significant increase in [ 18 F]-FP-CIT uptake by 10 weeks posttransplantation compared to the pretransplantation state.…”

Section: Discussionsupporting

confidence: 72%

Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

Shin

Hwang

et al. 2014

J Korean Neurosurg Soc

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ObjectiveNeural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions.MethodsRats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[18F]-fluoro-D-glucose ([18F]-FDG) and [18F]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([18F]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results.ResultsThe stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [18F]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human β2 microglobulin (a human cell marker) positive cells were visualized at the transplant site.ConclusionThese results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.

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Section: Discussionsupporting

confidence: 72%

Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

Shin

Hwang

et al. 2014

J Korean Neurosurg Soc

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“…In previous studies, the apomorphine-induced rotation test revealed an increase in contralateral rotations after injection of 6-OHDA into the MFB, and a decrease in contralateral rotations after subsequent injection of QA into the ipsilateral striatum ( 12 , 24 ). However, the decrease in contralateral rotations after injection of QA into the striatum can spontaneously recover without any treatment ( 12 , 24 ). The mechanism underlying this spontaneous recovery after sequential double toxin-double lesion is not clear, but it is possible that the QA-induced lesion in the striatum was insufficient to generate persistent rotation behavior ( 24 ).…”

Section: Discussionmentioning

confidence: 81%

“…We have introduced a multitracer microPET evaluation to clarify the exact status of SND during long term follow-up ( 12 ). MicroPET scanning is a non-invasive imaging method.…”

Section: Discussionmentioning

confidence: 99%

“…It is therefore necessary to develop a new model that better mimics SND. We previously showed that SND is well characterized by microPET, using the tracers 2-deoxy-2-[ 18 F]-fluoro-D-glucose ([ 18 F]-FDG) and [ 18 F]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane ([ 18 F]-FP-CIT) ( 12 ). In this study, we propose a new rat model of SND that is generated by simultaneous injection of 6-OHDA into the MFB and QA into the ipsilateral striatum.…”

Section: Introductionmentioning

confidence: 99%

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A Rat Model of Striatonigral Degeneration Generated by Simultaneous Injection of 6-Hydroxydopamine into the Medial Forebrain Bundle and Quinolinic Acid into the Striatum

et al. 2014

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A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.

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“…Behavior tests including rotarod, beam, and air-righting reflex tests have been used to objectively determine balance in a mouse model of vestibular disorder [5, 6]. The rotarod test is also used to determine balance and coordinate movement in mice with central nervous disorders including cerebellar ataxia [7], multiple system atrophy (MSA) [8], and parkinsonism [9]. To our knowledge, however, there is no information about impaired cVEMP in a mouse model of vestibular disorder, while only three previous studies have succeeded in showing impairments of cVEMP in guinea pigs treated with gentamicin [10–12].…”

Section: Introductionmentioning

confidence: 99%

cVEMP correlated with imbalance in a mouse model of vestibular disorder

Negishi-Oshino

Ohgami

et al. 2019

Environ Health Prev Med

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Background Cervical vestibular evoked myogenic potential (cVEMP) testing is a strong tool that enables objective determination of balance functions in humans. However, it remains unknown whether cVEMP correctly expresses vestibular disorder in mice. Objective In this study, correlations of cVEMP with scores for balance-related behavior tests including rotarod, beam, and air-righting reflex tests were determined in ICR mice with vestibular disorder induced by 3,3′-iminodipropiontrile (IDPN) as a mouse model of vestibular disorder. Methods Male ICR mice at 4 weeks of age were orally administered IDPN in saline (28 mmol/kg body weight) once. Rotarod, beam crossing, and air-righting reflex tests were performed before and 3–4 days after oral exposure one time to IDPN to determine balance functions. The saccule and utricles were labeled with fluorescein phalloidin. cVEMP measurements were performed for mice in the control and IDPN groups. Finally, the correlations between the scores of behavior tests and the amplitude or latency of cVEMP were determined with Spearman’s rank correlation coefficient. Two-tailed Student’s t test and Welch’s t test were used to determine a significant difference between the two groups. A difference with p < 0.05 was considered to indicate statistical significance. Results After oral administration of IDPN at 28 mmol/kg, scores of the rotarod, beam, and air-righting reflex tests in the IDPN group were significantly lower than those in the control group. The numbers of hair cells in the saccule, utricle, and cupula were decreased in the IDPN group. cVEMP in the IDPN group was significantly decreased in amplitude and increased in latency compared to those in the control group. cVEMP amplitude had significant correlations with the numbers of hair cells as well as scores for all of the behavior tests in mice. Conclusions This study demonstrated impaired cVEMP and correlations of cVEMP with imbalance determined by behavior tests in a mouse model of vestibular disorder. Electronic supplementary material The online version of this article (10.1186/s12199-019-0794-8) contains supplementary material, which is available to authorized users.

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Evaluation of a multiple system atrophy model in rats using multitracer microPET

Cited by 4 publications

References 18 publications

Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

A Rat Model of Striatonigral Degeneration Generated by Simultaneous Injection of 6-Hydroxydopamine into the Medial Forebrain Bundle and Quinolinic Acid into the Striatum

cVEMP correlated with imbalance in a mouse model of vestibular disorder

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