Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

Fang, Yuan; Dong, Yanchao; Zheng, Tao; Du, Dan; Wen, Jiexia; Gao, Dawei; Liu, Lanxiang

doi:10.3389/fnins.2017.00409

Cited by 7 publications

(7 citation statements)

References 34 publications

(42 reference statements)

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“…Nevertheless, the half-life T 1/2 was significantly prolonged due to the granulomatous wall limitation. Fang et al (2017) used the tracer-based MRI method to explore the pathological changes of ECS in Parkinson's disease rats and reached a similar conclusion: Due to the necrosis of dopamine neurons, the tortuosity of ECS at the substantia nigra of PD rats decreased, and the diffusion coefficient increased. However, accumulated neuronal metabolic waste produced by PD rats will hinder the drainage of ISF, resulting in the prolongation of half-life.…”

Section: Discussionmentioning

confidence: 84%

Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer

et al. 2022

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PurposeThis study aimed to investigate the changes in extracellular space (ECS) in cryptococcal brain granuloma and its pathological mechanism.Materials and methodsThe animal model of cryptococcal brain granuloma was established by injecting 1 × 106 CFU/ml of Cryptococcus neoformans type A suspension into the caudate nucleus of Sprague–Dawley rats with stereotactic technology. The infection in the brain was observed by conventional MRI scanning on days 14, 21, and 28 of modeling. The tracer-based MRI with a gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a magnetic tracer was performed on the rats with cryptococcal granuloma and the rats in the control group. The parameters of ECS in each area of cryptococcal brain granuloma were measured. The parameters of ECS in the two groups were compared by independent sample t-test, and the changes in ECS and its mechanism were analyzed.ResultsUp to 28 days of modeling, the success rate of establishing the brain cryptococcal granuloma model with 1 × 106 CFU/ml Cryptococcus neoformans suspension was 60%. In the internal area of cryptococcal granuloma, the effective diffusion coefficient D* was significantly higher than that of the control group (t = 2.76, P < 0.05), and the same trend showed in the volume ratio α (t = 3.71, P < 0.05), the clearance rate constant k (t = 3.137, P < 0.05), and the tracer half-life T1/2 (t = 3.837, P < 0.05). The tortuosity λ decreased compared with the control group (t = −2.70, P < 0.05). At the edge of the cryptococcal granuloma, the D* and α decreased, while the λ increased compared with the control group (D*:t = −6.05, P < 0.05; α: t = −4.988, P < 0.05; λ: t = 6.222, P < 0.05).ConclusionThe internal area of the lesion demonstrated a quicker, broader, and more extended distribution of the tracer, while the edge of the lesion exhibited a slower and narrower distribution. MRI tracer method can monitor morphological and functional changes of ECS in pathological conditions and provide a theoretical basis for the treatment via ECS.

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Section: Discussionmentioning

confidence: 84%

Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer

et al. 2022

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“…These results showed that the stability of the mitochondrial membrane potential was a prerequisite for maintaining normal mitochondrial function, and the decreased membrane potential led to mitochondrial dysfunction, which was an important feature of early apoptosis ( Zamzami et al, 2005 ). Another study showed that LITUS could slow the depolarization of mitochondrial membrane potential that was induced by exposure to toxic substances and inhibit cell apoptosis ( Fang et al, 2017 ). This effect of LITUS could occur because LITUS restored the mitochondrial membrane potential and ensured normal mitochondrial function that improved the oxidative stress induced by toxic substances and inhibited cell apoptosis in the dopaminergic neurons ( Karmacharya et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Rats were randomly divided into two groups: (1) a hemi-PD group ( n = 10) and (2) a LITUS group ( n = 10). The surgical procedures and rotation test that were used for induction and assessment of the PD model followed the published protocols by Fang et al; all 20 rats were subjected to the modeling process ( Fang et al, 2017 ). First, the rat was anesthetized using 10% chloral hydrate by intraperitoneal injection, initial measurement was 3 ml/kg, and maintained dose was 2 ml/kg/h for the duration of the operation.…”

Section: Methodsmentioning

confidence: 99%

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Assessment of Neuroprotective Effects of Low-Intensity Transcranial Ultrasound Stimulation in a Parkinson’s Disease Rat Model by Fractional Anisotropy and Relaxation Time T2∗ Value

et al. 2021

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Background: Low-intensity transcranial ultrasound (LITUS) may have a therapeutic effect on Parkinson’s disease (PD) patients to some extent. Fractional anisotropy (FA) and relaxation time T2∗ that indicate the integrity of fiber tracts and iron concentrations in brain tissue have been used to evaluate the therapeutic effects of LITUS.Purpose: This study aims to use FA and T2∗ values to evaluate the therapeutic effects of LITUS in a PD rat model.Materials and Methods: Twenty Sprague-Dawley rats were randomly divided into a hemi-PD group (n = 10) and a LITUS group (n = 10). Single-shot spin echo echo-planar imaging and fast low-angle shot T2WI sequences at 3.0 T were used. The FA and T2∗ values on the right side of the substantia nigra (SN) pars compacta were measured to evaluate the therapeutic effect of LITUS in the rats.Results: One week after PD-like signs were induced in the rats, the FA value in the LITUS group was significantly larger compared with the PD group (0.214 ± 0.027 vs. 0.340 ± 0.032, t = 2.864, P = 0.011). At the 5th and 6th weeks, the FA values in the LITUS group were significantly smaller compared with the PD group (5th week: 0.290 ± 0.037 vs. 0.405 ± 0.027, t = 2.385, P = 0.030; 6th week: 0.299 ± 0.021 vs. 0.525 ± 0.028, t = 6.620, P < 0.0001). In the 5th and 6th weeks, the T2∗ values in the injected right SN of the LITUS group were significantly higher compared with the PD group (5th week, 12.169 ± 0.826 in the LITUS group vs. 7.550 ± 0.824 in the PD group; 6th week, 11.749 ± 0.615 in the LITUS group vs. 7.550 ± 0.849 in the PD group).Conclusion: LITUS had neuroprotective effects and can reduce the damage of 6-OHDA-induced neurotoxicity in hemi-PD rats. The combination of FA and T2∗ assessments can potentially serve as a new and effective method to evaluate the therapeutic effects of LITUS.

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“…Brain lymphatics associated with glymphatic(58, 70,122) were found to clear extra amount of materials produced on-site in the brain as well as materials transported in from the blood ( Figure 10B). These materials include exosomes, and if exosomes carry modified abnormal proteins such as abnormal tau (23,73,123) or alphasynuclein, (24,74,124) they could be the vehicle of clearance of those abnormal proteins. Even extracellular amyloid could be cleared without or within exosomes.…”

Section: Specificity Of Exosomes Uptake and Therapeutic Effectsmentioning

confidence: 99%

Physiologic constraints of using exosomes in vivo as systemic delivery vehicles

Lee

Suh

Kang

et al. 2019

PRNANO

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Systemic delivery of exosomes meets hurdles which had not been elucidated using live molecular imaging for their biodistribution. Production and uptake of endogenous exosomes are expected to be nonspecific and specific, respectively, where external stimuli of production of exosomes and their quantitative degree of productions are not understood. Despite this lack of understanding of basic physiology of in vivo behavior of exosomes including their possible paracrine or endocrine actions, many engineering efforts are taken to develop therapeutic vehicles. Especially, the fraction of exosomes’ taking the routes of waste disposal and exerting target actions are not characterized after systemic administration. Here, we reviewed the literature about in vivo distribution and disposal/excretion of exogenous or endogenous exosomes and, from these limited resources of knowledge currently available, summarized the knowledge and the uncertainties of exosomes on physiologic standpoints. An eloquent example of the investigations to understand the roles and confounders of exosomes’ action in the brain was highlighted with emphasis on the recent discovery of brain lymphatics and hypothesis of glymphatic/lymphatic clearance pathways in diseases as well as in physiologic processes. The possibility of delivering therapeutic exosomes through the systemic circulation, across blood-brain barriers and finally to target cells such as microglia, astrocytes and/or neurons is a good testbed in which the investigators can formulate problems to solve for both understanding (science) and application (engineering).

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Altered Tracer Distribution and Clearance in the Extracellular Space of the Substantia Nigra in a Rodent Model of Parkinson's Disease

Cited by 7 publications

References 34 publications

Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer

Mechanism of extracellular space changes in cryptococcal brain granuloma revealed by MRI tracer

Assessment of Neuroprotective Effects of Low-Intensity Transcranial Ultrasound Stimulation in a Parkinson’s Disease Rat Model by Fractional Anisotropy and Relaxation Time T2∗ Value

Physiologic constraints of using exosomes in vivo as systemic delivery vehicles

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