Evidence map›Paper›PMID 33152738›Full record

ArticleNeuro-degenerative diseases2020

Mutant G2019S-LRRK2 Induces Abnormalities in Arteriolar Cerebral Blood Volume in Mouse Brains: An MRI Study.

Bo Ning, Gongbo Guo, Chunming Gu, Jiadi Xu, Adnan Bibic, Xiaofei He, Hongshuai Liu, Lin Chen, Zhiliang Wei, Wenzhen Duan and 6 more

Open access · greenAbstract read
In one paragraph

Article in Neuro-degenerative diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 51% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Bo NingDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Gongbo GuoDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chunming GuDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jiadi XuDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Adnan BibicDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Xiaofei HeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hongshuai LiuDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Lin ChenDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Zhiliang WeiDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Wenzhen DuanDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Peiying LiuDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Hanzhang LuDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Peter C M van ZijlDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Christopher A RossDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Wanli SmithDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, wsmith60@jhmi.edu.
Jun HuaDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kennedy Krieger Institute · USJohns Hopkins University · US

Funding

LRRK2, KIF5A and Parkinson diseaseR01NS093383 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SMITH, WANLI W · 2016 to 2020
$2.1M
Cerebrovascular Abnormalities in Huntington's DiseaseR21NS104480 · NINDS · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI DUAN, WENZHEN, HUA, JUN · 2018 to 2019
$446k
NINDS NIH HHS R01 NS093383NINDS NIH HHS R21 NS104480
6 · The paper itself

Abstract

backgroundParkinson's disease (PD) is the second most common neurodegenerative disease and the most common movement disorder characterized by motor impairments resulting from midbrain dopamine neuron loss. Abnormalities in small pial arteries and arterioles, which are the primary pathways of local delivery of nutrients and oxygen in brain tissue, have been reported in many neurodegenerative diseases including PD. Mutations in LRRK2 cause genetic PD and contribute to sporadic PD. The most common PD-linked mutation LRRK2 G2019S contributes 20-47% of genetic forms of PD in Caucasian populations. The human LRRK2 G2019S transgenic mouse model displays PD-like movement impairment and was used to identify novel LRRK2 inhibitors, which provides a useful model for studying microvascular abnormalities in PD.

objectivesTo investigate abnormalities in arteriolar cerebral blood volume (CBVa) in various brain regions using the inflow-based vascular-space occupancy (iVASO) MRI technique in LRRK2 mouse models of PD.

methodsAnatomical and iVASO MRI scans were performed in 5 female and 7 male nontransgenic (nTg), 3 female and 4 male wild-type (WT) LRRK2, and 5 female and 7 male G2019S-LRRK2 mice of 9 months of age. CBVa was calculated and compared in the substantia nigra (SN), olfactory cortex, and prefrontal cortex.

resultsCompared to nTg mice, G2019S-LRRK2 mice showed decreased CBVa in the SN, but increased CBVa in the olfactory and prefrontal cortex in both male and female groups, whereas WT-LRRK2 mice showed no change in CBVa in the SN (male and female), the olfactory (female), and prefrontal (female) cortex, but a slight increase in CBVa in the olfactory and prefrontal cortex in the male group only.

conclusionsAlterations in the blood volume of small arteries and arterioles (CBVa) were detected in the G2019S-LRRK2 mouse model of PD. The opposite changes in CBVa in the SN and the cortex indicate that PD pathology may have differential effects in different brain regions. Our results suggest the potential value of CBVa as a marker for clinical PD studies.

Indexed as

Cerebral Blood VolumeMagnetic Resonance ImagingAnimalsArteriolesBrainDisease Models, AnimalFemaleLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiceMice, TransgenicMutationParkinson DiseaseLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanBlood vesselInflow-based vascular-space occupancyLeucine-rich repeat kinase 2Magnetic resonance imagingPerfusionSubstantia nigra

Identifiers

PMID33152738
PMCPMC7864856
OpenAlexW3095073630

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.