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

2020 ◽  
pp. 1-8
Author(s):  
Bo Ning ◽  
Gongbo Guo ◽  
Chunming Gu ◽  
Jiadi Xu ◽  
Adnan Bibic ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Mouse Model ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Brain Regions ◽  
Motor Impairments ◽  
Pial Arteries ◽  
Male And Female ◽  
Lrrk2 G2019s ◽  
Mri Scans

<b><i>Background:</i></b> Parkinson’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. <b><i>Objectives:</i></b> To 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. <b><i>Methods:</i></b> Anatomical 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. <b><i>Results:</i></b> Compared 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. <b><i>Conclusions:</i></b> Alterations 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.

Measurement of cerebral blood volume in mouse brain regions using micro-computed tomography

NeuroImage ◽  
2009 ◽  
Vol 47 (4) ◽  
pp. 1312-1318 ◽  
Author(s):  
Brige P. Chugh ◽  
Jason P. Lerch ◽  
Lisa X. Yu ◽  
Martin Pienkowski ◽  
Robert V. Harrison ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Blood Volume ◽  
Mouse Brain ◽  
Cerebral Blood Volume ◽  
Brain Regions ◽  
Micro Computed Tomography

Microvascular cerebral blood volume changes in aging APPswe/PS1dE9 AD mouse model: a voxel-wise approach

2012 ◽  
Vol 218 (5) ◽  
pp. 1085-1098 ◽  
Author(s):  
Valerio Zerbi ◽  
Diane Jansen ◽  
Pieter J. Dederen ◽  
Andor Veltien ◽  
Bob Hamans ◽  
...  
Keyword(s):  
Mouse Model ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Volume Changes ◽  
Ad Mouse Model

scholarly journals Cerebral Blood Flow, Blood Volume, and Mean Transit Time Responses to Propofol and Indomethacin in Peritumor and Contralateral Brain Regions

2010 ◽  
Vol 112 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Mads Rasmussen ◽  
Niels Juul ◽  
Søren M. Christensen ◽  
Kristjana Y. Jónsdóttir ◽  
Carsten Gyldensted ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Tumors ◽  
Blood Volume ◽  
Transit Time ◽  
Gray Matter ◽  
Cerebral Blood Volume ◽  
Mean Transit Time ◽  
Brain Regions ◽  
Normal Brain

Background The regional cerebral blood flow (CBF) response to propofol and indomethacin may be abnormal in patients with brain tumors. First, the authors tested the hypothesis that during propofol anesthesia alone and combined with indomethacin, changes in CBF, cerebral blood volume (CBV), and plasma mean transit time (MTT) differ in the peritumoral tissue compared with the contralateral normal brain region. Second, the authors tested the hypothesis that CBF and CBV are reduced and MTT is prolonged, in both regions during propofol anesthesia and indomethacin administration compared with propofol alone. Methods The authors studied eight patients subjected to craniotomy under propofol-fentanyl anesthesia for supratentorial brain tumors. Magnetic resonance imaging, including perfusion- and diffusion-weighted and structural sequences, was performed (1) on the day before surgery, (2) before and (3) after administration of indomethacin in the propofol-fentanyl anesthetized patient, and (4) 2 days after surgery. Maps of CBF, CBV, and MTT were calculated. The regions of interest were peritumoral gray matter and opposite contralateral gray matter. Analysis of variance was used to analyze flow data. Results Propofol anesthesia was associated with a median 32% (range, 3-61%) and 47% (range, 17-67%) reduction in CBF in the peritumoral and contralateral regions, respectively.The interaction between intervention with propofol and indomethacin and region of interest was not significant for any flow modalities. Neither intervention nor region was significant for MTT, CBF, and CBV (P &gt; 0.05). Conclusion The CBF, CBV, and MTT responses to propofol and indomethacin are not different in the peritumoral region compared with contralateral brain tissue. Indomethacin did not further influence regional CBF, CBV, and MTT during propofol anesthesia.

scholarly journals Cerebral haemodynamics during simulated driving: Changes in workload are detectable with functional near infrared spectroscopy

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248533
Author(s):  
Peter M. Bloomfield ◽  
Hayden Green ◽  
Nicholas Gant
Keyword(s):  
Prefrontal Cortex ◽  
Infrared Spectroscopy ◽  
Blood Volume ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Cerebral Blood Volume ◽  
Cortical Activity ◽  
Medial Aspect ◽  
Functional Near Infrared Spectroscopy ◽  
Simulated Driving

Motor vehicle operation is a complicated task and substantial cognitive resources are required for safe driving. Experimental paradigms examining cognitive workload using driving simulators often introduce secondary tasks, such as mathematical exercises, or utilise simulated in-vehicle information systems. The effects of manipulating the demands of the primary driving task have not been examined in detail using advanced neuroimaging techniques. This study used a manipulation of the simulated driving environment to test the impact of increased driving complexity on brain activity. Fifteen participants drove in two scenarios reflecting common driving environments differing in the amount of vehicular traffic, frequency of intersections, number of buildings, and speed limit restrictions. Functional near infrared spectroscopy was used to quantify changes in cortical activity; fifty-five optodes were placed over the prefrontal and occipital cortices, commonly assessed areas during driving. Compared to baseline, both scenarios increased oxyhaemoglobin in the bilateral prefrontal cortex and cerebral blood volume in the right prefrontal cortex (all p ≤ 0.05). Deoxyhaemoglobin decreased at the bilateral aspects of the prefrontal cortex but overall tended to increase in the medial aspect during both scenarios (both p ≤ 0.05). Cerebral oxygen exchange significantly declined at the lateral aspects of the prefrontal cortex, with a small but significant increase seen in the medial aspect (both p < 0.05). There were no significant differences for oxyhaemoglobin, deoxyhaemoglobin, or cerebral blood volume (all p > 0.05). This study demonstrates that functional near infrared spectroscopy is capable of detecting changes in cortical activity elicited by simulated driving tasks but may be less sensitive to variations in driving workload aggregated over a longer duration.

scholarly journals Sexually dimorphic neuroanatomical differences relate to ASD-relevant behavioral outcomes in a maternal autoantibody mouse model

2021 ◽  
Author(s):  
Matthew R. Bruce ◽  
Karen L. Jones ◽  
Anthony C. Vernon ◽  
Jill L. Silverman ◽  
Jacqueline N. Crawley ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Volume ◽  
Brain Size ◽  
Ex Vivo ◽  
Fetal Brain ◽  
Brain Regions ◽  
Prenatally Exposed ◽  
Total Brain Volume ◽  
Male And Female ◽  
Peptide Epitopes

AbstractImmunoglobulin G (IgG) autoantibodies reactive to fetal brain proteins in mothers of children with ASD have been described by several groups. To understand their pathologic significance, we developed a mouse model of maternal autoantibody related ASD (MAR-ASD) utilizing the peptide epitopes from human autoantibody reactivity patterns. Male and female offspring prenatally exposed to the salient maternal autoantibodies displayed robust deficits in social interactions and increased repetitive self-grooming behaviors as juveniles and adults. In the present study, neuroanatomical differences in adult MAR-ASD and control offspring were assessed via high-resolution ex vivo magnetic resonance imaging (MRI) at 6 months of age. Of interest, MAR-ASD mice displayed significantly larger total brain volume and of the 159 regions examined, 31 were found to differ significantly in absolute volume (mm3) at an FDR of <5%. Specifically, the absolute volumes of several white matter tracts, cortical regions, and basal nuclei structures were significantly increased in MAR-ASD animals. These phenomena were largely driven by female MAR-ASD offspring, as no significant differences were seen with either absolute or relative regional volume in male MAR-ASD mice. However, structural covariance analysis suggests network-level desynchronization in brain volume in both male and female MAR-ASD mice. Additionally, preliminary correlational analysis with behavioral data relates that volumetric increases in numerous brain regions of MAR-ASD mice were correlated with social interaction and repetitive self-grooming behaviors in a sex-specific manner. These results demonstrate significant sex-specific effects in brain size, regional relationships, and behavior for offspring prenatally exposed to MAR-ASD autoantibodies relative to controls.

scholarly journals Gender Related Changes in Gene Expression Induced by Valproic Acid in A Mouse Model of Autism and the Correction by S-adenosyl Methionine. Does It Explain the Gender Differences in Autistic Like Behavior?

2019 ◽  
Vol 20 (21) ◽  
pp. 5278 ◽  
Author(s):  
Liza Weinstein-Fudim ◽  
Zivanit Ergaz ◽  
Gadi Turgeman ◽  
Joseph Yanai ◽  
Moshe Szyf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gender Differences ◽  
Valproic Acid ◽  
Prefrontal Cortex ◽  
Mouse Model ◽  
Behavioral Changes ◽  
Male And Female ◽  
Female Mice ◽  
Adenosyl Methionine ◽  
Males And Females

In previous studies we produced autism like behavioral changes in mice by Valproic acid (VPA) with significant differences between genders. S-adenosine methionine (SAM) prevented the autism like behavior in both genders. The expression of 770 genes of pathways involved in neurophysiology and neuropathology was studied in the prefrontal cortex of 60 days old male and female mice using the NanoString nCounter. In females, VPA induced statistically significant changes in the expression of 146 genes; 71 genes were upregulated and 75 downregulated. In males, VPA changed the expression of only 19 genes, 16 were upregulated and 3 downregulated. Eight genes were similarly changed in both genders. When considering only the genes that were changed by at least 50%, VPA changed the expression of 15 genes in females and 3 in males. Only Nts was similarly downregulated in both genders. SAM normalized the expression of most changed genes in both genders. We presume that genes that are involved in autism like behavior in our model were similarly changed in both genders and corrected by SAM. The behavioral and other differences between genders may be related to genes that were differently affected by VPA in males and females and/or differently affected by SAM.

scholarly journals Enhanced Cerebral Blood Volume under Normobaric Hyperoxia in the J20-hAPP Mouse Model of Alzheimer’s Disease

2019 ◽  
Author(s):  
Osman Shabir ◽  
Paul Sharp ◽  
Monica A Rebollar ◽  
Luke Boorman ◽  
Clare Howarth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Blood Volume ◽  
Neural Activity ◽  
Cerebral Blood Volume ◽  
Neurovascular Coupling ◽  
Cranial Window ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

AbstractEarly impairments to neurovascular coupling have been proposed to be a key pathogenic factor in the onset and progression of Alzheimer’s disease (AD). Studies have shown impaired neurovascular function in several mouse models of AD, including the J20-hAPP mouse. In this study, we aimed to investigate early neurovascular changes using wild-type (WT) controls and J20-hAPP mice at 6-9 months of age, by measuring cerebral haemodynamics and neural activity to physiological sensory stimulations. A thinned cranial window was prepared to allow access to cortical vasculature and imaged using 2D-optical imaging spectroscopy (2D-OIS). After chronic imaging sessions where the skull was intact, a terminal acute imaging session was performed where an electrode was inserted into the brain to record simultaneous neural activity. We found that cerebral haemodynamic changes were significantly enhanced in J20-hAPP mice compared with controls in response to physiological stimulations, potentially due to the significantly higher neural activity (hyperexcitability) seen in the J20-hAPP mice. Thus, neurovascular coupling remained preserved under a chronic imaging preparation. Further, under hyperoxia, the baseline blood volume and saturation of all vascular compartments in the brains of J20-hAPP mice were substantially enhanced compared to WT controls, but this effect disappeared under normoxic conditions. This study highlights novel findings not previously seen in the J20-hAPP mouse model, and may point towards a potential therapeutic strategy by driving an increased baseline blood flow to the brain, thereby potentially enhancing the clearance of beta-amyloid.

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