scholarly journals Quantitative Gradient Echo MRI Identifies Dark Matter as a New Imaging Biomarker of Neurodegeneration that Precedes Tissue Atrophy in Early Alzheimer Disease

2021 ◽  
Author(s):  
Satya V.V.N. Kothapalli ◽  
Tammie L. Benzinger ◽  
Andrew. J. Aschenbrenner ◽  
Richard. J. Perrin ◽  
Charles. F. Hildebolt ◽  
...  
Keyword(s):  
Dark Matter ◽  
Alzheimer Disease ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Imaging Biomarker ◽  
Control Group ◽  
Histopathological Study ◽  
In Vivo Evaluation ◽  
Preclinical Ad

AbstractBackgroundCurrently, brain tissue atrophy serves as in vivo MRI biomarker of neurodegeneration in Alzheimer Disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that loss of memory in AD begins when neurons and synapses are lost. Therefore, in vivo detection of neuronal loss prior to detectable atrophy in MRI is essential for early AD diagnosis.ObjectiveTo apply a recently developed quantitative Gradient Recalled Echo (qGRE) MRI technique for in vivo evaluation of neuronal loss in human hippocampus.MethodsSeventy participants were recruited from the Knight Alzheimer Disease Research Center, representing three groups: Healthy controls [Clinical Dementia Rating® (CDR®)=0, amyloid β (Aβ)-negative), n=34]; Preclinical AD (CDR=0, Aβ-positive, n=19); and mild AD (CDR=0.5 or 1, Aβ-positive, n=17).ResultsIn hippocampal tissue, qGRE identified two types of regions: one, practically devoid of neurons, we designate as “Dark Matter”, the other, with relatively preserved neurons - “Viable Tissue”. Data showed a greater loss of neurons than defined by atrophy in the mild AD group compared with the healthy control group - neuronal loss ranged between 31% and 43% while volume loss ranged only between 10% and 19%. The concept of Dark Matter was confirmed with histopathological study of one participant who underwent in vivo qGRE 14 months prior to expiration.Conclusionin vivo qGRE method identifies neuronal loss that is associated with impaired AD-related cognition but is not recognized by MRI measurements of tissue atrophy, therefore providing new biomarkers for early AD detection.

scholarly journals Quantitative Gradient Echo MRI Identifies Dark Matter as a New Imaging Biomarker of Neurodegeneration that Precedes Tisssue Atrophy in Early Alzheimer’s Disease

2021 ◽  
pp. 1-20
Author(s):  
Satya V.V.N. Kothapalli ◽  
Tammie L. Benzinger ◽  
Andrew J. Aschenbrenner ◽  
Richard J. Perrin ◽  
Charles F. Hildebolt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dark Matter ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Imaging Biomarker ◽  
Control Group ◽  
Histopathological Study ◽  
Preclinical Ad

Background: Currently, brain tissue atrophy serves as an in vivo MRI biomarker of neurodegeneration in Alzheimer’s disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that loss of memory in AD begins when neurons and synapses are lost. Therefore, in vivo detection of neuronal loss prior to detectable atrophy in MRI is essential for early AD diagnosis. Objective: To apply a recently developed quantitative Gradient Recalled Echo (qGRE) MRI technique for in vivo evaluation of neuronal loss in human hippocampus. Methods: Seventy participants were recruited from the Knight Alzheimer Disease Research Center, representing three groups: Healthy controls [Clinical Dementia Rating® (CDR®) = 0, amyloid β (Aβ)-negative, n = 34]; Preclinical AD (CDR = 0, Aβ-positive, n = 19); and mild AD (CDR = 0.5 or 1, Aβ-positive, n = 17). Results: In hippocampal tissue, qGRE identified two types of regions: one, practically devoid of neurons, we designate as “Dark Matter”, and the other, with relatively preserved neurons, “Viable Tissue”. Data showed a greater loss of neurons than defined by atrophy in the mild AD group compared with the healthy control group; neuronal loss ranged between 31% and 43%, while volume loss ranged only between 10% and 19%. The concept of Dark Matter was confirmed with histopathological study of one participant who underwent in vivo qGRE 14 months prior to expiration. Conclusion: In vivo qGRE method identifies neuronal loss that is associated with impaired AD-related cognition but is not recognized by MRI measurements of tissue atrophy, therefore providing new biomarkers for early AD detection.

scholarly journals The In vivo evaluation of anticryptosporidiosis activity of the methanolic extract of the plant Umbilicus rupestris

2019 ◽  
Vol 20 (12) ◽  
Author(s):  
AFAF BENHOUDA ◽  
DJAHIDA BENHOUDA ◽  
MASSINISSA YAHIA
Keyword(s):  
Methanolic Extract ◽  
Activity Level ◽  
Female Rats ◽  
Control Group ◽  
Histopathological Study ◽  
In Vivo Evaluation ◽  
Group I ◽  
Cryptosporidium Oocysts ◽  
Experimental Group

Abstract. Benhouda A, Benhouda D, Yahia M. 2019. In vivo evaluation of anticryptosporidiosis activity of the methanolic extract of the plant Umbilicus rupestris. Biodiversitas 20: 3478-3483. Umbilicus rupestris (Crassulaceae) is a medicinal plant used in general traditional medicine to cure inflammation and irritation of the skin. The present research is aimed to evaluate the antiparasitic activity of the methanolic extract of the plant URMeOH of U. rupestris against the Cryptosporidium infection in immunocompetent and immunosuppressed rats experimentally infected. Twenty-one female rats were divided into two groups. Control group (group I) and experimental group (Group II). The group I was further divided into three equal groups (normal group infected and immunosuppressed infected group). The experimental group was divided into two immunosuppressed and four equal groups and two immunocompetent infected. Cryptosporidium oocysts were isolated from bovine species stools and used to infect rats. Experimental subgroups received URMeOH two as dose 100mg/kg b.w. and 200 mg/kg b.w. and continued until 15 days. Two weeks after the administration of URMeOH, feces of rats were examined for the detection of Cryptosporidium oocysts by Ziehl-Neelsen and immunofluorescence techniques, the animals were sacrificed; their small intestines were processed and examined for the detection of pathological lesions after histopathological study. In addition, the activity of myeloperoxidase (MPO) was measured in sections of the jejunum. Concerned the results, we observed a statistically significant (P<0.001) increase in the number of oocysts of Cryptosporidium in the stool for sub infected immunosuppressed groups and an increase of MPO activity compared to the corresponding subgroups immunocompetent subgroups. The URMeOH could remove Cryptosporidium oocysts from feces and intestinal sections subgroup infected immunocompetent rats receiving URMeOH. Moreover, the oocysts were significantly reduced in all other subgroups experimental infected compared to infected control subgroups. Intestinal sections in all subgroups received URMeOH revealed a more or less normal architecture. In addition, the reduction of MPO activity level was also detected in all experimental subgroups.

scholarly journals In vivo evaluation of a recombinant N-acylhomoserine lactonase formulated in a hydrogel using a murine model infected with MDR Pseudomonas aeruginosa clinical isolate, CCASUP2

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masarra M. Sakr ◽  
Walid F. Elkhatib ◽  
Khaled M. Aboshanab ◽  
Eman M. Mantawy ◽  
Mahmoud A. Yassien ◽  
...  
Keyword(s):  
Survival Rate ◽  
Murine Model ◽  
Histopathological Examination ◽  
Healing Process ◽  
Bacterial Count ◽  
Treated Group ◽  
Control Group ◽  
In Vivo Evaluation ◽  
Systemic Spread

AbstractFailure in the treatment of P. aeruginosa, due to its broad spectrum of resistance, has been associated with increased patient mortality. One alternative approach for infection control is quorum quenching which was found to decrease virulence of such pathogen. In this study, the efficiency of a recombinant Ahl-1 lactonase formulated as a hydrogel was investigated to control the infection of multidrug resistant (MDR) P. aeruginosa infected burn using a murine model. The recombinant N-acylhomoserine lactonase (Ahl-1) was formulated as a hydrogel. To test its ability to control the infection of MDR P. aeruginosa, a thermal injury model was used. Survival rate, and systemic spread of the infection were evaluated. Histopathological examination of the animal dorsal skin was also done for monitoring the healing and cellular changes at the site of infection. Survival rate in the treated group was 100% relative to 40% in the control group. A decrease of up to 3 logs of bacterial count in the blood samples of the treated animals relative to the control group and a decrease of up to 4 logs and 2.3 logs of bacteria in lung and liver samples, respectively were observed. Histopathological examination revealed more enhanced healing process in the treated group. Accordingly, by promoting healing of infected MDR P. aeruginosa burn and by reducing systemic spread of the infection as well as decreasing mortality rate, Ahl-1 hydrogel application is a promising strategy that can be used to combat and control P. aeruginosa burn infections.

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

scholarly journals Imaging Amyloid-β Deposits In Vivo

2002 ◽  
Vol 22 (9) ◽  
pp. 1035-1041 ◽  
Author(s):  
Brian J. Bacskai ◽  
William E. Klunk ◽  
Chester A. Mathis ◽  
Bradley T. Hyman
Keyword(s):  
Single Photon ◽  
Senile Plaques ◽  
Photon Emission ◽  
Multiphoton Microscopy ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
High Sensitivity ◽  
Emission Computed Tomography ◽  
Tissue Samples

Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-β plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-β plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-β deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-β deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-β with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques.

In Vivo Evaluation of Micronucleus Frequencies in Buccal Mucosal Cells of Orthodontic Patients with and Without Fluoride Use

2021 ◽  
pp. 030157422110373
Author(s):  
Prasad Chitra ◽  
GS Prashantha ◽  
Arun Rao ◽  
Harshvardhan S Jois
Keyword(s):  
Metal Ion ◽  
Orthodontic Treatment ◽  
Biological Tissues ◽  
Control Group ◽  
Time Interval ◽  
Ion Release ◽  
In Vivo Evaluation ◽  
Metal Ion Release ◽  
Mucosal Cells

Introduction: Fluoride agents to prevent white spot lesions are used often during orthodontic treatment. The beneficial effects of fluoride, when consumed within permissible limits on dental structures, are well known. Their implications on underlying biological tissues, however, are unknown. Mouthwashes and dentifrices with fluorides are associated with metal ion release into the mouth with possible cell genotoxicity. Since these cariostatic agents are frequently used during orthodontic therapy, a deeper understanding of the effects of fluoride on oral tissues was considered necessary. Methodology: Three groups of patients (30 each)—group 1 (untreated controls), group 2 (non-fluoridated), and group 3 (Fluoridated) were analyzed. Patients in groups 2 and 3 were bonded with the same bracket prescription and treated with similar archwire sequences. Buccal mucosal cells at 4 specific time periods (before treatment, 1 week, 30 days, and 6 months) were collected, using a wooden tongue depressor, and assessed for any nuclear abnormalities. Comparisons of changes were made with an untreated control group and also between the non-fluoridated and fluoridated groups. Relevant conclusions were drawn after analysis of the results. Results: Greater number of nuclei were observed at the 30-day time interval in the fluoridated group, which was statistically significant at P < .001. Conclusion: Use of fluoridated oral hygiene products in patients undergoing fixed orthodontic treatment with NiTi archwires could increase the risk of micronuclei formation in buccal mucosal cells.

scholarly journals Development and Optimization of a Fluorescent Imaging System to Detect Amyloid-β Proteins: Phantom Study

2018 ◽  
Vol 9 ◽  
pp. 117959721878108 ◽  
Author(s):  
David Tes ◽  
Karl Kratkiewicz ◽  
Ahmed Aber ◽  
Luke Horton ◽  
Mohsin Zafar ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Imaging System ◽  
Ex Vivo ◽  
Amyloid Β ◽  
The United States ◽  
Fluorescent Imaging ◽  
Fluorescent Properties ◽  
In Vivo Experiments ◽  
The Brain

Alzheimer disease is the most common form of dementia, affecting more than 5 million people in the United States. During the progression of Alzheimer disease, a particular protein begins to accumulate in the brain and also in extensions of the brain, ie, the retina. This protein, amyloid-β (Aβ), exhibits fluorescent properties. The purpose of this research article is to explore the implications of designing a fluorescent imaging system able to detect Aβ proteins in the retina. We designed and implemented a fluorescent imaging system with a range of applications that can be reconfigured on a fluorophore to fluorophore basis and tested its feasibility and capabilities using Cy5 and CRANAD-2 imaging probes. The results indicate a promising potential for the imaging system to be used to study the Aβ biomarker. A performance evaluation involving ex vivo and in vivo experiments is planned for future study.

Effect of Arecoline on Regeneration of Injured Peripheral Nerves

2013 ◽  
Vol 41 (04) ◽  
pp. 865-885 ◽  
Author(s):  
Sheng-Chi Lee ◽  
Chin-Chuan Tsai ◽  
Chun-Hsu Yao ◽  
Yuan-Man Hsu ◽  
Yueh-Sheng Chen ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
In Vitro Study ◽  
Control Group ◽  
Neural Cells ◽  
In Vivo Evaluation

The present study provides in vitro and in vivo evaluation of arecoline on peripheral nerve regeneration. In the in vitro study, we found that arecoline at 50 μg/ml could significantly promote the survival and outgrowth of cultured Schwann cells as compared to the controls treated with culture medium only. In the in vivo study, we evaluated peripheral nerve regeneration across a 10-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve chamber filled with the arecoline solution. In the control group, the chambers were filled with normal saline only. At the end of the fourth week, morphometric data revealed that the arecoline-treated group at 5 μg/ml significantly increased the number and the density of myelinated axons as compared to the controls. Immunohistochemical staining in the arecoline-treated animals at 5 μg/ml also showed their neural cells in the L4 and L5 dorsal root ganglia ipsilateral to the injury were strongly retrograde-labeled with fluorogold and lamina I–II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled compared with the controls. In addition, we found that the number of macrophages recruited in the distal sciatic nerve was increased as the concentration of arecoline was increased. Electrophysiological measurements showed the arecoline-treated groups at 5 and 50 μg/ml had a relatively larger nerve conductive velocity of the evoked muscle action potentials compared to the controls. These results indicate that arecoline could stimulate local inflammatory conditions, improving the recovery of a severe peripheral nerve injury.

scholarly journals Insights into smouldering MS brain pathology with multimodal diffusion tensor and PET imaging

2020 ◽  
Author(s):  
Svetlana Bezukladova ◽  
Jouni Tuisku ◽  
Markus Matilainen ◽  
Anna Vuorimaa ◽  
Marjo Nylund ◽  
...  
Keyword(s):  
White Matter ◽  
Pet Imaging ◽  
Microglial Activation ◽  
Diffusion Tensor ◽  
Volume Ratio ◽  
Translocator Protein ◽  
Control Group ◽  
In Vivo Evaluation ◽  
Conventional Mri

Objective: To evaluate in vivo the co-occurrence of microglial activation and microstructural white matter damage in multiple sclerosis (MS) brain, and to examine their association with clinical disability. Methods: 18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [11C](R)-PK11195. TSPO-binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images. Diffusion tensor imaging (DTI) and conventional MRI were performed at the same time. Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated within the whole normal appearing white matter (NAWM) and segmented NAWM regions appearing normal in conventional MRI. 55 MS patients and 15 healthy controls were examined. Results: Microstructural damage was observed in the NAWM of MS brain. DTI parameters of MS patients were significantly altered in the NAWM, when compared to an age- and sex-matched healthy control group: mean FA was decreased, and MD, AD and RD were increased. These structural abnormalities correlated with increased TSPO binding in the whole NAWM and in the temporal NAWM (p<0.05 for all correlations; p<0.01 for RD in the temporal NAWM). Both compromised WM integrity and increased microglial activation in the NAWM correlated significantly with higher clinical disability measured with expanded disability status scale (EDSS). Conclusions: Widespread structural disruption in the NAWM is linked to neuroinflammation, and both phenomena associate with clinical disability. Multimodal PET and DTI imaging allows in vivo evaluation of widespread MS pathology not visible using conventional MRI.

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