scholarly journals Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model–Part II: Microglia and Mitochondria

Neuroglia ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 311-326 ◽  
Author(s):  
Melvin Hayden ◽  
DeAna Grant ◽  
Annayya Aroor ◽  
Vincent DeMarco

Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. This study tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions may depict abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks), left-brain hemispheres of the DBC and age-matched nondiabetic control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We observed an attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickened basement membranes, adherent red and white blood cells, neurovascular unit microbleeds and pathologic remodeling of protoplasmic astrocytes. In this second of a three-part series, we focus on the observational ultrastructural remodeling of microglia and mitochondria in relation to the NVU in leptin receptor deficient DBC models. This study identified novel ultrastructural core signature remodeling changes, which consisted of invasive activated microglia, microglial aberrant mitochondria with nuclear chromatin condensation and adhesion of white blood cells to an activated endothelium of the NVU. In conclusion, the results implicate activated microglia in NVU uncoupling and the resulting ischemic neuronal and synaptic damage, which may be related to impaired cognition and diabetic cognopathy.

Neuroglia ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 220-244 ◽  
Author(s):  
Melvin Hayden ◽  
DeAna Grant ◽  
Annayya Aroor ◽  
Vincent DeMarco

Obesity, insulin resistance, and type 2 diabetes mellitus are associated with cognitive impairment, known as diabetic cognopathy. In this study, we tested the hypothesis that neurovascular unit(s) (NVU) within cerebral cortical gray matter regions display abnormal cellular remodeling. The monogenic (Leprdb) female diabetic db/db (BKS.CgDock7m +/+Leprdb/J; DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (at 20 weeks of age), left-brain hemispheres of the DBC and age-matched non-diabetic wild-type control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We found attenuation/loss of endothelial blood–brain barrier tight/adherens junctions and pericytes, thickening of the basement membrane, aberrant mitochondria, and pathological remodeling of protoplasmic astrocytes. Additionally, there were adherent red blood cells and NVU microbleeds (cortical layer III) in DBC mice, which were not observed in CKC animals. While this study represents only a “snapshot in time”, it does allow for cellular remodeling comparisons between DBC and CKC. In this paper, the first of a three-part series, we report the observational ultrastructural remodeling changes of the NVU and its protoplasmic astrocytes in relation to the surrounding neuropil. Having identified multiple abnormal cellular remodeling changes in the DBC as compared to CKC models, we will design future experiments to evaluate various treatment modalities in DBC mice.


Neuroglia ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 351-367 ◽  
Author(s):  
Melvin Hayden ◽  
Deana Grant ◽  
Aranyra Aroor ◽  
Vincent DeMarco

Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. In this study, we tested the hypothesis that neurovascular unit(s) (NVU), oligodendrocytes, and myelin within cerebral cortical grey matter and deeper transitional zone regions between the cortical grey matter and white matter may be abnormal. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+ Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks of age), left-brain hemispheres of the DBC and age-matched non-diabetic wild type control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We found prominent remodeling of oligodendrocytes with increased nuclear chromatin condensation and volume and increased numbers of active myelination sites of the cytoplasm in transition zones. Marked dysmyelination with outer myelin lamellae sheath splitting, separation, and ballooning with aberrant mitochondria in grey matter and similar myelin remodeling changes with marked disarray with additional axonal collapse in transitional zones in DBC as compared to CKC models.


Author(s):  
Delma P. Thomas ◽  
Dianne E. Godar

Ultraviolet radiation (UVR) from all three waveband regions of the UV spectrum, UVA (320-400 nm), UVB (290-320 nm), and UVC (200-290 nm), can be emitted by some medical devices and consumer products. Sunlamps can expose the blood to a considerable amount of UVR, particularly UVA and/or UVB. The percent transmission of each waveband through the epidermis to the dermis, which contains blood, increases in the order of increasing wavelength: UVC (10%) < UVB (20%) < UVA (30%). To investigate the effects of UVR on white blood cells, we chose transmission electron microscopy to examine the ultrastructure changes in L5178Y-R murine lymphoma cells.


1990 ◽  
Vol 63 (01) ◽  
pp. 112-121 ◽  
Author(s):  
David N Bell ◽  
Samira Spain ◽  
Harry L Goldsmith

SummaryThe effect of red blood cells, rbc, and shear rate on the ADPinduced aggregation of platelets in whole blood, WB, flowing through polyethylene tubing was studied using a previously described technique (1). Effluent WB was collected into 0.5% glutaraldehyde and the red blood cells removed by centrifugation through Percoll. At 23°C the rate of single platelet aggregtion was upt to 9× greater in WB than previously found in platelet-rich plasma (2) at mean tube shear rates Ḡ = 41.9,335, and 1,920 s−1, and at both 0.2 and 1.0 µM ADP. At 0.2 pM ADP, the rate of aggregation was greatest at Ḡ = 41.9 s−1 over the first 1.7 s mean transit time through the flow tube, t, but decreased steadily with time. At Ḡ ≥335 s−1 the rate of aggregation increased between t = 1.7 and 8.6 s; however, aggregate size decreased with increasing shear rate. At 1.0 µM ADP, the initial rate of single platelet aggregation was still highest at Ḡ = 41.9 s1 where large aggregates up to several millimeters in diameter containing rbc formed by t = 43 s. At this ADP concentration, aggregate size was still limited at Ḡ ≥335 s−1 but the rate of single platelet aggregation was markedly greater than at 0.2 pM ADP. By t = 43 s, no single platelets remained and rbc were not incorporated into aggregates. Although aggregate size increased slowly, large aggregates eventually formed. White blood cells were not significantly incorporated into aggregates at any shear rate or ADP concentration. Since the present technique did not induce platelet thromboxane A2 formation or cause cell lysis, these experiments provide evidence for a purely mechanical effect of rbc in augmenting platelet aggregation in WB.


2013 ◽  
Author(s):  
Olga Papalou ◽  
Sarantis Livadas ◽  
Athanasios Karachalios ◽  
Nektarios Benetatos ◽  
George Boutzios ◽  
...  

2014 ◽  
Vol 23 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Christos Triantos ◽  
Emmanuel Louvros ◽  
Maria Kalafateli ◽  
Anne Riddell ◽  
Ulrich Thalheimer ◽  
...  

Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet.Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 noncirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC).Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleedingbut was present in seven (23%) variceal bleeders (median levels: 0.03 u/mL (0.01-0.07)) and was quantifiable for 3 days in six of seven patients. Four of seven variceal bleeders with anti-Xa activity present had HCC (p=0.023). Age, creatinine, platelet count and total infections the second day from admission were significantly correlated with the presence of measureable anti-Xa levels (p=0.014, 0.032, 0.004 and 0.019, respectively). In the HCC group, anti-Xa activity was present in three patients (30%) [median levels: 0.05 u/mL (0.01-0.06)].Conclusions: In this study, variceal bleeders and 30% of the patients with HCC had endogenous heparinoids that were detected by a clotting based anti-Xa activity assay, whereas there was no anti Xa activity present in patients with cirrhosis without infection, or bleeding or HCC, nor in those with ulcer bleeding. Thus, the anti-Xa activity is likely to be a response to bacterial infection and/or presence of HCC in cirrhosis.List of abbreviations: AFP, alpha-fetoprotein; aPTT, activated partial thromboplastin time; CP, Child-Pugh; FXa, activated factor X; GAGS, glycosaminoglycans; Hb, hemoglobin; HCC, hepatocellular carcinoma; HVPG, hepatic venous pressure gradient; INR, International normalized ratio; LMWHs, low molecular weight heparins; MELD, Model for End-stage Liver Disease; PPP, platelet-poor plasma; PRBC, packed red blood cells; PT, prothrombin time; SBP, sponataneous bacterial peritonitis; TEG, thromboelastography; WBC, white blood cells.


2012 ◽  
Author(s):  
Erin Sandford ◽  
Megan Orr ◽  
Xianyao Li ◽  
Huaijun Zhou ◽  
timothy J. Johnson ◽  
...  

Author(s):  
Ranu Kumar ◽  
Prasad Kapildeo

We are traditionally used Microscope in clinical laboratory for determination of white blood cells of human blood smear. Now, in this study we were used Foldscope with Smartphone in the place of Microscope and examine many samples of human blood smear which was collected from local diagnostic centers. We were very easily quantity & morphology analysis of all types of WBC cells such as Neutrophils, Lymphocytes, Monocytes, Eosionophils, Basophils in blood smear with the help of Foldscope & image taken by Smartphone. The main objective of this study is to use Foldscope for quantity & morphology analysis of human WBCs at field level especially poor resource area where healthcare services or centers is not available & where carry of microscope is not possible.


Sign in / Sign up

Export Citation Format

Share Document