scholarly journals The Effects of Vascular Cognitive Impairment on the Thickness of the Granular Cell Layer of the Dentate Gyrus within the Hippocampus in a Mouse Model

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Akshaya Radhakrishnan ◽  
Nafisa Jadavji
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
Folic Acid ◽  
Mouse Model ◽  
Dentate Gyrus ◽  
Cell Layer ◽  
Control Diet ◽  
Granular Cell ◽  
Vascular Cognitive Impairment ◽  
Granular Cell Layer

     Vascular Cognitive Impairment (VCI) is a form of dementia, most prevalent after Alzheimer’s Disease. However, VCI remains the second leading cause for dementia because it restricts blood flow to the brain and there are currently no treatments. There has been a positive correlation between VCI and hippocampal atrophy reported. Diet such as deficiencies in folic acid, is a modifiable risk factor for neurodegeneration. In the present study, a mouse model of VCI was combined with a deficiency in folic acid to assess hippocampal morphology. Animals were split into 4 experimental groups where they were placed into a control diet (CD) or folic acid deficient diet (FADD), and later these animals either had microcoils implanted around their common carotid arteries to model VCI or a sham, control surgery.  For hippocampal morphological analysis, the thickness of the granular cell layer of the dentate gyrus within the hippocampus was measured. It was hypothesized that a mouse model of VCI with microcoil treatment and reduced levels of folic acid would reduce blood flow, and increase cell death resulting in a reduced thickness of the granular cell layer within the dentate gyrus of the hippocampus. Our results show that thickness had an increasing trend in the in the FADD microcoil group. These data suggest that there may be an additional factor coming into play such as compensation by neural stem cells that needs to be further researched.

Immunohistochemical Analysis of GDNF and Its Cognate Receptor GFRα-1 Protein Expression in Vitiliginous Skin Lesions

2015 ◽  
Vol 20 (2) ◽  
pp. 130-134 ◽  
Author(s):  
Mohamed A. Adly ◽  
Hanan A. Assaf ◽  
Shaima’a F. Abdel-Rady ◽  
Nagwa Sayed Ahmed ◽  
Mahmoud Rezk Abdelwahed Hussein
Keyword(s):  
Protein Expression ◽  
Basal Cell ◽  
Cell Layer ◽  
Expression Patterns ◽  
Granular Cell ◽  
Epidermal Keratinocytes ◽  
Healthy Skin ◽  
Granular Cell Layer ◽  
Cognate Receptor ◽  
Spinous Layer

Background: Vitiligo is an idiopathic skin disease, characterized by circumscribed white macules or patches on the skin due to loss of the functional melanocytes. Glial cell line–derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are distal members of the transforming growth factor-β superfamily. GDNF, produced by the basal cell keratinocytes, is involved in the migration and differentiation of the melanocytes from the neural crest to the epidermis. This study examines the hypothesis that expression of GDNF protein and its cognate receptor GFRα-1 protein is altered in vitiliginous skin. Patients and Methods: To test our hypothesis, we examined the expression patterns of these proteins in vitiliginous and corresponding healthy (control) skin biopsies (20 specimens each) using immunoperoxidase staining techniques. Results: We found variations between the vitiliginous skin and healthy skin. In healthy skin, the expression of GDNF and GFRα-1 proteins was strong (basal cell keratinocytes and melanocytes), moderate (spinous layer), and weak (granular cell layer). In contrast, weak expression of GDNF protein was observed in all epidermal layers of vitiliginous skin. GFRα-1 protein expression was strong (basal cell keratinocytes and melanocytes), moderate (spinous layer), and weak (granular cell layer). In both healthy skin and vitiliginous skin, the expression of GDNF and GFRα-1 proteins was strong in the adnexal structures. Conclusions: We report, for the first time, decreased expression of GDNF proteins in the epidermal keratinocytes of vitiliginous skin. Our findings suggest possible pathogenetic roles for these proteins in the development of vitiligo. The clinical ramifications of these observations mandate further investigations.

scholarly journals Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e040466
Author(s):  
Aravind Ganesh ◽  
Philip Barber ◽  
Sandra E Black ◽  
Dale Corbett ◽  
Thalia S Field ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Vascular Cognitive Impairment ◽  
White Matter Injury ◽  
White Matter Hyperintensity ◽  
Limb Ischaemia ◽  
Ischaemic Brain

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

Transcriptome differentiation along the dorso–ventral axis in laser-captured microdissected rat hippocampal granular cell layer

Neuroscience ◽  
2010 ◽  
Vol 170 (3) ◽  
pp. 731-741 ◽  
Author(s):  
T. Christensen ◽  
C.F. Bisgaard ◽  
H.B. Nielsen ◽  
O. Wiborg
Keyword(s):  
Cell Layer ◽  
Granular Cell ◽  
Granular Cell Layer

P3714Cerebral blood flow and cognitive functioning in the heart-brain axis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A E Leeuwis ◽  
A M Hooghiemstra ◽  
E E Bron ◽  
H P Brunner-La Rocca ◽  
L J Kappelle ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
Cognitive Functioning ◽  
Sex Education ◽  
Vascular Cognitive Impairment ◽  
Cognitive Domain ◽  
Cardiovascular Research ◽  
Whole Brain ◽  
Symptomatic Carotid ◽  
Brain Study

Abstract Background Recent studies suggest that cardiovascular disease and dementia are closely related, which led to the concept of a “heart-brain axis”. Dysfunction in any component of the heart-brain axis could be a risk factor for the development of brain damage and consequently to the development of cognitive impairment. In the Heart-Brain study, we focus on vascular cognitive impairment (VCI), symptomatic carotid occlusive disease (COD) and heart failure (HF) as three extreme phenotypes of haemodynamic dysfunction in different components of the heart-brain axis (i.e. heart – carotids – brain). We compared values of cerebral blood flow (CBF), measured with arterial spin labeling (ASL) between patients with HF, COD and VCI and investigated the association between CBF and cognitive functioning. Methods We included 442 participants (129 VCI; 75 COD; 124 HF; and 114 controls) from the Heart-Brain Study (67±9 yrs; 38% F; MMSE 28±2). We used 3T pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Using a standardized neuropsychological assessment, we measured global cognitive functioning and four cognitive domains. Compound z-scores were constructed for each cognitive domain. We investigated associations using linear regression analyses, adjusted for age, sex, education, center and diagnosis. Subsequently, we stratified for diagnosis. Results Whole-brain and regional CBF values were lowest in patients with COD, followed by VCI and HF, compared to controls. Global cognitive functioning was lowest in patients with VCI, followed by COD and HF, compared to controls. Overall, we found hardly any association between whole-brain or regional CBF values and cognitive functioning (standardized beta [stb] = 0.00–0.10, p>0.05). Subsequent stratification for diagnosis showed no association between whole-brain or regional CBF and cognitive functioning in any participant group. Conclusions Our results suggest that reduced CBF is not the major explanatory factor underlying impaired cognitive functioning in patients with disorders along the heart-brain axis. The predisposition of cognitive impairment in these patients is likely to be driven by other (haemodynamic) mechanisms than CBF. Acknowledgement/Funding We acknowledge the support of the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection), Du

scholarly journals Uncoupling of Microvascular Blood Flow and Capillary Density in Vascular Cognitive Impairment

2019 ◽  
Vol 10 ◽  
Author(s):  
Chenxing Eleana Zhang ◽  
Julie Staals ◽  
Robert Jan van Oostenbrugge ◽  
Hans Vink
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
Vascular Cognitive Impairment ◽  
Capillary Density ◽  
Microvascular Blood Flow

scholarly journals Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment

2015 ◽  
Vol 6 (5) ◽  
pp. 390-398 ◽  
Author(s):  
Kristen L. Zuloaga ◽  
Wenri Zhang ◽  
Lauren A. Yeiser ◽  
Blair Stewart ◽  
Ayaka Kukino ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model ◽  
Vascular Cognitive Impairment ◽  
Hippocampal Atrophy

External granular cell layer bobbling: a distinct histomorphological feature of the developing human cerebellum

2013 ◽  
Vol 32 (01) ◽  
pp. 42-50 ◽  
Author(s):  
Ellen Gelpi ◽  
Herbert Budka ◽  
Matthias Preusser
Keyword(s):  
Cell Layer ◽  
Granular Cell ◽  
Granular Cell Layer ◽  
Human Cerebellum
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