scholarly journals Neurogenesis and Proliferation of Neural Stem/Progenitor Cells Conferred by Artesunate via FOXO3a/p27Kip1 Axis in Mouse Stroke Model

2021 ◽  
Author(s):  
Kaiyuan Zhang ◽  
Yang Yang ◽  
Hongfei Ge ◽  
Ju Wang ◽  
Xuejiao Lei ◽  
...  
Keyword(s):  
White Matter ◽  
Progenitor Cells ◽  
Functional Recovery ◽  
Diffusion Tensor ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
White Matter Injury ◽  
Electron Microscopic ◽  
Neuronal Precursor Cells ◽  
Neural Stem Progenitor Cells

Abstract Promoting neurogenesis and proliferation of endogenous neural stem/progenitor cells (NSPCs) is considered a promising strategy for neurorehabilitation after stroke. Our previous study revealed that a moderate dose of artesunate (ART, 150mg/kg) could enhance functional recovery in middle cerebral artery occlusion (MCAO) mice. This study aimed to investigate the effects of ART treatment on neurogenesis and proliferation of NSPCs using a rodent MCAO model. MRI results indicated that the ischemic brain volume of MCAO mice was reduced by ART treatment. The results of diffusion tensor imaging, electron microscopic, and immunofluorescence of Tuj-1 also revealed that ischemia-induced white matter lesion was alleviated by ART treatment. After ischemia/reperfusion, endogenous NSPCs were activated by ART, which was displayed by comparing the proportion of Brdu+ neuronal precursor cells in the ipsilateral subventricular zone and peri-infarct cortex. Furthermore, the neuro-restorative effects of ART were abolished by the overexpression of FOXO3a. These findings suggested that ART could rescue penumbra damage and alleviate white matter injury, subsequently contributing to post-stroke functional recovery by promoting neurogenesis and proliferation of endogenous NSPCs via the FOXO3a/p27Kip1 pathway.

Arterial Stiffness Is Associated with White Matter Disruption and Cognitive Impairment: A Community-Based Cohort Study

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Arterial Stiffness ◽  
Cognitive Decline ◽  
Sex Education ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Injury ◽  
White Matter Integrity ◽  
Cross Sectional

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

Transplantation of Neural Stem/Progenitor Cells at Different Locations in Mice with Spinal Cord Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1451-1464 ◽  
Author(s):  
Hiroki Iwai ◽  
Satoshi Nori ◽  
Soraya Nishimura ◽  
Akimasa Yasuda ◽  
Morito Takano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Functional Recovery ◽  
Control Group ◽  
Cord Injury ◽  
Neural Stem Progenitor Cells ◽  
Neurotropic Factor ◽  
Transplantation Site

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

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.

scholarly journals Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil

2011 ◽  
Vol 4 (1) ◽  
pp. 35 ◽  
Author(s):  
Junichi Yamane ◽  
Satoru Ishibashi ◽  
Masanori Sakaguchi ◽  
Toshihiko Kuroiwa ◽  
Yonehiro Kanemura ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Brain Ischemia ◽  
Functional Recovery ◽  
Mongolian Gerbil ◽  
Neural Stem Progenitor Cells ◽  
Focal Brain Ischemia

Exploring mania-associated white matter injury by comparison with multiple sclerosis: a diffusion tensor imaging study

2018 ◽  
Vol 281 ◽  
pp. 78-84 ◽  
Author(s):  
Niccolò Piaggio ◽  
Simona Schiavi ◽  
Matteo Martino ◽  
Giulia Bommarito ◽  
Matilde Inglese ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
White Matter Injury ◽  
Diffusion Tensor Imaging Study

scholarly journals Correlation Between White Matter Injury Identified by Neonatal Diffusion Tensor Imaging and Neurodevelopmental Outcomes Following Term Neonatal Asphyxia and Therapeutic Hypothermia: An Exploratory Pilot Study

2019 ◽  
Vol 34 (10) ◽  
pp. 556-566 ◽  
Author(s):  
Gwendolyn J. Gerner ◽  
Eric I. Newman ◽  
V. Joanna Burton ◽  
Brenton Roman ◽  
Elizabeth A. Cristofalo ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Pilot Study ◽  
Therapeutic Hypothermia ◽  
Diffusion Tensor ◽  
White Matter Injury ◽  
Hypoxic Ischemic Encephalopathy ◽  
Group Differences ◽  
Neurodevelopmental Outcomes ◽  
Ischemic Encephalopathy

Aim: Hypoxic-ischemic encephalopathy is associated with damage to deep gray matter; however, white matter involvement has become recognized. This study explored differences between patients and clinical controls on diffusion tensor imaging, and relationships between diffusion tensor imaging and neurodevelopmental outcomes. Method: Diffusion tensor imaging was obtained for 31 neonates after hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and 10 clinical controls. A subgroup of patients with hypoxic-ischemic encephalopathy (n = 14) had neurodevelopmental outcomes correlated with diffusion tensor imaging scalars. Results: Group differences in diffusion tensor imaging scalars were observed in the putamen, anterior and posterior centrum semiovale, and the splenium of the corpus callosum. Differences in these regions of interest were correlated with neurodevelopmental outcomes between ages 20 and 32 months. Conclusion: Therapeutic hypothermia may not be a complete intervention for hypoxic-ischemic encephalopathy, as neonatal white matter changes may continue to be evident, but further research is warranted. Patterns of white matter change on neonatal diffusion tensor imaging correlated with neurodevelopmental outcomes in this exploratory pilot study.

scholarly journals Diffusion Tensor Imaging of White Matter Injury Caused by Prematurity-Induced Hypoxic-Ischemic Brain Damage

2016 ◽  
Vol 22 ◽  
pp. 2167-2174 ◽  
Author(s):  
Fuyong Zhang ◽  
Chunli Liu ◽  
Linlin Qian ◽  
Haifeng Hou ◽  
Zhengyi Guo
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Brain Damage ◽  
Diffusion Tensor ◽  
White Matter Injury ◽  
Ischemic Brain Damage ◽  
Ischemic Brain

scholarly journals Thalamic and thalamic projection abnormalities on DTI and NODDI analysis following acute concussion

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S4.2-S5
Author(s):  
James Houston ◽  
Frank Skidmore ◽  
William Monroe ◽  
Jon Amburgy ◽  
Mitchell Self
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Oculomotor System ◽  
White Matter Injury ◽  
Football Players ◽  
Cortical Regions ◽  
The Right ◽  
Collegiate Football ◽  
Concussive Injury

ObjectiveTo compare preseason and post-concussive MRI in a cohort of collegiate football players utilizing Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) post processing.BackgroundAcute post-concussive symptoms can vary in clinical characteristics and severity. However, vestibular and ocular dysfunction in particular, has been associated with poor clinical outcomes. The vestibular system comprises a complex network of projections from peripheral vestibular organs to thalamic relay systems and numerous cortical regions. The visual/oculomotor system is also complex, involving brainstem, subcortical-cortical and thalamo-cortical connections. Oculomotor deficits are thought to involve the midbrain and the visual and parietal association cortices, both of which have thalamic projections.Design/MethodsWe gathered pre-season MR diffusion weighted imaging on a cohort of 30 collegiate football players. We performed repeat imaging within 36 hours of any diagnosed concussion in the same subject cohort. DTI metrics: mean diffusivity (MD), axial diffusivity (AD), fractional anisotropy (FA), and radial diffusivity (RD) along with NODDI metric: orientation dispersion index (ODI), were analyzed for statistical comparisons between groups.Results4 subjects with pre-season MRI underwent repeat MRI within 36 hours of concussive injury. A paired t-test between these two groups using DTI and NODDI metrics showed significant (p < 0.05) decreases in: AD and MD in the left posterior thalamic radiations, FA in the column and body of the fornix, and MD in the right anterior corona radiata and superior fronto-occipital fasciculus, and a significant decrease in ODI in the anterior thalamus.ConclusionsDisruptions in the thalamus and its white matter projections may play a role in the vestibular/ocular dysfunction associated with acute concussive injury. While our numbers are small, the findings suggest that DTI and NODDI processing techniques have the capability to locate and measure grey and white matter injury patterns after concussive injury.

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