scholarly journals Olig1 and Olig2 promotes oligodendrocyte differentiation of neural stem cells in adult mice injured by EAE

2012 ◽  
Vol 03 (05) ◽  
pp. 567-573 ◽  
Author(s):  
Tamara L. Adams ◽  
Joseph M. Verdi
Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Rui Lan Zhang ◽  
Michael Chopp ◽  
Cynthia Roberts ◽  
Siamak Nejad-Davarani ◽  
Li Zhang ◽  
...  

Stroke induces angiogenesis in the peri-infarct region. It is not known whether angiogenesis occurs in the subventricular zone (SVZ) of the lateral ventricle after stroke. The SVZ is a neural stem cell niche containing vascular plexus that supports adult neurogenesis. We characterized longitudinal changes of vascular structures in the SVZ niche after stroke using whole mounts, an organotypic preparation of the SVZ in which the 3D cell-vessel relationships are preserved. Adult mice were subjected to middle cerebral artery occlusion (MCAO). The vascular architectures within the 50 μm thick SVZ of immunostained whole mounts were imaged by 3D confocal microscopy. In non-MCAO mice (n=4), 2±0.2% of endothelial cells were proliferative (BrdU+/CD31+). Blood vessels in this niche constituted 2.6±0.01% of the total volume with 75±17 vascular branches. However, 7 and 14 days after MCAO, proliferated endothelial cells significantly (p<0.05) increased to 12±1% (n=5) and 15±1 % (n=5), respectively, which was followed by substantial increases in vascular volume at 14 (4.2±0.01%, n=3), 30 (4.9±0.05%, n=3), and 90 (5.7±0.01%, n=3) days, but not at 7 days after MCAO. Moreover, vascular branches increased significantly to 156±27 and 216±8 at 30 and 90 days, respectively, but not at 14 days. Interestingly, we detected increases in the number of string-like vessels starting at 14 days (731±79/mm 3 vs 476±41/mm 3 in control) which increased and persisted at 30 (1,824±255/mm 3 ) and 90 (1,748±204/mm 3 ) days after MCAO. These string-like vessels were not perfused by plasma. String vessels increase during embryonic angiogenesis. Collectively, these data indicate that stroke induces angiogenesis in the SVZ, which lasts at least 90 days after stroke. Moreover, stroke significantly increased neural stem cells (BrdU + /GFAP + , 13±3%, 15±3%, and 11±4% at 7, 14, and 90 days, respectively, vs 6±1% in control) and newborn neurons (BrdU + /DCX + , 14±2% and 12±2.0% at 7 and 14 days, respectively, vs 4±1% in control). Neural stem cells at the ventricular surface extended their processes to the blood vessels in the SVZ. Our data indicate that stroke induces angiogenesis in the SVZ, which is associated with stroke-induced neurogenesis.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Auston Eckert ◽  
Milton H Hamblin ◽  
Jean-Pyo Lee

Background: Presently, tissue plasminogen activator (tPA) is the sole FDA-approved antithrombotic treatment available for stroke. However, tPA’s harmful side effects within the central nervous system can exacerbate blood-brain barrier (BBB) damage and increase mortality. Patients should receive tPA less than 4.5 hours post-stroke. Although age alone is not an impediment for tPA treatment, the harmful effects of delayed tPA (>4.5h), particularly on aged stroke animals, have not been well studied. We reported that intracranial transplantation of neural stem cells (hNSCs) ameliorates BBB damage caused by ischemic stroke. In this study, we examined the combined effects of minocycline (a neuroprotective and anti-inflammatory drug) and hNSC transplantation on the mortality of delayed tPA-treated aged mice within 48h post-stroke. Methods and Results: We utilized the middle cerebral artery occlusion stroke mouse model to induce focal cerebral ischemia followed by reperfusion (MCAO/R). 6h post-MCAO, we administered tPA intravenously. Minocycline was administered intraperitoneally at various time points prior to tPA injection. One day post-stroke, we injected hNSCs intracranially. Previously, we reported that hNSCs (both human and mouse) transplanted into the brain 24h post-stroke rapidly improve neurological outcome in young-adult mice (4-5mo). In our current study, tPA administered within 4.5h did not increase mortality in either young-adult or aged mice. However, we found delayed tPA treatment (6h post-stroke) significantly increased the mortality of aged mice (13-18 mo) but not in young-adult mice. Here, we report that by combining minocycline prior to tPA significantly reduced mortality. Furthermore, transplanting hNSCs in minocycline-treated mice further ameliorated the pathophysiology caused by delayed tPA. Conclusions: Our findings implicate that administering the anti-apototic and anti-inflammatory drug prior to tPA injection, and then post-treating with multipotent neuroprotective hNSCs might expand the time window of tPA and reduce reperfusion injury.


2019 ◽  
Vol 49 (1) ◽  
pp. e80
Author(s):  
Krutika Deshpande ◽  
Behnaz Saatian ◽  
Vahan Martirosian ◽  
Michelle Lin ◽  
Alex Julian ◽  
...  

2007 ◽  
Vol 426 (2) ◽  
pp. 69-74 ◽  
Author(s):  
Hiroki Takeuchi ◽  
Atsushi Natsume ◽  
Toshihiko Wakabayashi ◽  
Chihiro Aoshima ◽  
Shinji Shimato ◽  
...  

2005 ◽  
Vol 27 (8) ◽  
pp. 812-819 ◽  
Author(s):  
Hajime Kimura ◽  
Masahide Yoshikawa ◽  
Ryousuke Matsuda ◽  
Hayato Toriumi ◽  
Fumihiko Nishimura ◽  
...  

2016 ◽  
Vol 37 (7) ◽  
pp. 1319-1324 ◽  
Author(s):  
Majid Ghareghani ◽  
Heibatollah Sadeghi ◽  
Kazem Zibara ◽  
Nazanin Danaei ◽  
Hassan Azari ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A802-A802
Author(s):  
Neerupma Silswal ◽  
Joe Bean ◽  
Herschel Gupta ◽  
Fatma Talib ◽  
Suban Burale ◽  
...  

Abstract Twelve percent of pregnant women receive glucocorticoids (sGCs) to reduce the risks to reduce morbidity and mortality associated with preterm birth in infants. The two most commonly administered sGC are Dexamethasone (Dex) and Betamethasone (Beta) and they serve to decrease the severity of respiratory distress, intraventricular hemorrhage and necrotizing enterocolitis. However, repeated administration of sGC has been shown to be associated with adverse neurological outcome and depends on the type of sGCs used, dose, timing of sGCs administration and sex. We have previously shown that prenatal exposure to Dex in a murine model lead to sex specific changes in the transcription response and in the biological function of neural stem cells and to long-term changes in brain architecture and behavior. Beta is the predominant sGC used prenatally in the United States, therefore these studies investigated the cellular and molecular responses to beta exposure on the neural stem cells in-vitro and anatomical organization of the brain in-vivo. Murine NSCs were isolated from the E14.5 cerebral cortex and exposed to 10-7 M Dex, 10-7 M Beta, or Vehicle for 4 or 24 hours and the immediate and long-term impact on transcription, proliferation and neuronal, glial and oligodendrocyte differentiation examined. Affymetrix genome transcriptional analyses reveal sex specific responses to Dex vs Beta in 4 hours. In females 682 genes were differentially regulated by Dex compared to 576 by Beta. In contrast, 875 were altered by Dex and 576 by Beta in males (Fold change &gt; +/- 1.5, P&lt; 0.05). Select target genes were independently validated by QPCR. Ingenuity Pathway Analysis was used to identify unique and overlapping pathways that were altered by Dex vs Beta. In males, Dex uniquely altered 34 pathways including, Thyroid Hormone Metabolism, ERK5 Signaling and Opioid Signaling while Bata altered 33 pathways including, Phagasome formation, IL-7 Signaling and JAK STAT signaling. In Females, Dex altered 45 pathways including Calcium Signaling, Serotonin Receptor Signaling and Xenobiotic Signaling, while Beta altered 46 pathways including, FXR/RXR Activation, Tec Kinase Signaling and D-myo-Inositol-5-Phosphate Metabolism. Another 35 pathways were altered by both Dex and Beta but they showed differences in genes activated or repressed. Dex and Beta, both significantly altered genes involved in proliferation and differentiation therefore the biological response of NSC to sGCs stimulation in vitro and the long term consequences of sGC exposure in-vivo was compared. Distinct differences in cell proliferation, glial and oligodendrocyte differentiation were observed. These results reveal gene targets, cellular pathways and processes that are differentially altered by prenatal Dex vs Beta exposure. Our finds may provide insights into the sex specific neurological outcomes observed in children exposed to sGCs in-utero.


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