Effects of retinoic acid on ischemic brain injury-induced neurogenesis

Jung, Dae-Soo; Baek, Sun‐Yong; Park, Kyu Hyun; Chung, Yeong Jin; Kim, Hak-Jin; Kim, Chi-Dae; Cho, Minkyoung; Han, Myoung‐Eun; Park, Kyung-Pil; Kim, Bong-Seon; Kim, Jae-Bong; Oh, Sae‐Ock

doi:10.1038/emm.2007.34

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…Our data suggest that RA further increases SVZ neurogenesis in the chronic stages after stroke. Contrary to our findings, a recent study found that RA-treatment after photothrombotic stroke decreased BrdU and DCx in the SVZ (Jung, et al, 2007). This study assessed only acute (7 days after injury) proliferation effects, which may be one reason for the disparities with our findings.…”

Section: Discussioncontrasting

confidence: 99%

Retinoic acid and environmental enrichment alter subventricular zone and striatal neurogenesis after stroke

Plane

Whitney

Schallert

et al. 2008

Experimental Neurology

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Neurogenesis increases in the adult rodent forebrain subventricular zone (SVZ) after experimental stroke. Newborn neurons migrate to the injured striatum, but few survive long-term and little evidence exists to suggest that they integrate or contribute to functional recovery. One potential strategy to improve stroke recovery is to stimulate neurogenesis and integration of adult-born neurons by using treatments that enhance neurogenesis. We examined the influence of retinoic acid (RA), which stimulates neonatal SVZ and adult hippocampal neurogenesis, and environmental enrichment (EE), which enhances survival of adult-born hippocampal neurons. We hypothesized that the combination of RA and EE would promote survival of adult-generated SVZ-derived neurons and improve functional recovery after stroke. Adult rats underwent middle cerebral artery occlusion, received BrdU on days 5-11 after stroke and were treated with RA/EE, RA alone, EE/vehicle or vehicle alone and were killed 61 days after stroke. Rats underwent repeated MRI and behavioral testing. We found that RA/EE treatment preserved striatal and hemisphere tissue and increased SVZ neurogenesis as demonstrated by Ki67 and doublecortin (DCx) immunolabeling. All treatments influenced the location of BrdU-and DCx-positive cells in the post-stroke striatum. RA/EE increased the number of BrdU/NeuN-positive cells in the injured striatum but did not lead to improvements in behavioral function. These results demonstrate that combined pharmacotherapy and behavioral manipulation enhances post-stroke striatal neurogenesis and decreases infarct volume without promoting detectable functional recovery. Further study of the integration of adult-born neurons in the ischemic striatum is necessary to determine their restorative potential.

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Section: Discussioncontrasting

confidence: 99%

Retinoic acid and environmental enrichment alter subventricular zone and striatal neurogenesis after stroke

Plane

Whitney

Schallert

et al. 2008

Experimental Neurology

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“…Our previous findings (Crandall et al,2004; Sakai et al,2004) as well as those of others (Jung et al,2007), found that exposure to RA can inhibit cell proliferation (and neurogenesis) in the SGZ or the SVZ. It is possible that these differences may, in part, reflect the precursor type examined; Jacobs et al studied precursors labeled following exposure to BrdU over a 6-day period as opposed to the much briefer 6 hr exposure to BrdU used in this study.…”

Section: Discussionsupporting

confidence: 66%

Patterning of retinoic acid signaling and cell proliferation in the hippocampus

et al. 2012

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The nuclear receptor ligand retinoic acid (RA) has been identified as an endogenous regulatory factor in the hippocampus, acting on pyramidal neurons and granule neuron progenitors, but almost nothing is known about the distribution of RA itself in the hippocampus. This study describes the source of RA for the rodent hippocampus in the meninges via the key RA synthetic enzyme retinaldehyde dehydrogenase 2 (RALDH2). Diffusion of RA from the meninges potentially creates a gradient of RA across the infrapyramidal and suprapyramidal blades of the dentate gyrus, enhanced by the expression of the RA catabolic enzyme Cyp26B1 between the blades, and an infrapyramidal and suprapyramidal blade difference is evident in RA-regulated transcription. This asymmetry may contribute to some of the physiological and molecular differences between the blades, including a disparity in the rates of cell proliferation in the subgranular zone of the two blades through RA inhibition of cell proliferation. Such differences can be altered by either the application of excess RA, its effect dependent on the relative position along the septotemporal axis, or change in RA signaling through mutation of retinol binding protein, while the capacity of RA to inhibit proliferation of cells in the dentate gyrus is demonstrated using in vitro slice culture. Use of synthetic and catabolic enzymes in the hippocampus to create differing zones of RA concentration parallels the mechanisms used in the developing brain to generate patterns of RA-regulated transcription. © 2012 Wiley Periodicals, Inc.

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“…The brains were removed, immersed in 30% sucrose in 0.1 M phosphate buffer at 4 o C, and then frozen and sectioned coronally at 30 µm on a cryostat through the striatum. A series of consecutive sections/brain were prepared for further processing (Jung et al, 2007). Beta-galactosidase was detected by incubating brain sections for 3 h at 37 o C in reaction solution consisting of PBS containing 4 mM potassium ferricyanide (Sigma, St. Louis, MO), 4 mM potassium ferrocyanide (Sigma), 4 mM magnesium chloride (Sigma), and 0.4 mg/ml 5-bromo-4-chloro-3-indolyl β-D-galactoside (X-gal, Sigma).…”

Section: Tissue Processing Immunohistochemistry and X-gal Stainingmentioning

confidence: 99%

Migration of human neural stem cells toward an intracranial glioma

Jeon

Kim

et al. 2008

Exp Mol Med

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Many in vivo and in vitro studies have demonstrated the targeted migration of neural stem cells (NSC) to infiltrating brain tumors, including malignant glioma, highlighting a potential therapeutic approach. However, there is not enough information to apply this approach to clinical therapy. The most important things in stem cell therapy for brain tumors involve selecting the appropriate neural progenitor type and optimizing the efficiency of the cell engraftment. By histological analysis using two different live-dyes, human NSCs were shown to migrate away from the transplanted site in the direction of the expanding C6 glioma and to intermix with the tumor bed, especially with the tumor core. This intermixing occurred within 7 days when NSCs were implanted into glioma model. The time course of migratory HB1.F5 with the greatest mobility of three NSC lines was as follows. As early as 3 days after transplantation, several NSCs were found leaving the implant site, primarily approaching microsatellites and frontier cells located near the site of NSC implantation. Through 7 days post-transplantation, massive numbers of NSCs continued to be attracted to and interspersed with C6 glioma, and were finally distributed extensively throughout the whole tumor bed, including the core and penumbra of the tumor mass. However, NSCs appeared to penetrate into the tumor mass very well, whereas normal fibroblast cells could not migrate. These findings strengthen the potential for human NSCs as attractive vehicles to improve therapeutic gene delivery to cancer or glioma if they are optimized to selectively kill neoplastic cells.

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Effects of retinoic acid on ischemic brain injury-induced neurogenesis

Cited by 9 publications

References 45 publications

Retinoic acid and environmental enrichment alter subventricular zone and striatal neurogenesis after stroke

Retinoic acid and environmental enrichment alter subventricular zone and striatal neurogenesis after stroke

Patterning of retinoic acid signaling and cell proliferation in the hippocampus

Migration of human neural stem cells toward an intracranial glioma

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