3D Image Analysis of the Complete Ventricular-Subventricular Zone Stem Cell Niche Reveals Significant Vasculature Changes and Progenitor Deficits in Males Versus Females with Aging

Zhao, Xueping; Wang, Yue; Wait, Eric; Mankowski, Walter; Bjornsson, Chris S.; Cohen, Andrew R.; Zuloaga, Kristen L.; Temple, Sally

doi:10.1016/j.stemcr.2021.03.012

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…Apparently, the addition of Clo predominately contributed to the constriction of the blood vessel. Afterwards, blood flow velocity was locally monitored over time, which was proved to be inversely proportional to the local vascular diameter according to Bernoulli's principle 34 . It was obvious that the blood flow velocity significantly increased by 157.1% (28.17/17.93 cm/s) at 4 h post-injection of Fiber-Rop/Gel-Clo and slightly attenuated at 8 h ( Figure 3 D and 3 E ), compared to the velocity before administration.…”

Section: Resultsmentioning

confidence: 99%

Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia

Chen¹,

Yao²,

Wang³

et al. 2022

Theranostics

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Rationale : Peripheral nerve block is a traditional perioperative analgesic method for its precise pain control and low systemic toxicity. However, a single low dose of local anesthetic merely provides a few hours of analgesia, and high dose results in irreversible toxicity, whereas continuous infusion of anesthetics is expensive and complicated. Therefore, it is necessary to develop a long-acting and sensory-selective local anesthetic for safe perioperative analgesia. Methods : An injectable composite comprising ropivacaine-loaded poly (ε-caprolactone) electrospun fiber and clonidine-loaded F127 hydrogel (Fiber-Rop/Gel-Clo composite) was developed for long-acting and walking regional analgesia with barely one dose. The peripheral nerve blockade effect of the composite was evaluated in a rat sciatic nerve block model. Also, the biodegradability and biosafety of the composite was evaluated. Results : The preferentially released Clo from the hydrogel rapidly constricted the peripheral arterial vessels, reducing the blood absorption of Rop and thus enhancing the local Rop accumulation at the injection site. The subsequently sustainable release of Rop from the fiber, significantly prolonged the sciatic nerve block of rats. Remarkably, an amazing sensorimotor segregation effect was achieved, as the sensory blockade (32.0 ± 1.4 h) lasted significantly longer than the motor blockade (20.3 ± 0.9 h). Additionally, the Fiber-Rop/Gel-Clo composite presented good biodegradability and biosafety in vivo . Conclusions : Our designed Fiber-Rop/Gel-Clo composite with minimal invasion, prolonged synergistic analgesia, and strikingly sensorimotor segregation effect, posted a promising prospect for regional long-term walking analgesia in clinical treatment.

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Section: Resultsmentioning

confidence: 99%

Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia

Chen¹,

Yao²,

Wang³

et al. 2022

Theranostics

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“…Analysis of the average distance between clusters and vessels displayed a significant increase with age ( Figure 5 E). However, with age DCX + clusters are less compact (see Figure S1 ) as well as undergoing vasculature structure changes (i.e., diameter, density, and tortuosity) ( Zhao et al., 2021 ), suggesting that the change in distance of clusters and blood vessels is in part due to fewer existing clusters near vessels to facilitate vasophilic migration. We found that a majority of the DCX + neuroblast clusters are within 0–20 μm distance of a blood vessel ( Figure 5 F).…”

Section: Resultsmentioning

confidence: 99%

Neuroblast migration along cellular substrates in the developing porcine brain

Porter

Henry²,

Ahmed³

et al. 2022

Stem Cell Reports

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“…The copyright holder for this preprint this version posted January 20, 2023. ; https://doi.org/10.1101/2023.01.18.524632 doi: bioRxiv preprint subventricular zone (V-SVZ), one of the locations in which neural stem cells (NSCs) reside (21,22). Neurogenesis was found to be more prominent in female mice compared to age-matched males with higher proliferating rates and lower numbers of apoptotic cells seen in the V-SVZ of adult mice (22).…”

Section: Discussionmentioning

confidence: 99%

Effects of Dopamine Receptor Antagonists and Radiation on Mouse Neural Stem/Progenitor Cells

Bhat

Ioannidis

et al. 2023

Preprint

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Background: Dopamine receptor antagonists are psychotropic drugs that have been originally developed against psychiatric disorders. We recently identified dopamine receptor antagonists as potential anti-cancer agents and some have entered clinical trials against glioblastoma. Radiotherapy is known to cause cognitive impairment in patients receiving cranial irradiation through the elimination of neural stem/progenitor cells and subsequent loss of neurogenesis. Methods: Using transgenic mice that report the presence of neural stem/progenitor cells through Nestin promoter-driven expression of enhanced green fluorescent protein, the effects of dopamine receptor antagonists alone or in combination with radiation on murine neural stem/progenitor cells were assessed in sphere-formation assays, flow cytometry and immunofluorescence in vitro and in vivo. Results: We report that several dopamine receptor antagonists show sex-dependent effects on neural stem/progenitor cells both in vitro and in vivo. Hydroxyzine, trifluoperazine, amisulpride, nemonapride or quetiapine alone or in combination with radiation significantly increased the number of neural stem/progenitor cells in female neurospheres but not in male mice. Dopamine receptor antagonists either protected neural stem/progenitor cells from radiation or expanded the stem cell pool, thus indicating that this combination therapy against glioblastoma will not increase radiation-induced cognitive decline through increasing elimination of neural stem/progenitor cells and subsequent loss of neurogenesis. Conclusions: We conclude that a therapeutic window for dopamine receptor antagonists in combination with radiation potentially exist, making it a novel combination therapy against glioblastoma. Normal tissue toxicity of this combination potentially differs depending on age and sex and should be taken into consideration when designing clinical trials.

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3D Image Analysis of the Complete Ventricular-Subventricular Zone Stem Cell Niche Reveals Significant Vasculature Changes and Progenitor Deficits in Males Versus Females with Aging

Cited by 7 publications

References 48 publications

Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia

Injectable electrospun fiber-hydrogel composite sequentially releasing clonidine and ropivacaine for prolonged and walking regional analgesia

Neuroblast migration along cellular substrates in the developing porcine brain

Effects of Dopamine Receptor Antagonists and Radiation on Mouse Neural Stem/Progenitor Cells

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