Evolutional Characterization of Photochemically Induced Stroke in Rats: a Multimodality Imaging and Molecular Biological Study

Liu, Nai Wei; Ke, Chien-Chih; Zhao, Yonghua; Chen, Yi An; Chan, Kang Cheung; Tan, David; Lee, Jhih Shian; Hsu, Tun-Wei; Hsieh, Yu‐Hsuan; Chang, Chi Wei; Yang, Bohan; Huang, Wen Sheng; Liu, Ru‐Shi

doi:10.1007/s12975-016-0512-4

Cited by 44 publications

(53 citation statements)

References 46 publications

(48 reference statements)

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“…Our pervious study indicated that the leakage of BBB gradually increased at day 3 and began to restore at day 7 in rat PTS model . In this study, we sought to evaluate the restoration of BBB disruption after treatment.…”

Section: Resultsmentioning

confidence: 99%

“…The details of experimental method were described in our previous study . Briefly, 7‐week old male Sprague‐Dawley (SD) rats under anesthetization was illuminated by a laser beam with 532 nm wavelength at the middle of the craniotomic window which was made over the somatosensory cortex with the center at the coordinate of 1 mm rostrally from the bregma and 3.5 mm lateral to the midline for 30 minutes upon slow injection of rose bengal (20 mg/kg body weight) through tail vein.…”

Section: Methodsmentioning

confidence: 99%

“…Perfusion‐weighted imaging (PWI) was performed with the procedure described in our previous report . BioSpec‐70/30 7T system (Bruker, Ettlingen, Germany) with a birdcage head‐coil of 75 mm inner diameter for radio frequency (RF) transmission and a 20 mm diameter surface coil for reception were used.…”

Section: Methodsmentioning

confidence: 99%

“…The glucose metabolism measured by 18 F‐2‐deoxy‐glucose (FDG)‐PET/CT imaging was performed according to the protocol described in our previous report . Before imaging, SD rats in each group (n = 6) were fasted for 12 hours.…”

Section: Methodsmentioning

confidence: 99%

“…Disruption of blood‐brain barrier (BBB) after photothrombotic stroke was evaluated by in vivo Evans blue (EB) fluorescent imaging . Briefly, 2 hours after EB dye (Sigma, 10 mg/mL in saline, 2.5 mL/kg rat weight) was injected via tail vein, animals in each group (n = 6) at day 3 and 7 were killled with an overdose of pentobarbital injection (RMB, Animal Health Ltd., UK).…”

Section: Methodsmentioning

confidence: 99%

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Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke

Zhao

Liu

et al. 2018

J Cellular Molecular Medi

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The remodelling of structural and functional neurovascular unit (NVU) becomes a central therapeutic strategy after cerebral ischaemic stroke. In the present study, we investigated the effect of combined therapy of sodium ferulate (SF), n‐butylidenephthalide (BP) and adipose‐derived stromal cells (ADSCs) to ameliorate the injured NVU in the photochemically induced thrombotic stroke in rats. After solely or combined treatment, the neovascularization, activation of astrocytes, neurogenesis, expressions of vascular endothelial growth factor (VEGF) and claudin‐5 were assessed by immunohistochemical or immunofluorescence staining. In order to uncover the underlying mechanism of therapeutic effect, signalling of protein kinase B/mammalian target of rapamycin (AKT/mTOR), extracellular signal‐regulated kinase 1/2 (ERK1/2), and Notch1 in infarct zone were analysed by western blot. 18F‐2‐deoxy‐glucose/positron emission tomography, magnetic resonance imaging, Evans blue staining were employed to evaluate the glucose metabolism, cerebral blood flow (CBF), and brain‐blood barrier (BBB) permeability, respectively. The results showed that combined treatment increased the neovascularization, neurogenesis, and VEGF secretion, modulated the astrocyte activation, enhanced the regional CBF, and glucose metabolism, as well as reduced BBB permeability and promoted claudin‐5 expression, indicating the restoration of structure and function of NVU. The activation of ERK1/2 and Notch1 pathways and inhibition of AKT/mTOR pathway might be involved in the therapeutic mechanism. In summary, we have demonstrated that combined ADSCs with SF and BP, targeting the NVU remodelling, is a potential treatment for ischaemic stroke. These results may provide valuable information for developing future combined cellular and pharmacological therapeutic strategy for ischaemic stroke.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke

Zhao

Liu

et al. 2018

J Cellular Molecular Medi

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Vascular perfusion differs in two distinct PDGFRβ‐positive zones within the ischemic core of male mice 2 weeks following photothrombotic stroke

Morris

Gowing

Courtney

et al. 2022

J of Neuroscience Research

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Stroke therapy has largely focused on preventing damage and encouraging repair outside the ischemic core, as the core is considered irreparable. Recently, several studies have suggested endogenous responses within the core are important for limiting the spread of damage and enhancing recovery, but the role of blood flow and capillary pericytes in this process is unknown. Using the Rose Bengal photothrombotic model of stroke, we illustrate blood vessels are present in the ischemic core and peri‐lesional regions 2 weeks post stroke in male mice. A FITC‐albumin gel cast of the vasculature revealed perfusion of these vessels, suggesting cerebral blood flow (CBF) may be partially present, without vascular leakage. The length of these vessels is significantly reduced compared to uninjured regions, but the average width is greater, suggesting they are either larger vessels that survived the initial injury, smaller vessels that have expanded in size (i.e., arteriogenesis), or that neovascularization begins with larger vessels. Concurrently, we observed an increase in platelet‐derived growth factor receptor beta (PDGFRβ, a marker of pericytes) expression within the ischemic core in two distinct patterns, one which resembles pericyte‐derived fibrotic scarring at the edge of the core, and one which is vessel associated and may represent blood vessel recovery. We find little evidence for dividing cells on these intralesional blood vessels 2 weeks post stroke. Our study provides evidence flow is present in PDGFRβ‐positive vessels in the ischemic core 2 weeks post stroke. We hypothesize intralesional CBF is important for limiting injury and for encouraging endogenous repair following cerebral ischemia.

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Photothrombotic Stroke Model

Verma

Singhal

Anand

2021

Models and Techniques in Stroke Biology

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Evolutional Characterization of Photochemically Induced Stroke in Rats: a Multimodality Imaging and Molecular Biological Study

Cited by 44 publications

References 46 publications

Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke

Combined treatment of sodium ferulate, n‐butylidenephthalide, and ADSCs rehabilitates neurovascular unit in rats after photothrombotic stroke

Vascular perfusion differs in two distinct PDGFRβ‐positive zones within the ischemic core of male mice 2 weeks following photothrombotic stroke

Photothrombotic Stroke Model

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