Blood barriers serve as key points of transport for essential molecules as well as lines of defense to protect against toxins. In vitro modeling of these barriers is common practice in the study of their physiology and related diseases. This review describes a common method of using an adaptable, low cost, semipermeable, suspended membrane to experimentally model three blood barriers in the human body: the blood-brain barrier (BBB), the gut-blood barrier (GBB), and the air-blood barrier (ABB). The GBB and ABB both protect from the outside environment, while the BBB protects the central nervous system from potential neurotoxic agents in the blood. These barriers share several commonalities, including the formation of tight junctions, polarized cellular monolayers, and circulatory system contact. Cell architectures used to mimic barrier anatomy as well as applications to study function, dysfunction, and response provide an overview of the versatility enabled by these cultural systems.

01 Dec 2023·Biomedicine & Pharmacotherapy

Decreased long-chain acylcarnitine content increases mitochondrial coupling efficiency and prevents ischemia-induced brain damage in rats

Article

Author: Svalbe, Baiba ; Sevostjanovs, Eduards ; Vavers, Edijs ; Grinberga, Solveiga ; Liepinsh, Edgars ; Dambrova, Maija ; Ozola, Melita ; Zvejniece, Liga ; Gukalova, Baiba

Long-chain acylcarnitines (LCACs) are intermediates of fatty acid oxidation and are known to exert detrimental effects on mitochondria. This study aimed to test whether lowering LCAC levels with the anti-ischemia compound 4-[ethyl(dimethyl)ammonio]butanoate (methyl-GBB) protects brain mitochondrial function and improves neurological outcomes after transient middle cerebral artery occlusion (MCAO). The effects of 14 days of pretreatment with methyl-GBB (5 mg/kg, p.o.) on brain acylcarnitine (short-, long- and medium-chain) concentrations and brain mitochondrial function were evaluated in Wistar rats. Additionally, the mitochondrial respiration and reactive oxygen species (ROS) production rates were determined using ex vivo high-resolution fluorespirometry under normal conditions, in models of ischemia-reperfusion injury (reverse electron transfer and anoxia-reoxygenation) and 24 h after MCAO. MCAO model rats underwent vibrissae-evoked forelimb-placing and limb-placing tests to assess neurological function. The infarct volume was measured on day 7 after MCAO using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Treatment with methyl-GBB significantly reduced the LCAC content in brain tissue, which decreased the ROS production rate without affecting the respiration rate, indicating an increase in mitochondrial coupling. Furthermore, methyl-GBB treatment protected brain mitochondria against anoxia-reoxygenation injury. In addition, treatment with methyl-GBB significantly reduced the infarct size and improved neurological outcomes after MCAO. Increased mitochondrial coupling efficiency may be the basis for the neuroprotective effects of methyl-GBB. This study provides evidence that maintaining brain energy metabolism by lowering the levels of LCACs protects against ischemia-induced brain damage in experimental stroke models.

01 Nov 2023·Open Biology

Spatio-temporal patterns of ovarian development and VgR gene silencing reduced fecundity in parthenogenetic Artemia

Article

Author: Du, Guoru ; Wang, Xuehui ; Duan, Hu ; Li, Ying ; Zhou, Jiaping ; Xiang, Jianhai ; Pan, Namin ; Sui, Liying ; Liu, Wei ; Shao, Xuanxuan

The halophilic zooplankton brine shrimp Artemia has been used as an experimental animal in multidisciplinary studies. However, the reproductive patterns and its regulatory mechanisms in Artemia remain unclear. In this study, the ovarian development process of parthenogenetic Artemia ( A. parthenogenetica ) was divided into five stages, and oogenesis or egg formation was identified in six phases. The oogenesis mode was assumed to be polytrophic. We also traced the dynamic translocation of candidate germline stem cells (cGSCs) using EdU labelling and elucidated several key cytological events in oogenesis through haematoxylin and eosin staining and fluorescence imaging. Distinguished from the ovary structure of insects and crustaceans, Artemia germarium originated from ovariole buds and are located at the base of the ovarioles. RNA-seq based on five stages of ovarian development identified 2657 upregulated genes related to reproduction by pair-to-pair comparison. Gbb , Dpp , piwi , vasa , nanos , VgA and VgR genes associated with cGSCs recognition and reproductive development were screened and verified using qPCR. Silencing of the VgR gene in A. parthenogenetica ( Ap-VgR ) at ovarian development Stage II led to a low level of gene expression (less than 10%) within 5 days, which resulted in variations in oogenesis-related gene expression and significantly inhibited vitellogenesis, impeded oocyte maturation, and eventually decreased the number of offspring. In conclusion, we have illustrated the patterns of ovarian development, outlined the key spatio-temporal features of oogenesis and identified the negative impacts of VgR gene knockdown on oogenesis using A. parthenogenetica as an experimental animal. The findings of this study also lay a foundation for the further study of reproductive biology of invertebrates.

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiovascular Diseases	Phase 1	LV	Grindeks AS	22 Feb 2020

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