FASEB bioAdvances最新文献

{"title":"An unidentified yet notable modification on INa and IK(DR) caused by ramelteon","authors":"Po-Ming Wu,&nbsp;Yi-Fang Tu,&nbsp;Hsin-Yen Cho,&nbsp;Meng-Cheng Yu,&nbsp;Yen-Hsien Wu,&nbsp;Sheng-Nan Wu","doi":"10.1096/fba.2024-00008","DOIUrl":"10.1096/fba.2024-00008","url":null,"abstract":"<p>Despite advancement in anti-seizure medications, 30% of patients continue to experience recurrent seizures. Previous data indicated the antiepileptic properties of melatonin and its agonists in several animal models. However, the underlying mechanisms of melatonin and its agonists on cellular excitability remain poorly understood. In this study, we demonstrated the electrophysiological changes of two main kinds of ion channels that are responsible for hyperexcitability of neurons after introduction of melatonin agonists- ramelteon (RAM). In Neuro-2a cells, the amplitude of voltage-gated Na⁺ (<i>I</i>_Na) and delayed-rectifier K⁺ currents (<i>I</i>_{K (DR)}) could be suppressed under RAM. The IC₅₀ values of 8.7 and 2.9 μM, respectively. RAM also diminished the magnitude of window Na⁺ current (<i>I</i>_{Na (W)}) elicited by short ascending ramp voltage, with unchanged the overall steady-state current–voltage relationship. The decaying time course of <i>I</i>_Na during a train of depolarizing pulses arose upon the exposure to RAM. The conditioning train protocol which blocked <i>I</i>_Na fitted the recovery time course into two exponential processes and increased the fast and slow time constant of recovery the presence of RAM. In pituitary tumor (GH₃) cells, <i>I</i>_Na amplitude was also effectively suppressed by the RAM. In addition, GH3-cells exposure to RAM decreased the firing frequency of spontaneous action potentials observed under current-clamp conditions. As a result, the RAM-mediated effect on INa was closely associated with its ability to decrease spontaneous action potentials. Collectively, we found the direct attenuation of <i>I</i>_Na and <i>I</i>_{K (DR)} caused by RAM besides the agonistic action on melatonin receptors, which could partially explain its anti-seizure activity.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 10","pages":"442-453"},"PeriodicalIF":2.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular TAS2Rs act as a gatekeeper for the excretion of harmful substances via ABCB1 in keratinocytes","authors":"Sazanami Mori,&nbsp;Natsuki Nakamura,&nbsp;Ayane Fuchigami,&nbsp;Satoshi Yoshimoto,&nbsp;Moe Sakakibara,&nbsp;Toshiyuki Ozawa,&nbsp;Junken Aoki,&nbsp;Asuka Inoue,&nbsp;Hayakazu Sumida,&nbsp;Hideya Ando,&nbsp;Motonao Nakamura","doi":"10.1096/fba.2024-00074","DOIUrl":"10.1096/fba.2024-00074","url":null,"abstract":"<p>Bitter taste receptors (TAS2Rs) are not only expressed in the oral cavity but also in skin. Extraoral TAS2Rs are thought to be involved in non-taste perception and tissue-specific functions. Keratinocytes that express TAS2Rs in the skin provide a first-line defense against external threats. However, the functional roles of these receptors in host defense remain unclear. Here, we demonstrated the sensory role of intracellularly located TAS2Rs against toxic substances in keratinocytes. Although many G protein-coupled receptors elicit signals from the surface, TAS2Rs were found to localize intracellularly, possibly to the ER, in human keratinocytes and HaCaT cells. TAS2R38, one of the TAS2R members, activated the G_α12/13/RhoA/ROCK/p38 MAP kinase/NF-κB pathway upon stimulation by phenylthiocarbamide (PTC), an agonist for this receptor, leading to the production of ABC transporters, such as ABCB1, in these cells. Notably, treatment with bitter compounds, such as PTC and saccharin, induced the upregulation of ABCB1 in HaCaT cells. Mechanistically, intracellular TAS2R38 and its downstream signaling G_α12/13/RhoA/ROCK/p38 MAP kinase/NF-κB pathway were identified to be responsible for the above effect. Pretreatment with PTC prevented the accumulation of rhodamine 123 because of its excretion via ABCB1. Furthermore, pretreatment with PTC or saccharin counteracted the effect of the toxic compound, diphenhydramine, and pretreated HaCaT cells were found to proliferate faster than untreated cells. This anti-toxic effect was suppressed by treatment with verapamil, an ABCB1 inhibitor, indicating that enhanced ABCB1 helps clear toxic substances. Altogether, harmless activators of TAS2Rs may be promising drugs that enhance the excretion of toxic substances from the human skin.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 10","pages":"424-441"},"PeriodicalIF":2.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidics—A novel technique for high-quality sperm selection for greater ART outcomes","authors":"Ghulam Rasool Bhat,&nbsp;Farooz Ahmad Lone,&nbsp;Jasmer Dalal","doi":"10.1096/fba.2024-00041","DOIUrl":"10.1096/fba.2024-00041","url":null,"abstract":"<p>Microfluidics represent a quality sperm selection technique. Human couples fail to conceive and this is so in a significant population of animals worldwide. Defects in male counterpart lead to failure of conception so are outcomes of assisted reproduction affected by quality of sperm. Microfluidics, deals with minute volumes (μL) of liquids run in small-scale microchannel networks in the form of laminar flow streamlines. Microfluidic sperm selection designs have been developed in chip formats, mimicking in vivo situations. Here sperms are selected and analyzed based on motility and sperm behavioral properties. Compared to conventional sperm selection methods, this selection method enables to produce high-quality motile sperm cells possessing non-damaged or least damaged DNA, achieve greater success of insemination in bovines, and achieve enhanced pregnancy rates and live births in assisted reproduction—in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Besides, the concentration of sperm available to oocyte can be controlled by regulating the flow rate in microfluidic chips. The challenges in this technology are commercialization of chips, development of fully functional species-specific microfluidic tools, limited number of studies available in literature, and need of thorough understanding in reproductive physiology of domestic animals. In conclusion, incorporation of microfluidic system in assisted reproduction for sperm selection may promise a great success in IVF and ICSI outcomes. Future prospectives are to make this technology more superior and need to modify chip designs which is cost effective and species specific and ready for commercialization. Comprehensive studies in animal species are needed to be carried out for wider application of microfluidic sperm selection in in vitro procedures.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 10","pages":"406-423"},"PeriodicalIF":2.5,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standing strong: War-related challenges in Ukrainian biomedical research and opportunities for support","authors":"Hubert Hondermarck,&nbsp;Nataliya Finiuk,&nbsp;Chen Chen Jiang,&nbsp;Rostyslav Stoika","doi":"10.1096/fba.2024-00072","DOIUrl":"10.1096/fba.2024-00072","url":null,"abstract":"<p>The prolonged war in Ukraine is having a strong impact on all sectors of the Ukrainian society, including biomedical research. Although the material and psychological conditions are challenging, the country and its researchers are courageously managing to continue their activities. This perspective paper describes the multiple challenges faced by Ukrainian biomedical researchers during wartime and outlines strategies to support and enhance collaboration with the global scientific community. Ukraine has a rich scientific history and modern expertise in biomedical research, and developing more international collaborations with Ukraine can have mutual benefits for all involved parties.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 10","pages":"401-405"},"PeriodicalIF":2.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo optical assessment of cerebral and skeletal muscle microvascular response to phenylephrine","authors":"Laura Mawdsley,&nbsp;Rasa Eskandari,&nbsp;Farah Kamar,&nbsp;Ajay Rajaram,&nbsp;Lawrence C. M. Yip,&nbsp;Naomi Abayomi,&nbsp;Stephanie Milkovich,&nbsp;Jeffrey J. L. Carson,&nbsp;Keith St. Lawrence,&nbsp;Christopher G. Ellis,&nbsp;Mamadou Diop","doi":"10.1096/fba.2024-00063","DOIUrl":"https://doi.org/10.1096/fba.2024-00063","url":null,"abstract":"<p>This study aimed to investigate the simultaneous response of the cerebral and skeletal muscle microvasculature to the same phenylephrine (PE) boluses. A hybrid optical system that combines hyperspectral near-infrared spectroscopy (hs-NIRS) and diffuse correlation spectroscopy (DCS) was used to monitor changes in tissue oxygenation and perfusion. Data were collected from the head and hind limb of seven male Sprague–Dawley rats while administering intravenous (IV) injections of PE or saline to all animals. The response to saline was used as a control. Skeletal muscle oxygenation decreased significantly after PE injection, while a statistically underpowered decrease in perfusion was observed, followed by an increase beyond baseline. Vascular conductance also decreased in the muscle reflecting the drug's vasoconstrictive effects. Tissue oxygenation and perfusion increased in the brain in response to PE. Initially, there was a sharp increase in cerebral perfusion but no changes in cerebral vascular conductance. Subsequently, cerebral flow and vascular conductance decreased significantly below baseline, likely reflecting autoregulatory mechanisms to manage the excess flow. Further, fitting an exponential function to the secondary decrease in cerebral perfusion and increase in muscular blood flow revealed a quicker kinetic response in the brain to adjust blood flow. In the skeletal muscle, PE caused a transient decrease in blood volume due to vasoconstriction, which resulted in an overall decrease in hemoglobin content and tissue oxygen saturation. Since PE does not directly affect cerebral vessels, this peripheral vasoconstriction shunted blood into the brain, resulting in an initial increase in oxygenated hemoglobin and oxygen saturation.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"390-399"},"PeriodicalIF":2.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human inborn errors of long-chain fatty acid oxidation show impaired inflammatory responses to TLR4-ligand LPS","authors":"Signe Mosegaard,&nbsp;Krishna S. Twayana,&nbsp;Simone W. Denis,&nbsp;Jeffrey Kroon,&nbsp;Bauke V. Schomakers,&nbsp;Michel van Weeghel,&nbsp;Riekelt H. Houtkooper,&nbsp;Rikke K. J. Olsen,&nbsp;Christian K. Holm","doi":"10.1096/fba.2024-00060","DOIUrl":"https://doi.org/10.1096/fba.2024-00060","url":null,"abstract":"<p>Stimulation of mammalian cells with inflammatory inducers such as lipopolysaccharide (LPS) leads to alterations in activity of central cellular metabolic pathways. Interestingly, these metabolic changes seem to be important for subsequent release of pro-inflammatory cytokines. This has become particularly clear for enzymes of tricarboxylic acid (TCA) cycle such as succinate dehydrogenase (<i>SDH</i>). LPS leads to inhibition of SDH activity and accumulation of succinate to enhance the LPS-induced formation of IL-1β. If enzymes involved in beta-oxidation of fatty acids are important for sufficient responses to LPS is currently not clear. Using cells from various patients with inborn long-chain fatty acid oxidation disorders (lcFAOD), we report that disease-causing deleterious variants of Electron Transfer Flavoprotein Dehydrogenase (<i>ETFDH</i>) and of Very Long Chain Acyl-CoA Dehydrogenase (<i>ACADVL</i>), both cause insufficient inflammatory responses to stimulation with LPS. The insufficiencies included reduced TLR4 expression levels, impaired TLR4 signaling, and reduced or absent induction of pro-inflammatory cytokines such as IL-6. The insufficient responses to LPS were reproduced in cells from healthy controls by targeted loss-of-function of either <i>ETFDH</i> or <i>ACADVL,</i> supporting that the deleterious <i>ETFDH</i> and <i>ACADVL</i> variants cause the attenuated responses to LPS. <i>ETFDH</i> and <i>ACADVL</i> encode two distinct enzymes both involved in fatty acid beta-oxidation, and patients with these deficiencies cannot sufficiently metabolize long-chain fatty acids. We report that genes important for beta-oxidation of long-chain fatty acids are also important for inflammatory responses to an acute immunogen trigger like LPS, which may have important implications for understanding infection and other metabolic stress induced disease pathology in lcFAODs.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"337-350"},"PeriodicalIF":2.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of nociception-sensitive ionotropic glutamate receptor-expressing rostroventrolateral medulla neurons by stimulation of cardiac afferents in rats","authors":"Matthew R. Zahner,&nbsp;Cade C. Oculam,&nbsp;Eric Beaumont","doi":"10.1096/fba.2024-00040","DOIUrl":"https://doi.org/10.1096/fba.2024-00040","url":null,"abstract":"<p>Myocardial ischemia causes the release of bradykinin, which activates afferent nerve endings in the ventricular epicardium. This elicits a sympathetically mediated increase in arterial pressure and heart rate, referred to as the cardiogenic sympathetic afferent reflex. The rostroventrolateral medulla (RVLM) is a key sympathetic brain stem site for regulating cardiovascular activity. This study aimed to determine the importance of non-barosensitive nociception sympathetic activity and the role of glutamate receptor activation of RVLM neurons in the cardiogenic sympathetic afferent reflex. We tested the hypothesis that inhibition of barosensitive sympathetic activity attenuates but does not abolish the reflex response to cardiac visceral afferents. Renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate responses to epicardial bradykinin application were recorded in anesthetized rats before and after bilateral RVLM microinjection of either GABA_A agonist muscimol, ionotropic glutamate receptor antagonist kynurenic acid, N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5- phosphonopentanoic acid (AP5), or non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Baroreceptor loading-induced inhibition of barosensitive activity attenuated the bradykinin-induced RSNA response (93 ± 14% increase) and tachycardia (18 ± 3 bpm). While RVLM muscimol microinjection abolished the RSNA response (1.6 ± 4.2% from baseline, 0.49 ± 0.38 μV*s), surprisingly, it did not abolish the tachycardia (27 ± 4 bpm). Kynurenic acid microinjection blocked the arterial pressure and RSNA responses, while AP5 or CNQX only attenuated the responses. These data suggest that nociception-sensitive sympathetic activity that does not appear to be barosensitive is also involved in the cardiogenic sympathetic afferent reflex. Importantly, while muscimol and kynurenic acid abolished the arterial pressure and RSNA response, neither affected the tachycardia, suggesting an alternate cardiac pathway independent of RVLM.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"377-389"},"PeriodicalIF":2.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteocalcin binds to a GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling","authors":"Rupesh Agarwal,&nbsp;Ruisong Ye,&nbsp;Micholas Dean Smith,&nbsp;Jeremy C. Smith,&nbsp;L. Darryl Quarles,&nbsp;Min Pi","doi":"10.1096/fba.2024-00025","DOIUrl":"https://doi.org/10.1096/fba.2024-00025","url":null,"abstract":"<p>GPRC6A, a member of the Family C G-protein coupled receptors, regulates energy metabolism and sex hormone production and is activated by diverse ligands, including cations, L-amino acids, the osteocalcin (Ocn) peptide and the steroid hormone testosterone. We sought a structural framework for the ability of multiple distinct classes of ligands to active GPRC6A. We created a structural model of GPRC6A using Alphafold2. Using this model we explored a putative orthosteric ligand binding site in the bilobed Venus fly trap (VFT) domain of GPRC6A and two positive allosteric modulator (PAM) sites, one in the VFT and the other in the 7 transmembrane (7TM) domain. We provide evidence that Ocn peptides act as a PAM for GPRC6A by binding to a site in the VFT that is distinct from the orthosteric site for calcium and L-amino acids. In agreement with this prediction, alternatively spliced GPRC6A isoforms 2 and 3, which lack regions of the VFT, and mutations in the computationally predicted Ocn binding site, K352E and H355P, prevent Ocn activation of GPRC6A. These observations explain how dissimilar ligands activate GPRC6A and set the stage to develop novel molecules to activate and inhibit this previously poorly understood receptor.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"365-376"},"PeriodicalIF":2.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G protein coupled receptor in apoptosis and apoptotic cell clearance","authors":"Xinyan Li,&nbsp;Chao Li,&nbsp;Yang Kang,&nbsp;Rui Zhang,&nbsp;Peiyao Li,&nbsp;Qian Zheng,&nbsp;Hui Wang,&nbsp;Hui Xiao,&nbsp;Lei Yuan","doi":"10.1096/fba.2024-00067","DOIUrl":"https://doi.org/10.1096/fba.2024-00067","url":null,"abstract":"<p>Apoptosis is a genetically programmed form of cell death that is substantially conserved across the evolutionary tree. Apoptotic cell elimination includes recognition, phagocytosis, and degradation. Failure to clear apoptotic cells can ultimately cause a series of human diseases, such as systemic lupus erythematosus, Alzheimer's disease, atherosclerosis, and cancer. Consequently, the timely and effective removal of apoptotic cells is crucial to maintaining the body's homeostasis. GPCRs belong to the largest membrane receptor family. Its intracellular domain exerts an effect on the trimer G protein. By combining with a variety of ligands, the extracellular domain of G protein initiates the dissociation of G protein trimers and progressively transmits signals downstream. Presently, numerous G protein-coupled receptors (GPCRs) have been identified as participants in the apoptosis signal transduction pathway and the apoptotic cell clearance pathway. Therefore, studies on the mechanism of GPCRs in the clearance of apoptotic cells is important for the development of GPCRs therapeutics.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"289-297"},"PeriodicalIF":2.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights on pathophysiology of hydrocephalus rats induced by kaolin injection","authors":"Kuo Zhang,&nbsp;Wanqi Zhou,&nbsp;Huijie Yu,&nbsp;Meijun Pang,&nbsp;Huixin Gao,&nbsp;Faheem Anwar,&nbsp;Kai Yu,&nbsp;Ziwei Zhou,&nbsp;Fang Guo,&nbsp;Xiuyun Liu,&nbsp;Dong Ming","doi":"10.1096/fba.2024-00070","DOIUrl":"https://doi.org/10.1096/fba.2024-00070","url":null,"abstract":"<p>Hydrocephalus can affect brain function and motor ability. Current treatments mostly involve invasive surgeries, with a high risk of postoperative infections and failure. A successful animal model plays a significant role in developing new treatments for hydrocephalus. Hydrocephalus was induced in Sprague–Dawley rats by injecting 25% kaolin into the subarachnoid space at the cerebral convexities with different volumes of 30, 60 and 90 μL. Magnetic resonance imaging (MRI) was performed 1 month and 4 months after kaolin injection. The behavioral performance was assessed weekly, lasting for 7 weeks. The histopathological analyses were conducted to the lateral ventricles by hematoxylin–eosin (HE) staining. Transcriptomic analysis was used between Normal Pressure Hydrocephalus (NPH) patients and hydrocephalus rats. MRI showed a progressive enlargement of ventricles in hydrocephalus group. Kaolin-60 μL and kaolin-90 μL groups showed larger ventricular size, higher anxiety level, bigger decline in body weight, motor ability and cognitive competence. These symptoms may be due to higher-grade inflammatory infiltrate and the damage of the structure of ependymal layer of the ventricles, indicated by HE staining. The overlap upregulated genes and pathways mainly involve immunity and inflammation. Transcriptomic revealed shared pathogenic genes CD40, CD44, CXCL10, and ICAM1 playing a dominance role. 60 μL injection might be recommended for the establishment of hydrocephalus animal model, with a high successful rate and high stability. The hydrocephalus model was able to resemble the inflammatory mechanism and behavioral performance observed in human NPH patients, providing insights for identifying therapeutic targets for hydrocephalus.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"6 9","pages":"351-364"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}