Rat Model Of Injury Research Articles

A Self-Gelling Powder Based on Polyacrylic Acid/Polyethyleneimine/Polyethylene Glycol for High-Performance Hemostasis and Antibacterial Activity

Powder-based hemostatic materials have offered unprecedented opportunities for the effective sealing and repair of irregularly shaped wounds and high-pressure, noncompressible arterial bleeding wounds caused by surgeries, traffic accidents, and wartime injuries. However, inadequate adhesion to bleeding wounds and poor hemostasis in biological tissues remains challenging. Herein, we report a self-gelling hemostatic powder based on polyacrylic acid/polyethyleneimine/polyethylene glycol (named PPG) for rapid hemostasis and effective antibacterial ability. When deposited on bleeding wounds, PPG powder can absorb interfacial liquid and rapidly swell into a physically cross-linked hydrogel in situ within 2 s to form a pressure-resistant physical barrier. Furthermore, the in vivo and in vitro results indicate that, as an effective sealant, the PPG powder possesses ease of use, excellent hemocompatibility, strong antibacterial abilities, and superior blood clotting abilities. The effective hemostatic sealing capability of the PPG powder is demonstrated in a variety of injury models in rats and rabbits. All of these factors show that, with its superior wound treatment abilities, PPG powder is a profound biomaterial for surgical applications.

SIRT1 Activation Suppresses Corneal Endothelial–Mesenchymal Transition via the TGF-β/Smad2/3 Pathway

Endothelial–mesenchymal transition (EnMT) is the transversion of endothelial cells to mesenchymal cells under certain physiological or pathological conditions. When EnMT occurs in the corneal endothelium, corneal endothelial cells (CECs) lose their normal function and thus cannot maintain corneal clarity. Studies have shown that the mechanism of EnMT in CECs involves the transforming growth factor-β (TGF-β) signaling pathway, and one of the important inhibitors of the TGF-β/Smad2/3 pathway is sirtuin-1 (SIRT1). In this study, we used a rat model of corneal endothelium injury and TGF-β1-treated human CECs to induce EnMT, aiming to explore whether SIRT1 activation inhibits corneal EnMT in vivo and in vitro. SIRT1 was activated and suppressed using resveratrol (RSV) and EX527, respectively. The endothelial markers and mesenchymal markers were measured by immunofluorescence and Western blot assays. Co-immunoprecipitation was used to detect the interaction between SIRT1 and Smad2/3. The results showed that after mechanical injury, the group treated with RSV-activated SIRT1 regained corneal transparency and recovered from edema faster than the control group. Moreover, RSV-activated SIRT1 downregulated the expression levels of alpha smooth muscle actin (α-SMA), vimentin, and Snail and upregulated the expression levels of E-cadherin and Na+/K+-ATPase both in vivo and in vitro, but these effects were reversed when SIRT1 was inhibited by EX527. SIRT1 also upregulated the expression levels of TGF-β receptor 1 and phosphorylated Smad2/3. The interaction between SIRT1 and Smad2/3 in vitro was confirmed by co-immunoprecipitation. Overall, our results indicate that SIRT1 activation inhibits corneal EnMT via the TGF-β/Smad2/3 pathway, which may be a potential therapeutic target for corneal endothelium dysfunction.

Pulsed radiofrequency alleviates neuropathic pain by upregulating MG53 to inhibit microglial activation

BackgroundPatients with neuropathic pain (NP) have significantly lower quality of life. Because the pathophysiology of NP is not fully understood, there is a lack of effective treatment for it in clinic. This study set out to investigate the precise mechanism by which pulsed radiofrequency (PRF) alleviated NP.MethodThe rat models of chronic constriction injury of the sciatic nerve (CCI) were established to simulate the occurrence of NP, following with measuring MWT and TWL to evaluate the pain of the rats. HE staining was utilized to observe the rat spinal cord tissue pathology. The expression of MG53, ATF4 and CHOP was evaluated by qRT-PCR and WB, while the expression of inflammatory factors was measured by ELISA. In addition, immunofluorescence assay was used to detect the expression of MG53 and Iba-1.ResultPRF treatment alleviated NP in CCI rats, as well as upregulating the expression of MG53 and inhibiting microglial activation. After MG53 knockdown, the remission of NP by PRF was significantly weakened, but microglial activation and endoplasmic reticulum stress (ERS) exhibited enhancement. Therefore, PRF inhibited microglial activation by upregulating MG53. After injection of ERS inducer in CCI rats, the inhibition effect of overexpressed MG53 on microglial activation and its alleviation effect on NP were reversed. Consequently, MG53 played a role in suppressing microglial activation by mediating the inhibition of ERS.ConclusionPRF attenuated microglial activation by upregulating MG53 to inhibit ERS, resulting in the alleviation of NP in CCI rats.

Pharmacokinetics and brain uptake of sodium selenate and selenium in naïve rats and a lateral fluid percussion injury ratmodel.

Post-traumatic epilepsy (PTE) is a life-long complication of traumatic brain injury (TBI). The development of PTE is associated with neurological morbidity and increases the risk of mortality. An aim of EpiBioS4Rx (Epilepsy Bioinformatics Study for Antiepileptogenic Therapy) was to test potential therapies to prevent the development of PTE in the lateral fluid percussion injury (LFPI) rat model of TBI, in which rats were subjected to injury at the left parietal cortex. Sodium selenate has been reported to be antiepileptogenic post-TBI in rodent models by activating protein phosphatase 2A and reducing phosphorylated tau (p-tau) protein. We aimed to characterize the pharmacokinetics (PK) and brain uptake of sodium selenate using naïve control and LFPI rats. Rats received either a single bolus dose or a single bolus dose followed by a 7-day subcutaneous minipump infusion of sodium selenate. Sodium selenate and selenium concentrations in plasma and brain were analyzed and used for PK estimation and brain exposure assessment. Selenium concentrations rapidly increased after sodium selenate administration, demonstrating biotransformation from sodium selenate to selenium. Sodium selenate and selenium PK parameters were estimated using non-compartmental analysis. Sodium selenate clearance (CL/F) and volume of distribution (Vd/F) varied by dose and route of administration, suggesting differences in bioavailability and nonlinear pharmacokinetics at the doses tested. Brain-to-plasma partition coefficients (AUCbrain/AUCplasma) for sodium selenate and selenium were found to be 0.7-1.3 and 0.1-0.3 following single-dose injection, respectively, indicating active transport of sodium selenate across the blood-brain barrier (BBB).

Sex differences in the affective-cognitive dimension of neuropathic pain: Insights from the Spared Nerve Injury rat model

Over 40% of neuropathic pain patients experience mood and cognitive disturbances, often showing reduced response to analgesics, with most affected individuals being female. This highlights the critical role of biological sex in pain-related affective and cognitive disorders, making it essential to understand the emotional and cognitive circuits linked to pain for improving treatment strategies. However, research on sex differences in preclinical pain models is lacking. This study aimed to investigate these differences using the spared nerve injury (SNI) rat model, conducting a comprehensive series of behavioural tests over 100 days post-injury to identify key time points for observing sex-specific behaviours indicative of pain-related conditions. The findings revealed that female rats exhibited greater mechanical and cold hypersensitivity compared to males following nerve injury and showed earlier onset of depression-related behaviours, while males were more prone to anxiety, social, and memory-related alterations. Interestingly, by the 14th week post-injury, females displayed no signs of these emotional and cognitive impairments. Additionally, fluctuations in the oestrous cycle or changes in testosterone and oestradiol levels did not correlate with sex differences in pain sensitivity or negative affect. Recognizing the influence of biological sex on pain-induced affective and cognitive alterations, especially in later stages post-injury, is crucial for enhancing our understanding of this complex pain disorder. Data availabilityAccess to the raw data constituting the findings presented in this manuscript can be requested from the corresponding author of the publication.

Tanshinone IIA attenuates fluoride-induced spinal cord injury by inhibiting ferroptosis and inflammation

Excessive fluoride exposure can lead to health problems, such as fluorosis and neurotoxicity. However, effective therapeutic strategies for neurofluorosis remain elusive due to a limited understanding of the underlying molecular mechanisms. This study aimed to investigate the effects of Tanshinone IIA on spinal cord injury induced by high-fluoride exposure. To identify dysregulated genes associated with ferroptosis, we conducted an intersection analysis between differentially expressed genes in fluoride-treated HOS cells (GSE70719) and ferroptosis-related genes from the FerrDb database. A rat model of fluoride-induced spinal cord injury was established, revealing evidence of aberrant molecular and structural changes. Furthermore, the study demonstrated that Tanshinone IIA restored the altered expression of nine ferroptosis-related genes, eight fluorosis-related inflammatory indicators, and the observed structural changes. Overall, these findings suggest that Tanshinone IIA therapeutic potential in the treatment of fluoride-induced spinal cord injury by inhibiting ferroptosis and inflammation.

Inhibition of peritendinous adhesion through targeting JAK2-STAT3 signaling pathway: The therapeutic potential of AG490

Peritendinous adhesion is a common complication following tendon injury repair, posing a significant clinical challenge that requires urgent attention. The primary cause of peritendinous adhesion is the excessive deposition of collagen matrix due to the abnormal proliferation of fibroblasts in an inflammatory state. Janus kinase2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) are key signaling molecules involved in cell proliferation and fibrosis development in various organs. However, the role of the JAK-2 and STAT3 signaling pathways in peritendinous adhesion fibrosis remains unclear. In our study, we first observed upregulation of p-JAK2 and p-STAT3 proteins in human peritendinous adhesion specimens and rat peritendinous adhesion models. In vitro, the JAK2/STAT3 pathway inhibitor AG490 effectively inhibited TGF-β1-induced fibroblast proliferation. Wound healing and transwell assays demonstrated that AG490 suppressed TGF-β1-induced fibroblast migration. Furthermore, we found that AG490 decreased the expression of pro-inflammatory factors, including IL-1β and TNF-α, as well as extracellular matrix (ECM) proteins in fibroblasts under TGF-β1 stimulation. In vivo, histological staining showed that AG490 prevented fibrous tissue formation in a rat model of tendon injury. Moreover, AG490 inhibited the overexpression of pro-inflammatory factors IL-1β and TNF-α, as well as ECM in the peritendinous adhesions. In conclusion, AG490 inhibited fibrosis and inflammation in injured tendons by targeting the JAK2-STAT3 signaling pathway, presenting a promising strategy for the prophylaxis of peritendinous adhesions.

Mechanistic insights into “Three Methods and Three Acupoints” Tuina therapy for improving spinal microcirculation and motor function in sciatic nerve injury model rats

Mechanistic insights into “Three Methods and Three Acupoints” Tuina therapy for improving spinal microcirculation and motor function in sciatic nerve injury model rats

The Role of Panax Notoginseng Saponins on Neuronal Oxidative Stress and Autophagy Response in Craniocerebral Injury Model Rats

This study assessed how IL-6 affects the body’s autophagy status by regulating JAK-STAT3 and explored the mechanism by which IL-6 inhibits JAK-STAT3 signaling pathway-mediated autophagy, and how Panax notoginseng total saponins promote neuronal cell regeneration in rats. A model of neuronal oxidative stress in craniocerebral injury model rats was established, and IL-6 levels were detected by ELISA. Rat neuronal cells were isolated and cultured, while dual-luciferase gene reporter experiments analyzed the targeting relationship between IL-6 and JAK. qRT-PCR detected expression of neuronal autophagy-related genes (JAK, STAT3, ULK1, OsATG7, FAM176A, and Beclin 1). The level of IL-6 in the craniocerebral injury model was significantly higher than that in the control group. IL-6 binds to 3′-UTR of JAK, and transfection with IL-6 inhibitor increases the relative luciferase activity. pMIR-JAK-mut group has no significant effect. There is a targeted regulatory relationship between IL-6 and JAK. Adding total saponins of Panax notoginseng combined with nursing intervention can promote reduction genetic expression related to neuronal autophagy damage. IL-6 can target and regulate JAK gene. IL-6 can promote neuronal development by regulating JAK-STAT3. Autophagy repairs damage and inhibits the autophagy state of cells. Panax notoginseng total saponins are effective medicinal components extracted from high quality panax notoginseng according to extraction and separation technology. The results from this study provide a better understanding of pathogenesis of neuronal oxidative stress in craniocerebral injury model rats and find potential intervention targets, which will provide more treatment methods for neuronal oxidative stress damage in craniocerebral injury model rats.

Induction of Neural Differentiation and Protection by a Novel Slow-Release Nanoparticle Estrogen Construct in a Rat Model of Spinal Cord Injury

Spinal cord injury (SCI) is a complex debilitating condition leading to permanent life-long neurological deficits. Estrogen (E2) treatment is known to be neuroprotectant in SCI. This hormone is highly pleiotropic and has been shown to decrease apoptosis, modulate calcium signaling, regulate growth factor expression, act as an anti-inflammatory, and drive angiogenesis. These beneficial effects were found in our earlier study at the low dose of 10 µg/kg E2 in rats. However, the dose remains non-physiologic, which poses a safety hurdle for clinical use. Thus, we recently devised/constructed a fast release nanoparticle (NP) estrogen embedded (FNP-E2) construct and tested a focal delivery system in a contused SCI rat model which showed protection in the short run. In the current study, we have developed a novel slow-release NP estrogen (SNP-E2) delivery system that shows sustained release of E2 in the injured spinal cord and no systemic exposure in the host. The study of E2 release and kinetics of this SNP-E2 construct in vitro and in vivo supported this claim. Delivery of E2 to the injured spinal cord via this approach reduced inflammation and gliosis, and induced microglial differentiation of M1 to M2 in rats after SCI. Analysis of spinal cord samples showed improved myelination and survival signals (AKT) as demonstrated by western blot analysis. SNP-E2 treatment also induced astrocytic differentiation into neuron-like (MAP2/NeuN) cells, supported the survival of oligodendrocyte precursor cells (OPC), and improved bladder and locomotor function in rats following SCI. These data suggest that this novel delivery strategy of SNP-E2 to the injured spinal cord may provide a safe and effective therapeutic approach to treat individuals suffering from SCI.

Attenuating Cartilage Degeneration in a Low Mechanical Compression Rat Model Through Intra-Articular Injections of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells.

Mechanical stimulation significantly contributes to posttraumatic osteoarthritis (PTOA), a condition that impedes patient recovery following intra-articular injury. Effective treatment options for compression-induced injuries are limited. Bone marrow-derived mesenchymal stem cell (BMSC) implantation has emerged as a potential therapeutic breakthrough for joint diseases. The aim of this study was to attenuate the progression of PTOA induced by cyclic loading and demonstrate the potential effectiveness of BMSCs in a rat model of low mechanical compression. Using a rat model of compression-induced articular cartilage injury, assessments were conducted 2, 4, and 8 weeks after cyclic compressive loading. The expression of matrix metallopeptidase 13, transforming growth factor-beta 3 (TGF-β3), insulin-like growth factor 1 (IGF-1), and cleaved caspase-3 was evaluated through immunohistochemistry to investigate the mechanistic aspects underlying the prevention of compression-induced injury following BMSCs treatment. Intra-articular injections of BMSCs significantly improved scores in the OARSI (Osteoarthritis Research Society International) Osteoarthritis Cartilage Histopathology Assessment System and Histological-Histochemical Grading System. This treatment showed positive outcomes in maintaining high relative cell density and reducing proteoglycan loss after cyclic compression-induced injury. The expression patterns of IGF-1 and TGF-β3 provide valuable insights into the presence and distribution of these growth factors in healthy and injured cartilage. These findings highlight the efficacy of BMSCs treatment in attenuating the advancement of compression-induced injuries, albeit within a limited timeframe.

Minimally invasive serial collection of cerebrospinal fluid reveals sex-dependent differences in neuroinflammation in a rat model of mild traumatic brain injury

Traumatic brain injuries (TBI) are the seventh leading cause of disability globally with 48.99 million prevalent cases and 7.08 million years lived with diability. Approximately 80 % of TBI patients are diagnosed with mild TBI (mTBI), or concussion, caused by nonpenetrating mechanical trauma to the head or body along with sudden rotational motion of the head. Studies investigating the temporal dynamics of neuroinflammation after mTBI are greatly needed. Without longitudinal studies, translating preclinical studies to clinical studies remains challenging as the difference in timing remains poorly understood. In this study, we describe a method of minimally invasive serial cerebrospinal fluid (CSF) collection that enables longitudinal investigation of CSF inflammation. The method described in this study can easily be adapted by any laboratory prepared for animal studies. Multiplex immunoassay of serially collected and singly collected CSF samples show collection frequency does not alter protein expression in the CSF. Further, sex-dependent differences in TBI have been reported, but remain poorly understood. This study establishes a framework for assessing sex difference in neuroinflammation after a concussion. We showed that results vary based on the framing of the statistical test. However, it is evident that males experience a more robust inflammatory response to a single concussion than females.

OrthologAL: A Shiny application for quality-aware humanization of non-human pre-clinical high-dimensional gene expression data.

Single-cell and spatial transcriptomics provide unprecedented insight into the inner workings of disease. Pharmacotranscriptomic approaches are powerful tools that leverage gene expression data for drug repurposing and treatment discovery in many diseases. Multiple databases attempt to connect human cellular transcriptional responses to small molecules for use in transcriptome-based drug discovery efforts. However, pre-clinical research often requires in vivo experiments in non-human species, which makes capitalizing on such valuable resources difficult. To facilitate the application of pharmacotranscriptomic databases to pre-clinical research models and to facilitate human orthologous conversion of non-human transcriptomes, we introduce OrthologAL. OrthologAL leverages the BioMart database to access different gene sets from Ensembl, facilitating the interaction between these servers without needing user-generated code. Researchers can input their single-cell or other high-dimensional gene expression data from any species, and OrthologAL will output a human ortholog-converted dataset for download and use. To demonstrate the utility of this application, we characterized orthologous conversion in single-cell, single-nuclei, and spatial transcriptomic data derived from common pre-clinical models, including patient-derived orthotopic xenografts of medulloblastoma, and mouse and rat models of spinal cord injury. We show that OrthologAL can convert these data types efficiently to that of corresponding orthologs while preserving the dimensional architecture of the original non-human expression data. OrthologAL will be broadly useful for applying pre-clinical, high-dimensional transcriptomics data in functional small molecule predictions using existing human-annotated databases.

Anti-neuropathic effects of astaxanthin in a rat model of chronic constriction injury: passing through opioid/benzodiazepine receptors and relevance to its antioxidant and anti-inflammatory effects.

Neuropathic pain is a debilitating neurological disorder and is on the rise. Since no effective treatment has been so far approved to combat the complex pathological mechanisms behind neuropathic pain, finding new therapeutic candidates is of great importance. Astaxanthin (AST) is a carotenoid with strong antioxidant, and anti-inflammatory activities. The present research aimed to evaluate the ameliorative effects of AST on a rat model of neuropathic pain. To induce neuropathic pain, a chronic constriction injury (CCI) model was employed. Accordingly, Wistar rats were divided into nine groups of six including sham, negative control group (CCI), positive control group gabapentin (100mg/kg), AST (5, 10mg/kg), flumazenil (0.5mg/kg), naloxone (0.1mg/kg), AST (10mg/kg) + flumazenil (0.5mg/kg), and AST (10mg/kg) + naloxone (0.1mg/kg) were administered intraperitoneally on days 1, 3, 5, 7, 10, and 14. To check the experimental signs of neuropathic pain and motor dysfunction, hot plate, acetone drop, and open field tests were used at the same time points. Additionally, biochemical assay and zymography were done on days 7 and 14 to assess the changes in catalase, glutathione and nitrite, as well as matrix metalloproteinases (MMP-2 and MMP-9). Besides, histological evaluations were performed for tissue damages on days 7 and 14. Results indicated that intraperitoneal injection of AST improved allodynia, hyperalgesia, and locomotor activity after CCI. AST also increased catalase and glutathione while suppressing nitrite, MMP-2, and MMP-9 activity through opioid/benzodiazepine receptors. The results highlighted AST as a promising candidate against neuropathic pain with beneficial effects on motor function by suppressing inflammatory mediators, and augmenting antioxidant factors, passing through opioid/benzodiazepine receptors.

Spinal cord stimulation induces Neurotrophin-3 to improve diabetic foot disease.

Low-extremity ischemic disease is a common complication in diabetic patients, leading to reduced quality of life and potential amputation. This study investigated the therapeutic effect of spinal cord stimulation (SCS) on patients with diabetic foot disease and a rat model of diabetic foot injury. SCS was applied to patients with diabetic foot disease, with clinical assessments performed before and after therapy. Blood levels of NGF, BDNF, and NT-3 were determined by ELISA. A rat model of diabetic foot injury was established to validate NT-3's role in SCS therapy. SCS therapy improved the condition of patients with diabetic ischemic foot disease and promoted wound healing in the rat model. NT-3 levels significantly increased after SCS therapy in both patients and rats. Recombinant NT-3 administration improved wound healing and re-vascularization in the rat model, while NT-3 neutralization abrogated SCS's therapeutic effect. SCS improves the condition of patients with diabetic ischemic foot disease by inducing NT-3 production. Both SCS and NT-3 supplementation show therapeutic potential for ameliorating diabetic foot disease.

Spinal cord neural stem cells derived from human embryonic stem cells promote synapse regeneration and remyelination in spinal cord injury model rats.

Spinal cord injury (SCI) is a devastating injury that significantly impairs patients' quality of life. To date, there is no effective treatment to mitigate nerve tissue damage and restore neurological function. Neural stem cells (NSCs) derived from human embryonic stem cells (hESCs) are considered an important cell source for reconstructing damaged neural circuits and enabling axonal regeneration. Recent preclinical studies have shown that NSCs are potential therapeutic cell sources for neuroprotection and neuroregeneration in SCI animal models. NSCs can be derived from different sources and the spinal cord-specific NSCs have a higher potential for the regeneration of SCI. However, the long-term therapeutic efficacy of spinal cord-specific NSCs remains unproven. Here, we generated human spinal cord NSCs (hSCNSCs) and investigated the effects of transplanted hSCNSCs on the repair of the SCI model rats for 60 days. The transplanted hSCNSCs improved BBB scores, reduced the lesion area and promoted an increase in the number of Nestin-positive cells in the spinal cord compared to the model rats. Meanwhile, hSCNSC transplantation promoted the expression of synaptophysin, a synaptic signature protein and MBP, a protein associated with remyelination. Interestingly, BAF45D, a chromatin remodelling factor that contributes to the induction of hSCNSCs with region-specific spinal cord identity, were increased by the hSCNSC transplantation. In addition, conditioned medium derived from the hSCNSCs also promoted regenerative repair of the injured spinal cord. These results demonstrate that hSCNSCs may play a critical role in the regenerative repair of SCI.

Astragaloside IV Inhibits Lung Injury and Fibrosis Induced by PM2.5 by Targeting RUNX1 Through miR-362-3p.

To discover the molecular mechanism of Astragaloside IV (AS IV) in PM2.5-induced lung injury and pulmonary fibrosis (PF). A lung injury rat model was induced by PM2.5 and injected intraperitoneally with AS IV. Lungs were harvested to evaluate lung tissue injury and apoptosis. Rat alveolar epithelial cells L2 were exposed to PM2.5 and treated with AS IV. After cellular transfection, cell proliferation, LDH production, and apoptosis were measured. In both models, inflammatory factors and fibrotic indices were measured by ELISA and Western blot. miR-362-3p and RUNX1 interplay was explored and confirmed. Administration of AS IV attenuated PM2.5-induced lung tissue injury, inflammation, apoptosis, and PF in rats. AS IV enhanced proliferation and reduced LDH release, apoptosis, inflammation, and PF in PM2.5-treated L2 cells. MiR-362-3p upregulation improved PM2.5-induced L2 cell injury. AS IV improved PM2.5-induced lung injury by upregulating miR-362-3p. miR-362-3p had an inhibition effect on RUNX1 expression. RUNX1 upregulation weakened the therapeutic effect of AS IV on PM2.5-induced alveolar epithelial cell injury. AS IV inhibits lung injury and PF induced by PM2.5 by targeting RUNX1 through upregulation of miR-362-3p.

Neuroprotective Effects of Ethanol Extract Polyscias guilfoylei (EEPG) Against Glutamate Induced Neurotoxicity in HT22 Cells.

Oxidative stress induced by glutamate is a significant contributor to neuronal cell damage and can lead to neurodegenerative diseases such as Alzheimer's, Huntington's, and ischemic brain injury. At the cellular level, oxidative stress increases Ca2+ ion influx and reactive oxygen species (ROS), which activate the MAPK signaling pathway. Additionally, the generation of ROS causes mitochondrial dysfunction, triggering apoptosis by promoting the translocation of AIF to the nucleus from the mitochondria. The neuroprotective potential of Polyscias guilfoylei has not yet been reported. Therefore, in this study, the ethanol extract of Polyscias guilfoylei (EEPG) was examined for its protective effect against oxidative cell damage caused by glutamate in neuronal cells. EEPG treatment increased the viability of HT22 cells exposed to high concentrations of glutamate. Cellular Ca2+ ion influx and ROS generation decreased with EEPG treatment in glutamate-treated HT22 cells. EEPG treatment inhibited MAPK activation and AIF nuclear translocation. In an in vivo study, EEPG attenuated brain cell death in an ischemic brain injury rat model. This study demonstrates the potential therapeutic effects of Polyscias guilfoylei in the treatment of ischemic brain injury.

Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats.

In the United States, traumatic brain injury (TBI) contributes significantly to mortality and morbidity. Elovanoids (ELVs), a novel class of homeostatic lipid mediators we recently discovered and characterized, have demonstrated neuroprotection in experimental stroke models but have never been tested after TBI. A moderate fluid-percussion injury (FPI) model was used on male rats that were treated with ELVs by intravenous (IV) or intranasal (IN) delivery. In addition, using liquid chromatography-mass spectrometry (LC-MS/MS), we examined whether ELVs could be detected in brain tissue after IN delivery. ELVs administered intravenously 1 h after FPI improved behavior on days 2, 3, 7, and 14 by 20, 23, 31, and 34%, respectively, and preserved hippocampal CA3 and dentate gyrus (DG) volume loss compared to the vehicle. Whole-brain tractography revealed that ELV-IV treatment increased corpus callosum white matter fibers at the injury site. In comparison to treatment with saline on days 2, 3, 7, and 14, ELVs administered intranasally at 1 h and 24 h after FPI showed improved neurological scores by 37, 45, 41, and 41%. T2-weighted imaging (T2WI) abnormalities, such as enlarged ventricles and cortical thinning, were reduced in rats treated by ELV-IN delivery compared to the vehicle. On day 3, ELVs were detected in the striatum and ipsilateral cortex of ELV-IN-treated rats. We have demonstrated that both ELV-IN and ELV-IV administration offer high-grade neuroprotection that can be selectively supplied to the brain. This discovery may lead to innovative therapeutic targets for secondary injury cascade prevention following TBI.

Regional variations in hyperpolarized 129Xe lung MRI: Insights from CSI-CSSR and CSSR in healthy and irradiated rat models.

To compare pulmonary function metrics obtained with hyperpolarized xenon-129 (HXe) MRS, using chemical shift saturation recovery (CSSR) and CSI-CSSR, in healthy rats and a rat model of radiation-induced lung injury. HXe-MR data were acquired in two healthy rats and one rat with radiation-induced lung injury using whole-lung spectroscopy and CSI-CSSR techniques. The CSI-CSSR acquisitions were performed with both fixed TE and variable TE. Apparent alveolar septal wall thickness, gas transfer dynamics, and regional lung function were quantified and compared across acquisition methods. Spectral analysis included alignment of dissolved-phase frequency spectra using the membrane resonance as reference, segmentation of gas-phase (GP) frequency distribution, and characterization of gas uptake in the vasculature. Complex GP line shapes were observed in rat lungs, necessitating pixel-wise CSI analysis and membrane resonance alignment for improved quantification. Notable differences in alveolar septal wall thickness, dissolved-phase GP ratios, and GP and red blood cell frequencies were found between acquisition techniques and lung conditions. CSI-CSSR provided unique insights into regional lung function, including the identification of distinct GP frequency zones potentially corresponding to different airway structures, and the ability to map relative xenon gas transport. Metrics from fixed-TE and variable-TE acquisitions usually differed by less than 10%, but the latter yielded a 20% SNR gain. HXe-MRS and CSI-CSSR techniques provide similar but not universally interchangeable insights into lung function, particularly in the presence of pathology.