Rat Model Of Injury Research Articles

Safe subdural administration and retention of a neurotrophin-3-delivering hydrogel in a rat model of spinal cord injury

Neurotrophic growth factor (GF) loaded hydrogels have shown promise as a treatment approach for spinal cord injury (SCI). However, SCI presents complex challenges for the direct administration of treatment due to the spinal cord’s intricate anatomy and highly sensitive environment. Many current hydrogel administration approaches overlook this complexity, limiting their translational potential. To address this, we propose a novel intrathecal administration method using an in situ gelling, hyaluronic acid-modified heparin-poloxamer hydrogel loaded with neurotrophin-3 (NT-3) for the direct delivery of NT-3 to the spinal cord. We injected a NT-3 loaded hydrogel into the intrathecal space immediately after contusion SCI in Sprague Dawley (SpD) rats. Our results indicate that injecting the NT-3 loaded hydrogel into the intrathecal space was safe and that the gel was retained alongside the cord for at least one week. Additionally, no adverse effects were observed on rat behaviour. While functional improvement trends were noted, statistical significance was not reached, and immunohistochemistry results showed no significant difference between treatment groups. Overall, our findings suggest the feasibility, safety, and potential of the developed intrathecal administration technique for delivering diverse therapeutic molecules for SCI recovery.

Pedal Reaction Forces and Electromyography Responses Indicate Eccentric Contractions During Motorized Cycling in a Rat Model of Incomplete Spinal Cord Injury.

Motorized cycling (MC) is utilized as an alternative to traditional exercise in individuals who are unable to perform voluntary movements post-spinal cord injury. Although rodent models of MC often show more positive outcomes when compared with clinical studies, the cause of this difference is unknown. We postulate that biomechanical differences between rats and humans may contribute to this discrepancy. To begin to test this theory, we examined pedal reaction forces and electromyography (EMG) of hindlimb muscles as a function of cycle phase and cadence in a rat model of MC. We found that higher cadences (≥30 RPM) increased EMG and force, with higher forces observed in animals with contusion injuries as compared with transections. To further investigate the forces, we developed a technique to separate rhythmic (developed with the motion of the pedals) from nonrhythmic forces. Rhythmic forces resulted from induced eccentric muscle contractions that increased (amplitude and prevalence) at higher cadences, whereas nonrhythmic forces showed the opposite pattern. Our results suggest that muscle activity during MC in rats depends on the stretch reflex, which, in turn, depends on the rate of muscle lengthening that is modulated by cadence. Additionally, we provide a framework for understanding MC that may help translate results from rat models to clinical use in the future.

Effect of Electrical Stimulation of the Vagus Nerve on Inflammation in Rats With Spinal Cord Injury

ObjectiveThe purpose of this study was to assess the effect of electroacupuncture stimulation (EAS) of the vagus nerve on the inflammatory response in rat models of spinal cord injury (SCI). MethodsThe T10 SCI model in adult male Sprague Dawley rats was established using the modified Allen's method. The EAS group was treated with the therapy on the vagus nerve of rat ear nails, while the SCI group did not receive any EAS treatment. The degree of inflammatory infiltration was reflected by hematoxylin-eosin staining. The inflammatory cytokines in spinal cord tissues, cerebrospinal fluid inflammation, and peripheral blood were detected by enzyme-linked immunosorbent assay. Changes in astrocytes and microglia were assessed using an immunofluorescence assay. ResultsElectroacupuncture stimulation treatment inhibited inflammatory infiltration, as well as the concentrations of interleukin-6, interleukin-1β, tumor necrosis factor-α, astrocytes, and microglia at 1, 6, and 24 hours after 1 EAS treatment. Multiple EAS treatments had an obvious effect on SCI inflammation. ConclusionA single EAS treatment had a limited effect on inflammation, but multiple treatments had a significant inhibitory effect on inflammation.

The Gelatin-Chitosan-Tetraethyl Orthosilicate Calcium Hydroxide Composite as a Potential Dental Pulp Medicament (Study on Expression of COX-2, PGP 9.5, TNF-α and Neutrophils number)

Introduction Calcium hydroxide (Ca(OH)2) is the material of choice for pulp therapy. However, Ca(OH)2 has drawbacks such as toxicity, poor sealing, and tunnel defect formation. Alternative materials have been developed to provide more biocompatible materials with better dentin formation ability. The objective of this study was to evaluate the effect of composites containing gelatin (G), chitosan (CH), tetraethyl orthosilicate (TEOS), and Ca(OH)2, namely G-CH-TEOS-Ca(OH)2 (Extended data) on inflammation of the dental pulp (expression of COX-2, PGP 9.5, TNF-α, and neutrophil number). Materials and methods A total of 16 Wistar rat models of acute pulp injury were prepared and divided into two groups, treatment and control, 8 with each. In the treatment group, we applied a pulp-capping material using G-CH-TEOS-Ca(OH)2 and Ca(OH)2. On the 1st and 3rd days, rats were sacrificed. Tissue samples from 4 rats in each group were processed for histological preparation. COX-2, PGP 9.5, and TNF-α were observed using immunohistochemical (IHC) staining, and neutrophil numbers were observed using hematoxylin-eosin staining. Image analysis of COX-2, PGP 9.5, and TNF-α expression was performed using ImageJ software. Results The results showed a decrease in COX-2 expression, but not significantly while PGP 9.5 and TNF-α expression were significantly higher than those in the control group. Neutrophil numbers were lower in the treatment group than in the control group, but the difference was not statistically significant. Conclusion The G-CH-TEOS-Ca(OH)2 composite material may have potential as an exposed pulp medicament by reducing inflammation (COX-2 expression and number of neutrophils) and increasing the regeneration factor (TNF-α expression) and nerve (PGP 9.5 expression).

The effects of therapeutic hypothermia on the expression of DKK3 and myocardial ischemia-reperfusion injury

BackgroundThe impact and mechanisms of therapeutic hypothermia (TH) on myocardial ischemia–reperfusion (I/R) injury are still unknown. MethodsSprague-Dawley (SD) rat model and primary cardiomyocytes were applied in our study. TTC staining evaluated myocardial infarction, while H&E staining assessed myocardial injury. ELISA quantified lactate dehydrogenase (LDH), IL-1β, IL-6, and TNF-α. Blood serum concentrations of CK, CK-MB, and cTnT were detected using a biochemical assay. TUNEL assay, flow cytometry and western blot were used to detect cell apoptosis. EdU assay was applied to examine cell proliferation. The expression of DKK3 and β-catenin protein was analyzed using Realtime PCR and Western blot. ResultsTH alleviated myocardial infarction size and injury in rat models of I/R, and reduced serum levels of myocardial injury markers and inflammatory factors in animal and cell models. In addition, TH inhibited the increased apoptosis and β-catenin expression as well as decreased DKK3 expression caused by I/R in I/R cell models, while si-DKK3 reversed the changes brought by TH, and XAV939 inhibited the effects of si-DKK3. ConclusionTH may reduce myocardial infarction size, myocardial injury, inflammatory response and apoptosis through DKK3/Wnt/β-catenin pathway, thereby alleviating myocardial I/R injury.

Sirt1/Nrf2/TNFα; TLR4/Myd88/NF-κB signaling pathways are involved in mediating hepatoprotective effect of bupropion in rat model of myocardial infarction

Background The aim of the current study is to identify the possible protective effect of bupropion (BUP) on liver injury in rat model of myocardial infarction (MI). BUP was administered in the presence and absence of MI. Materials and methods Thirty-two Wistar adult male rats were randomly arranged into four groups: control, BUP (30 mg/kg/day, intraperitoneal) for 28 days, isoproterenol (ISO) was injected subcutaneous (85 mg/kg) in the 26th and 27th days and BUP/ISO groups. Cardiac and hepatic enzymes were measured, also Hepatic oxidative stress indicators, as well as inflammatory and apoptotic biomarkers, were evaluated. Cardiac and hepatic histopathological examination and hepatic nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) immunohistochemical study were also detected. Results ISO significantly increased cardiac and hepatic enzymes, hepatic oxidative stress, inflammatory, apoptotic, with a histopathological picture of cardiac and hepatic damage and high hepatic NF-κB immunoexpression were detected. BUP significantly normalized the upraised oxidative, inflammatory, and apoptotic parameters, with an impressive improvement in the histopathological picture and a reduction in hepatic NF-κB immunoexpression. Conclusion BUP protects against liver injury on top of MI in rat model via modulation of Sirtuin type 1 (Sirt1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/tumor necrosis factor α (TNFα); Toll-like receptor 4 (TLR4)/Hepatic myeloid differentiation primary response 88(Myd88)/NF-κB signaling pathways.

The NCX1 calcium exchanger is implicated in delayed axotomy after peripheral nerve stretch injury.

After peripheral nerve stretch injury, most degenerating axons are thought to become disconnected at the time of injury, referred to as primary axotomy. The possibility of secondary axotomy-a delayed and potentially reversible form of disconnection-has not been evaluated. Here, we investigated secondary axotomy in a rat model of sciatic nerve stretch injury. We also evaluated whether axon sparing and functional improvement results from pharmacological blockade of the sodium-calcium exchanger 1 (NCX1), which is widely believed to contribute to traumatic axon degeneration but was previously only investigated in vitro. We studied peripheral nerve secondary axotomy in a clinically relevant rat model of sciatic nerve rapid stretch injury with immunolabeling and fluorescence microscopy. The role of NCX1 in secondary axotomy was studied with pharmacological inhibition with SEA0400 and immunolabeling, immunoblot, and behavioral assays. We found that early after injury, many axons remained in-continuity and that degeneration of axons was delayed, consistent with the occurrence of secondary axotomy. βAPP, a marker of secondary axotomy, accumulated at regions of axon swelling and disconnection, and NCX1 was upregulated and co-localized to βAPP axonal swellings. Pharmacological blockade of NCX1 after injury reduced calpain activation, proteolytic degradation of neurofilaments, βAPP accumulation, distal axon degeneration, and improved hindlimb function. Our data demonstrate a major role for secondary axotomy in peripheral nerve stretch injury and identify NCX1 as a promising therapeutic target to reduce secondary axotomy and improve functional outcome after nerve injury.

Therapeutic effects of fecal microbial transplantation on alcoholic liver injury in rat models

ObjectiveDisruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques. MethodsThree liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats. ResultsFMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways. ConclusionFMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.

Magnetic resonance imaging classification in a percutaneous needle injury rat model of intervertebral disc degeneration

BackgroundDuring the development of disease-modifying intervertebral disc degeneration (IDD) drugs, the rat model of IDD is frequently used for disease progression assessment. The aim of this study was to describe a magnetic resonance (MRI) scoring system for the assessment of different disc conditions in puncture-induced IDD, allowing standardization and comparison of results obtained by different investigators.MethodsA total of 36 Sprague-Dawley rats were utilized in the present study. The animals were divided into two groups: a sham group and an IDD group caused by puncture. The rats in the IDD group were subsequently divided into six categories based on time frames, with five rats in each category. The sham group was divided into two sub-groups (n = 3) for 28 and 56 days, respectively. T2-weighted images of rats consecutively studied with MRI of the coccygeal discs were classified according to the time course using the corresponding histological data. Additional scoring of the micro-CT was employed to identify the progression of bone destruction of the rat model of IDD.ResultsA comparison of the MRI results between the sham group and the IDD group revealed a significant reduction in NP height, area, T2WI value, and DHI in the latter group (P < 0.05). The micro-CT results demonstrated that following acupuncture, there was a notable decline in the BV, Tb.N, and height of the coccygeal vertebra, while the BS/BV and Tb.Sp exhibited a significant increase (P < 0.05). The histological results were analogous to the MRI results, indicating a progressive exacerbation of IDD and a corresponding increase in NP score (P < 0.05). The results of the MRI were found to be consistent with those of the micro-CT and histological analyses (P < 0.05). The results of the study demonstrate a robust correlation between MRI analysis and histological findings. Live animals are employed for MRI analysis to improve experiment comparability. The reliability of the MRI scoring system ensures assessment of disease progression in live animals, while promoting cost savings and animal welfare by avoiding the sacrifice of animals at different times.ConclusionsThe described scoring paradigm has quantitatively been found to differentiate IDD disease progression in an in vivo rat model. Hence, we suggest employing it to evaluate the rat IDD model and assess the effects of treatments in this model.

Sodium Hydrosulfide Protects Rats from Hypobaric-Hypoxia-Induced Acute Lung Injury

Hydrogen sulfide (H2S), as a key gas signaling molecule, plays an important role in regulating various diseases, with appropriate concentrations providing antioxidative, anti-inflammatory, and anti-apoptotic effects. The specific role of H2S in acute hypoxic injury remains to be clarified. This study focuses on the H2S donor sodium hydrosulfide (NaHS) and explores its protective effects and mechanisms against acute hypoxic lung injury. First, various mouse hypoxia models were established to evaluate H2S’s protection in hypoxia tolerance. Next, a rat model of acute lung injury (ALI) induced by hypoxia at 6500 m above sea level for 72 h was created to assess H2S’s protective effects and mechanisms. Evaluation metrics included blood gas analysis, blood routine indicators, lung water content, and lung tissue pathology. Additionally, LC-MS/MS and bioinformatic analyses were combined in performing quantitative proteomics on lung tissues from the normoxic control group, the hypoxia model group, and the hypoxia model group with NaHS treatment to preliminarily explore the protective mechanisms of H2S. Further, enzyme-linked immunosorbent assays (ELISA) were used to measure oxidative stress markers and inflammatory factors in rat lung tissues. Lastly, Western blot analysis was performed to detect Nrf2, HO-1, P-NF-κB, NF-κB, HIF-1α, Bcl-2, and Bax proteins in lung tissues. Results showed that H2S exhibited significant anti-hypoxic effects in various hypoxia models, effectively modulating blood gas and blood routine indicators in ALI rats, reducing pulmonary edema, improving lung tissue pathology, and alleviating oxidative stress, inflammatory responses, and apoptosis levels.

N-Terminal Capping of the αO-Conotoxin Analogue GeX-2 Improves the Serum Stability and Selectivity toward the Human α9α10 Nicotinic Acetylcholine Receptor.

α9α10 nicotinic acetylcholine receptors (nAChRs) are a promising nonopioid analgesic target, with α9α10 nAChR antagonists showing efficacy against chemotherapy-induced hyperalgesia and allodynia. GeX-2, a potent analgesic conotoxin antagonist of α9α10 nAChRs, has limited serum stability. This study improved GeX-2 stability by capping its N-terminal with fatty acids or polyethylene glycol chains, which enhanced its serum stability but eliminated activity at G protein-coupled γ-aminobutyric acid type B (GABAB) receptor-coupled CaV2.2 channels while preserving activity at α9α10 nAChRs. In vivo, α9α10 nAChRs antagonism alone did not alleviate neuropathic pain, highlighting the importance of GABAB receptor-coupled CaV2.2 channels in GeX-2's antinociceptive effects in the chronic constriction injury rat model. The GeX-2 analogue, with an N-terminal methyl group, showed improved activity and selectivity for α9α10 nAChRs, increased serum half-life, and strong analgesic effects in oxaliplatin-induced cold allodynia models. AlphaFold3 and molecular dynamics simulations provided insights into the binding modes and the effects of N-terminal capping, which informed future peptide therapeutic developments.

Comparative Effects of Fedratinib and Upadacitinib on Renal Ischemia-Reperfusion Injury in Rat Models

Renal ischemia-reperfusion injury (RIRI) is a severe condition that frequently occurs following kidney transplantation or surgical procedures affecting renal blood flow. Inflammatory responses, oxidative stress, and apoptotic pathways significantly contribute to RIRI. This study aimed to compare the renoprotective effects of Fedratinib, a JAK2 inhibitor, and Upadacitinib, a JAK1 inhibitor, in rat models of RIRI. Both inhibitors were administered one hour prior to ischemia induction, and the effects on renal function, inflammation, and cell death pathways were assessed. The findings revealed that both Fedratinib and Upadacitinib significantly reduced serum creatinine and urea levels, inflammatory cytokines (TNF-α, IL-6), and markers of apoptosis (BCL2/BAX) by suppressing the JAK/STAT signaling pathways. Histopathological analysis showed substantial reduction in renal tissue damage in the treated groups compared to controls. The study concludes that JAK inhibition by either drug provides significant renoprotection in RIRI, though with some differences in the degree of pathway inhibition and clinical implications.

Taming hemoglobin chemistry-a new hemoglobin-based oxygen carrier engineered with both decreased rates of nitric oxide scavenging and lipid oxidation.

The clinical utility of hemoglobin-based oxygen carriers (HBOC) is limited by adverse heme oxidative chemistry. A variety of tyrosine residues were inserted on the surface of the γ subunit of recombinant fetal hemoglobin to create novel electron transport pathways. This enhanced the ability of the physiological antioxidant ascorbate to reduce ferryl heme and decrease lipid peroxidation. The γL96Y mutation presented the best profile of oxidative protection unaccompanied by loss of protein stability and function. N-terminal deletions were constructed to facilitate the production of recombinant hemoglobin by fermentation and phenylalanine insertions in the heme pocket to decrease the rate of NO dioxygenation. The resultant mutant (αV1del. αL29F, γG1del. γV67F, γL96Y) significantly decreased NO scavenging and lipid peroxidation in vitro. Unlike native hemoglobin or a recombinant control (αV1del, γG1del), this mutation showed no increase in blood pressure immediately following infusion in a rat model of reperfusion injury, suggesting that it was also able to prevent NO scavenging in vivo. Infusion of the mutant also resulted in no meaningful adverse physiological effects apart from diuresis, and no increase in oxidative stress, as measured by urinary isoprostane levels. Following PEGylation via the Euro-PEG-Hb method to increase vascular retention, this novel protein construct was compared with saline in a severe rat reperfusion injury model (45% blood volume removal for 90 minutes followed by reinfusion to twice the volume of shed blood). Blood pressure and survival were followed for 4 h post-reperfusion. While there was no difference in blood pressure, the PEGylated Hb mutant significantly increased survival.

128 - The effects of a novel photo-reactive NO-donor “NORD-1” on internal urethral relaxation using an intrapelvic nerve injury rat model.

128 - The effects of a novel photo-reactive NO-donor “NORD-1” on internal urethral relaxation using an intrapelvic nerve injury rat model.

Definition of Synovial Mesenchymal Stem Cells for Meniscus Regeneration by the Mechanism of Action and General Amp1200 Gene Expression.

The quality control (QC) of pharmaceutical-grade cell-therapy products, such as mesenchymal stem cells (MSCs), is challenging. Attempts to develop such products have been hampered by difficulties defining cell-type-specific characteristics and therapeutic mechanisms of action (MoAs). Although we have developed a cell therapy product, FF-31501, consisting of human synovial MSCs (SyMSCs), it was difficult to find specific markers for SyMSCs and to define the cells separately from other MSCs. The purpose of this study was to create a method for identifying and defining SyMSCs from other tissue-derived MSCs and to delve deeper into the mechanism of action of SyMSC-induced meniscus regeneration. Specifically, as a cell-type-dependent approach, we constructed a set of 1143 genes (Amp1200) reported to be associated with MSCs and established a method to evaluate them by correlating gene expression patterns. As a result, it was possible to define SyMSCs separately from other tissue-derived MSCs and non-MSCs. In addition, the gene expression analysis also highlighted TNSF-15. The in vivo rat model of meniscus injury found TNSF-15 to be an essential molecule for meniscus regeneration via SyMSC administration. This molecule and previously reported MoA molecules allowed an MoA-dependent approach to define the mechanism of action for SyMSCs. Therefore, SyMSCs for meniscus regeneration were defined by means of two approaches: the method to separate them from other MSCs and the identification of the MoA molecules. These approaches would be useful for the QC of cell therapy products.

Resveratrol and Exercise Produce Recovered Ankle and Metatarsus Joint Movements after Penetrating Lesion in Hippocampus in Male Rats.

Introduction: This study investigates how traumatic injuries alter joint movements in the ankle and foot. We used a brain injury model in rats, focusing on the hippocampus between the CA1 and dentate gyrus. Materials and Methods: We assessed the dissimilarity factor (DF) and vertical displacement (VD) of the ankle and metatarsus joints before and after the hippocampal lesion. We analyzed joint movements in rats after the injury or in rats treated with resveratrol, exercise, or a combination of both. Results: Resveratrol facilitated the recovery of DF in both legs, showing improvements in the ankle and metatarsus joints on the third and seventh days post-injury. The hippocampal lesion affected VD in both legs, observed on the third or seventh day after the injury. Both exercise and resveratrol partially recovered VD in the ankle and metatarsus joints on these days. These effects may be linked to increased hippocampal neurogenesis and reduced neuroinflammation. Conclusions: The study highlights the benefits of resveratrol and exercise in motor recovery following brain injury, suggesting their potential to enhance the quality of life for patients with neurological disorders affecting motor function and locomotion. These findings also suggest that resveratrol could offer a promising or complementary alternative in managing chronic pain and inflammation associated with orthopedic conditions, thus improving overall patient management.

Electroacupuncture alleviates sciatic nerve injury and inhibits autophagy in rats.

Sciatic nerve injury is a common form of peripheral nerve injury (PNI). It has been suggested that electroacupuncture (EA) stimulation at GB30 and ST36 can improve nerve dysfunction post-PNI. Autophagy is an important factor in the regeneration of sciatic nerves and recovery of motor function. Therefore, we investigated the biological effects of EA and examined whether these were mediated by autophagy in sciatic nerve injury. Mechanical clamping of the sciatic nerve in Sprague-Dawley rats was performed to establish an experimental model of sciatic nerve injury. EA stimulation was administered once daily for 15 min for seven consecutive days beginning 1 week after successful modeling. The recovery of sciatic nerve function was examined via the sciatic functional index (SFI) test. Morphometric analysis was conducted by staining nerve samples with toluidine blue. Autophagy-associated protein levels were measured via Western blotting. EA stimulation at GB30 and ST36 significantly increased the number of myelinated fibers, axonal and fiber diameters, and the thickness of the myelin sheath in our rat model of sciatic nerve injury. In addition, EA stimulation greatly facilitated nerve regeneration following sciatic nerve injury. Moreover, sciatic nerve injury-induced autophagy was inhibited by EA stimulation. EA facilitates recovery of injured sciatic nerves and inhibits autophagy in a rat model.

Artichoke leaf hydroethanolic extract reduces neuropathic pain in a rat model of chronic constriction injury via attenuating the sciatic nerve oxidative stress

Neuropathic pain, a nerve damage consequence, presents symptoms such as dysesthesia, hyperalgesia, and allodynia. This study aimed to evaluate the alleviating potential of artichoke leaf extract in neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in male rats. The hydroethanolic extract of artichoke leaf was administered via gavage at doses of 200, 400, and 800 mg/kg for 21 days. Behavioural tests were conducted on days 1, 4, 7, 14, and 21 post-surgeries. Only the dose of 800 mg/kg significantly reduced thermal hyperalgesia and allodynia from day 14 and mechanical allodynia from day 7, and the other doses did not affect behaviours. Biochemical analysis showed that artichoke extract decreased lipid peroxidation and restored antioxidant enzyme activities (SOD and GPx) in the sciatic nerve tissue. In conclusion, artichoke leaf extract administration diminishes neuropathic pain-related behaviours by enhancing antioxidant capacity and reducing oxidative stress in the rats’ sciatic nerve.

Comment on, "Hypoxia preconditioning protects neuronal cells against traumatic brain injury through stimulation of glucose transport mediated by HIF-1α/GLUTs signaling pathway in rat".

Wu et al. (2021) investigated the neuroprotective effects of hypoxia preconditioning (HPC) in a rat model of traumatic brain injury (TBI). The study demonstrated that HPC enhances brain resilience to TBI by upregulating glucose transporters GLUT1 and GLUT3 through the HIF-1α signaling pathway. Comprehensive molecular and histological analyses confirmed increased expression of these transporters, correlating with reduced neuronal apoptosis and cerebral edema. The robust methodology, including rigorous statistical validation and time-course assessments, underscores HPC's potential therapeutic role in mitigating neuronal loss and improving glucose transport post-injury. However, the study could be strengthened by incorporating additional preconditioning controls, comparative analyses with other neuroprotective strategies, and exploring downstream metabolic effects in greater detail. Furthermore, expanding the research to include diverse animal models and examining sex-dependent responses would enhance the generalizability and translational relevance of the findings. Future studies should also integrate metabolic flux analysis and advanced imaging techniques to further elucidate HPC's mechanisms of action.

Prophylactic and Therapeutic Effects of Progesterone on the Preterm Brain Injury Rat Model.

Neurodevelopmental disorders are chronic conditions affecting behavior, cognition, and social function, often arising from early brain development disruptions. Preterm infants are particularly vulnerable to brain injuries, such as periventricular leukomalacia, which can lead to long-term disabilities. This study aimed to investigate the neuroprotective effect of progesterone in reducing the severity of a preterm brain injury in rat model. A preterm brain injury rat model was established using lipopolysaccharide to induce brain injury. The neuroprotective effects of progesterone were evaluated through histological assessments comparing treated and untreated groups. The study also aimed to assess the efficacy of progesterone in controlling brain injury severity. The findings suggest that progesterone exhibits neuroprotective properties, with a significant difference in the severity of brain injury. The histological evaluations suggest that progesterone may reduce inflammation and promote neuronal survival in preterm brain injury. The administration of progesterone shows promising results as a therapeutic strategy for preventing and treating brain injuries in preterm rat pups. Further research is needed to explore the underlying mechanisms and potential clinical applications of the hormone.