Sham Group Research Articles

The Efficacy of Intrathecal Platelet-Rich Plasma Administration in Alleviation of Chronic Neuropathic Pain in Rat Model.

Chronic neuropathic pain (CNP), marked by various stinging sensations, frequently arises from lumbosacral disorders, where astrocytes in the spinal dorsal horn (SDH) significantly contribute to its persistence. Platelet-rich plasma (PRP) treatment has shown regulatory effects on astrocytic activity in inflammatory and diabetic neuropathy, yet its impact on CNP remains unclear. This study investigates the potential of intrathecal PRP injections for mitigating CNP in a chronic compressed dorsal root ganglion (CCD) rat model. Animals were divided into CCD, sham, and control groups. PRP or phosphate-buffered saline (PBS) was injected intrathecally between the L4-L5 spinal cord. Assessments included mechanical and thermal pain behavioral tests, and in vivo extracellular recordings from the contralateral ventral posterolateral (VPL) thalamus. Additionally, the expression of astrocytic pain mediators in the SDH was analyzed through immunofluorescence. Results showed that the CCD group had significantly lower pain thresholds compared to the sham group. PRP treatment led to improved CNP responses in CCD rats, unlike in the PBS group, highlighting PRP's role in CNP amelioration. Electrophysiology confirmed a notable reduction in VPL thalamic activity post-PRP treatment. Immunofluorescence (IFC) analysis revealed significant increases in neuronal c-fos expression in the DRG and SDH of CCD rats, which were notably reduced following PRP treatment. IFC analysis also indicated decreased expression of pain-transmission-associated astrocyte markers, including glial fibrillary acidic protein (GFAP), pyruvate kinase M2 (PKM2), and high mobility group box-1 protein (HMGB1) in PRP-treated CCD subjects. Thus, we demonstrate that PRP attenuates CNP in a CCD rat model by regulating nociceptive input into the spinothalamic tract through the inhibition of astrocytic activity in SDH, presenting itself as a viable therapy for CNP linked to lumbosacral conditions.

Preliminary investigation on the correlation between karyopherin alpha 4 and acute cerebral infarction

Objective: Acute cerebral infarction (ACI) has a high incidence and complex etiology, so searching for specific diagnosis and therapeutic target molecules is highly important. This paper aimed to explore the mechanism of karyopherin alpha 4 (KPNA4) in ACI. Material and Methods: Four groups were established: sham group, middle cerebral artery occlusion (MCAO) group, MCAO + small interfering negative control (si-NC group), and MCAO + si-KPNA4 group. The Zea-Longa scoring standard was adopted to assess the neurological impairment of ACI rats. The expression of KPNA4 was verified by real-time quantity polymerase chain reaction assay and Western blot. 2,3,5-Triphenyltetrazolium chloride and hematoxylin and eosin staining were used to examine the effects of KPNA4 knockdown on brain injury in ACI rats. The apoptosis of oxygen-glucose deprivation (OGD)-SH-SY5Y cells was measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Western blot analysis was performed to analyze the expression levels of apoptosis-related proteins, inflammatory factors, and nuclear factor kappa B (NF-κB) pathway-related proteins. Results: KPNA4 was overexpressed in the MCAO rat brain (P < 0.0001) and OGD-SH-SY5Y cells (P < 0.0001). Knocking down KPNA4 significantly reduced the degree of brain damage (P < 0.0001) and reduced the apoptosis of OGD-SH-SY5Y cells (P < 0.001). KPNA4 knockdown also significantly decreased the expression levels of inflammatory factors (interleukin [IL]-1β, tumor necrosis factor-α, and IL-18; P < 0.0001) and prohibited the phosphorylation of the inhibitor of NF-κB and p65 (P < 0.0001). However, NF-κB agonist lipopolysaccharide reversed the inhibition of KPNA4 knockdown. Conclusion: In general, KPNA4 knockdown can mitigate ACI-induced damage by regulating the NF-kB pathway. This finding provides a new perspective on the treatment of ACI.

Assessing the effectiveness of multi-session online emotion recognition training in autistic adults.

Difficulties with emotion recognition can occur in neurodevelopmental conditions, including in autistic individuals. Providing interventions to support this would therefore be beneficial, particularly in terms of downstream effects on wellbeing, social relationships and education. In this online experimental study, we examined the effect of a recently developed facial emotion recognition training task versus a sham/control task in an adult population who self-identified as autistic over four sessions in a 2-week period, with a fifth follow-up session (N = 184). Our main analyses showed that facial emotion recognition accuracy was greater in Session 4 in the active group, with an estimated improvement of 14% (equivalent to approximately 7 additional correct responses), compared to 2% (equivalent to approximately 1 additional correct responses) in the sham group (p = 4x10-09). Additional analyses suggested training effects were generalisable to facial stimuli that participants had not been trained on and were still present, although attenuated, two weeks later. We also observed some self-reported improvements in social interactions post-training. Overall, this study demonstrated improved emotion recognition with this training task in an adult sample who self-identified as autistic. Future work is needed to investigate the effect of this task on emotion recognition accuracy in those with a formal diagnosis of autism, and in autistic children where support could be most beneficial.

Changes in gene expression of D2 and D5 receptors in the thalamus and midbrain caused by a persistent painful stimulus in Parkinsonian rats.

Changes in gene expression of D2 and D5 receptors in the thalamus and midbrain caused by a persistent painful stimulus in Parkinsonian rats.

Roux-en-Y gastric bypass improves liver and glucose homeostasis in Zucker diabetic fatty rats by upregulating hepatic trefoil factor family 3 and activating the phosphatidylinositol 3-kinase/protein kinase B pathway.

Roux-en-Y gastric bypass improves liver and glucose homeostasis in Zucker diabetic fatty rats by upregulating hepatic trefoil factor family 3 and activating the phosphatidylinositol 3-kinase/protein kinase B pathway.

Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Increase in endothelial microparticles is negatively correlated with decrease in renal microperfusion in septic rats.

Increase in endothelial microparticles is negatively correlated with decrease in renal microperfusion in septic rats.

An experimental study on the optimal timing of modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats.

An experimental study on the optimal timing of modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats.

Modulation of dopaminergic transmission and brain activity by frontotemporal tDCS: A multimodal PET-MR imaging study.

Transcranial Direct Current Stimulation (tDCS) is a promising noninvasive intervention for schizophrenia, particularly when applied using a frontotemporal montage. Although significant clinical benefits have been reported, the variability in individual responses underscores the need for a more comprehensive understanding of its underlying neurophysiological mechanisms. Here, we used a simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) approach (PET-MR) to investigate the effects of frontotemporal tDCS on dopamine transmission, cerebral perfusion, and white matter microstructural integrity in healthy individuals. In a double-blind, two-arm, parallel group study, 30 healthy volunteers were randomly allocated to receive a single session of either active (n=15) or sham (n=15) frontotemporal tDCS. The stimulation session was delivered during simultaneous multimodal PET-MR imaging, which combined PET with the [11C]raclopride radiotracer, Arterial Spin Labeling (ASL), and Diffusion Weighted Imaging. PET [11C]raclopride analysis revealed a significant reduction in Non-Displaceable Binding Potential in the left executive striatal subregion 15min after tDCS in the active group, compared to both baseline and the sham group. This finding suggests that frontotemporal tDCS may induce an increase in dopamine release. ASL analysis showed that active tDCS may reduce cerebral blood flow in the precuneus compared to sham stimulation. No significant effects of tDCS were observed on white matter microstructural integrity. This study provides new insights into the neurophysiological mechanisms of frontotemporal tDCS, paving the way for the optimization of therapeutic strategies for patients with dysregulated cortico-subcortical dopamine systems.

Pro-histaminergic drug restores balance, promotes microgliogenesis and modulates neuroinflammation after vestibular injury.

Pro-histaminergic drug restores balance, promotes microgliogenesis and modulates neuroinflammation after vestibular injury.

Radiation Quality-Dependent Progressive Increase in Oxidative DNA Damage and Intestinal Tumorigenesis in Apc1638N/+ Mice

Exposure to high-linear energy transfer (LET) heavy ions, such as 28Si, poses a significant cancer risk for astronauts. While previous studies have linked high-LET radiation exposure to persistent oxidative stress and dysregulated stress responses in intestinal crypt cells with an increased risk of tumorigenesis, the relationship between IR-induced oxidative DNA damage and intestinal cancer risk remains incompletely understood. Here, we investigated the time-dependent effects of 28Si-ion radiation on intestinal tumorigenesis and oxidative DNA damage in Apc1638N/+ mice, a model for human intestinal cancer predisposition. Male Apc1638N/+ mice were exposed to 10 cGy of either γ-rays (low-LET) or 28Si-ions (high-LET), and intestinal tumor burden was assessed at 60 and 150 days post-irradiation. While both radiation groups showed modest, non-significant tumor increases at 60 days, 28Si-irradiated mice exhibited an approximately 2.5-fold increase in tumor incidence by 150 days, with a higher incidence of invasive carcinomas compared to γ and sham groups. Serum 8-OxodG levels, a marker of systemic oxidative stress, were significantly elevated in the 28Si-ion group, correlating with increased intestinal 8-OxodG staining. Additionally, assessment of the proliferation marker Cyclin D1 and metaplasia marker Guanylyl Cyclase C (GUCY2C) also revealed significant crypt cell hyperproliferation accompanied by increased metaplasia in 28Si-exposed mouse intestines. Positive correlations between serum 8-OxodG and tumor-associated endpoints provide compelling evidence that exposure to 28Si-ions induces progressive intestinal tumorigenesis through sustained oxidative DNA damage, crypt cell hyperproliferation, and metaplastic transformation. This study provides evidence in support of the radiation quality-dependent progressive increase in systemic and intestinal levels of 8-OxodG during intestinal carcinogenesis. Moreover, the progressive increase in oxidative DNA damage and simultaneous increase in oncogenic events after 28Si exposure also suggest that non-targeted effects might be a significant player in space radiation-induced intestinal cancer development. The correlation between serum 8-OxodG and oncogenic endpoints supports its potential utility as a predictive biomarker of high-LET IR-induced intestinal carcinogenesis, with implications for astronaut health risk monitoring during long-duration space missions.

Liyan Kaiyin Formula relieves reflux pharyngitis by regulating M1 macrophage polarization via the NF-κB/NLRP3 pathway.

Liyan Kaiyin Formula relieves reflux pharyngitis by regulating M1 macrophage polarization via the NF-κB/NLRP3 pathway.

Cl-amidine confers organ protection and improves survival in hemorrhagic shock rats via the PAD4-CitH3-NETs axis.

The occurrence of multi-organ dysfunction following hemorrhagic shock (HS) remains a critical clinical challenge. The excessive formation of neutrophil extracellular trap (NET) Has been identified as a pivotal pathogenic mechanism. This study preliminarily elucidated the protective mechanism of the PAD4 inhibitor Cl-amidine in a rat model of HS. Male Sprague-Dawley rats were subjected to sublethal (40% blood loss, n = 8) or lethal (50% blood loss, n = 10) HS. Rats were divided into Sham group (catheter placement only), HS group (catheter placement followed by blood withdrawal), Vehicle group (0.9% saline), and Cl-amidine (10 mg/kg in 0.9% saline) groups. Cl-amidine significantly improved the 72-h survival rate and delayed mortality in lethal HS. In Sublethal HS, the drug corrected metabolic disturbances, such as reduced lactate accumulation, while maintaining mean arterial pressure. Mechanistically, the effects of Cl-amidine included reducing circulating cell-free DNA (cf-DNA) and tissue citrullinated histone H3 (CitH3) levels, suppressing PAD4 expression, and improving histopathological outcomes (reduced edema and restored intestinal barrier integrity by upregulation of tight junction proteins Claudin-1/ZO-1). Moreover, Cl-amidine inhibited neutrophil infiltration through ICAM-1 downregulation and reduced the production of TNF-α and IL-6. In conclusion, Cl-amidine protects against HS by targeting the PAD4-CitH3-NETs axis, breaking the vicious cycle of "NETs-inflammation", restoring barrier integrity, and alleviating multi-organ damage. The synergistic downregulation of ICAM-1 further enhances the therapeutic efficacy, highlighting Cl-amidine as a novel NETs-modulating strategy for HS. This study provides a theoretical and therapeutic foundation for the prevention and treatment of multi-organ injury following HS.

Presence of dysfunctional soluble guanylate cyclase in mesenteric resistance arteries from rats with mild ligature-induced periodontitis.

Presence of dysfunctional soluble guanylate cyclase in mesenteric resistance arteries from rats with mild ligature-induced periodontitis.

Fibroblast to macrophage-like cell transition in renal inflammatory injury through the MR/CSF1 pathway induced by aldosterone.

Fibroblast to macrophage-like cell transition in renal inflammatory injury through the MR/CSF1 pathway induced by aldosterone.

A Combat-Relevant Model of Traumatic Hemorrhage in Rats for the Study of Combined Radiation Injury: A Pilot Study.

The threat and consequences of nuclear or radiological events remain a military concern today. It is estimated that 65-70% of weapon-related injuries after a nuclear event will be radiation combined injuries, i. e., acute radiation injury along with hemorrhage and traumatic injuries such as blast or other burns, bone fractures, soft tissue injuries, blood loss, and/or hypoxia. However, little is known about most types of traumatic injuries associated with blood loss, as might occur during combat operations. The primary objective of this pilot study was to develop a new animal model that incorporates both hemorrhage and traumatic injury, combined with radiation exposure. Male Sprague-Dawley rats were divided into four groups (6/group): 1. sham; 2. radiation injury (RI); 3. traumatic hemorrhage (TH), which is hemorrhage combined with extremity trauma; and 4. RI+TH. Radiation injury consisted of a single X-ray dose of 5. 5.5 Gy delivered at a rate of 1 Gy/min. Hemorrhage involved a stepwise reduction of 37% of the estimated blood volume. Extremity trauma consisted of fibular fractures and penetrating and soft tissue injuries to a single extremity. Heart rate, mean arterial blood pressure (MAP), and blood indices were analyzed at intervals corresponding to pre-hemorrhage, end of hemorrhage, and 4 h after hemorrhage, with survival observed for 14 days. Radiation injury alone had little impact on the measured variables. Hemorrhage resulted in a 60% and 67% reduction in MAP in the traumatic hemorrhage and RI+TH groups, respectively, immediately after hemorrhage, which recovered by 4 h in the traumatic hemorrhage group but not in RI+TH group. A similar pattern was observed for blood lactate levels. Traumatic hemorrhage and radiation injury resulted in 50% mortality, although mortality occurred earlier after traumatic hemorrhage. RI+TH produced 80% mortality by day 4. No mortality was observed in the sham group. By combining a high dose of X-ray radiation with our established model of traumatic hemorrhage, we have developed a new rodent model that mimics combat casualties during nuclear or radiological events.

The Effect of Resistance Training and Androgen Administration on Neuromuscular Junction Morphology and Neurotrophin Expression.

This study examined the effect of resistance training (RT) and nandrolone decanoate (ND) administration on neuromuscular junction (NMJ) morphology and neurotrophin expression. Forty 3-month-old male C57Bl/6 J mice were randomized to a RT or sedentary (SED) group. Each group of animals were further divided into sham (S) or ND (35 mg/kg/week) groups. All interventions were seven weeks in duration. Brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), p75 and androgen receptor expression (AR) in the plantaris and soleus muscles were examined via western blot, while NMJ morphology was examined via immunofluorescence. Significant interactions for BDNF expression was noted in the plantaris (p = 0.009) and soleus (p = 0.010). In the plantaris BDNF expression for RT-ND was greater than RT-S (p = 0.019) and SED-ND (p = 0.016), while BDNF expression in RT-S was greater than all other groups (p's < 0.05) in the soleus. A significant interaction for TrkB expression was observed in the plantaris. TrkB in RT-ND was significantly greater (p = 0.031) than SED-ND. Analysis of the postsynaptic membrane within the plantaris revealed that RT increased the acetylcholine (ACh) receptor-stained area (p = 0.036), ACh-stained perimeter (p = 0.006), and total area (p = 0.044) compared to SED. In addition, ND administration increased (p = 0.050) ACh total area. In the presynaptic membrane both RT and ND increased ACh vesicle-stained area (p < 0.001 and p = 0.006, respectively), ACh vesicle-stained perimeter (p < 0.001 and p = 0.02, respectively), and ACh vesicle total area (p < 0.001 and p = 0.01, respectively), while RT only was noted to increase presynaptic ACh vesicles total perimeter (p < 0.001). In the soleus, ND increased ACh receptor-stained (p = 0.002) and total area (p = 0.035) at the post-synaptic membrane. RT and ND administration stimulate increases in neurotrophin expression and NMJ morphology in plantaris and soleus muscles.

Detecting DWI-Negative Strokes in Rat Models of Acute Internal Carotid Artery Occlusion using Magnetic Resonance Spectroscopy.

To explore the potential of Magnetic Resonance Spectroscopy (MRS) for the early diagnosis of the ischemic brain tissue with negative Diffusion Weighted Imaging (DWI) results in the model of acute internal carotid artery occlusion (AICAO) in rats. Fifteen rats were randomly assigned to three groups: the sham group (SHAM, n=5), the 2-hour ischemia model group (CI2H, n=5), and the 12-hour ischemia model group (CI12H, n=5). In the experimental group, the method of acute internal carotid artery occlusion was adopted to establish a right cerebral ischemia model. After the successful establishment of the model, DWI and MRS scans were first performed, and then the MRS results were recorded. Immunohistochemical analysis of zonula occludens-1 (ZO-1), neuron-specific enolase (NSE), S-100β protein, and cytochrome C (CytC) was conducted on paraffin-embedded brain sections, followed by Spearman correlation analysis between relevant parameters and these proteins. Lipid (Lip) levels were lower in the SHAM group compared to the CI2H group (P<0.05), but no significant difference was observed between the SHAM and CI12H groups. Lip was negatively correlated with ZO-1 across all groups (ρ=-0.768, P<0.001). Lactate (Lac) levels were lower in the SHAM group than in the CI2H and CI12H groups (P<0.05), and Lac was positively correlated with CytC across all groups (ρ=0.801, P<0.001). Apparent Diffusion Coefficient (ADC) values on the right side of the brain were lower in the CI12H group than in the SHAM group (P<0.05), with no significant difference compared to the CI2H group.The level of N-acetyl aspartate (NAA) in the CI12H group was lower than that in the SHAM group and the CI2H group (P < 0.05), and there was no statistically significant difference in the level of NAA between the CI2H group and the SHAM group. The Cho level in the CI12H group exhibited a statistically significant increase compared to both the SHAM and CI2H groups (P < 0.05), and there was no statistically significant difference in the level of Choline (Cho) between the CI2H group and the SHAM group. Brain damage in AICAO rats became evident at two hours after successful modeling. MRS detected brain damage earlier than DWI, with Lac and Lip as the most sensitive markers, preceding changes in NAA, Cho, and ADC values.

Comparative effects of 10-Hz rTMS and iTBS on cortico-striatal connectivity in major depressive disorder: a sham-controlled study.

Abnormalities in the prefrontal cortex (PFC)-related network play an important role in the pathophysiology of major depressive disorder (MDD). Accumulating evidence indicated that fronto-striatal dysconnectivity is critical to MDD pathogenesis. Whether non-invasive brain stimulation, including 10-Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS), may change cortico-striatal functional connectivity (FC) in MDD patients is unclear. Whether the change of cortico-striatal FC is associated with the antidepressant effects is also unknown. In total, 68 adult MDD subjects were randomly assigned to one of three groups: iTBS, 10-Hz rTMS, or sham group. Functional connectivity was analyzed using MRI and seed-based methods. Seeds included left and right dorsal caudate (DC), dorsal rostral putamen (DRP), and ventral rostral putamen (VRP). The results revealed that significant group-by-time interactions in FC were found in all the striatal seeds. Post-hoc analyses revealed significant increases in FC of the left DRP and VRP for both iTBS and rTMS treatments, particularly with the right frontal pole. Greater FC changes of the fronto-striatal networks correlated with the antidepressant effects. The effects of rTMS and iTBS on FCs of the intra-striatal network, default mode network, and other cortico-striatal networks were distinct. In conclusion, the first study demonstrated that iTBS and rTMS had common but unique effects on the cortico-striatal and intra-striatal networks. These results suggest that both treatments regulate brain reward systems and might be used to treat various striatum-related neuropsychiatric illnesses.

Penehyclidine Hydrochloride Improves Ischemia-Reperfusion Injury in Lung Transplantation by Inhibiting Inflammatory Response and Oxidative Stress Injury.

Penehyclidine Hydrochloride Improves Ischemia-Reperfusion Injury in Lung Transplantation by Inhibiting Inflammatory Response and Oxidative Stress Injury.