a-modified-method-for-intrathecal-catheterization-in-rats

A Modified Method for Intrathecal Catheterization in Rats

Intrathecal catheterization has been widely applied in animal experiments, especially those on neuropathic pain. However, the traditional methods still ...

Naval Medical University

: The protective effects of 2%-4% hydrogen gas in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) have been previously reported. This study aimed to assess the neuroprotective effects of high concentration hydrogen (HCH) on DEACMP.: A total of 36 male Sprague-Dawley rats were divided into 3 groups. In the DEACMP group, rats were exposed to CO to induce CO poisoning; in the HCH group, the animals were exposed to 67% H and 33% O at 3,000 mL/min for 90 min immediately after CO poisoning. Neurological function was evaluated at 1 and 9 days after poisoning. Then, the contents of malondialdehyde, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine, as well as superoxide dismutase activity in the serum, cortex and hippocampus were detected by ELISA. Additionally, the mRNA and protein expression levels of Nrf2 and downstream genes were detected by RT-PCR and Western blotting, respectively.: Our results showed that CO poisoning significantly impaired neurological function which was improved over time, and HCH markedly attenuated neurological impairment following CO poisoning. In addition, CO poisoning resulted in increased levels of malondialdehyde, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine and markedly reduced superoxide dismutase activity at 1 and 9 days, which were significantly inhibited by HCH at 9 days. Finally, CO poisoning increased the mRNA and protein levels of Nrf2 and downstream genes, and HCH further induced the anti-oxidative capability.: These findings indicate the neuroprotective effects of HCH on DEACMP, which are related to the activation of Nrf2 signaling pathway.

Hydrogen gas protects against delayed encephalopathy after acute carbon monoxide poisoning in a rat model.

Carbon monoxide (CO) has been the leading cause of poisoning mortality in many countries and hyperbaric oxygen (HBO) is a widely accepted treatment for CO poisoning. However, some patients with CO poisoning will still develop neurocognitive sequelae regardless of HBO therapy, which can persist since CO poisoning or be present days to weeks after a recovery from CO poisoning. HBO has been used in the prevention and treatment of neurocognitive sequelae after CO poisoning, and some mechanisms are also proposed for the potential neuroprotective effects of HBO on the neurocognitive impairment after CO poisoning, but there is still controversy on the effectiveness of HBO on neurocognitive sequelae after CO poisoning. In this paper, we briefly introduce the neurocognitive sequelae after CO poisoning, summarize the potential predictive factors of neurocognitive sequelae, and discuss the use of HBO in the treatment and prevention of neurocognitive sequelae after CO poisoning.

Neurocognitive sequelae after carbon monoxide poisoning and hyperbaric oxygen therapy.

Roflumilast is an inhibitor of phosphodiesterase-4 (PDE4) and can suppress the hydrolysis of cAMP in inflammatory cells, conferring anti-inflammatory effects. This study aimed to investigate the protective effects of roflumilast on hyperoxia-induced acute lung injury (HALI) in a rat model. Male Sprague-Dawley rats were randomly assigned into: control group; HALI group; 2.5 mg/kg roflumilast group; and 5 mg/kg roflumilast group. Rats were pressurized to 250 kPa with pure oxygen to induce lung injury. In the roflumilast groups, rats were orally administered with roflumilast at 2.5 or 5 mg/kg once before hyperoxia exposure and once daily for two days after exposure. Rats were sacrificed 72 hours after hyperoxia exposure. The lung tissues were collected for the detection of lung water content, inflammatory cytokines and NF-κB/p-NF-κB protein expression, and the bronchoalveolar lavage fluid was harvested for the measurement of protein concentration and lactate dehydrogenase activity. Results showed roflumilast at different doses could significantly reduce lung edema, improve lung pathology and reduce the expression of inflammatory cytokines in the lung. The protective effects seemed to be related to the dose of roflumilast. Our study indicates roflumilast has the potential as a medication for the treatment of HALI.

Roflumilast, a phosphodiesterase-4 inhibitor, improves hyperoxia-induced lung injury via anti-inflammation.

Decompression sickness (DCS) is a systemic pathophysiological process featured by bubble load. Lung dysfunction plays a harmful effect on off-gassing, which contributes to bubble load and subsequent DCS occurrence. This study aimed to investigate the effects of pulmonary surfactant on DCS as it possesses multiple advantages on the lung. Rats were divided into three groups: the normal ( = 10), the surfactant ( = 36), and the saline ( = 36) group. Animals in surfactant or saline group were administered aerosol surfactant or saline 12 h before a stimulated diving, respectively. Signs of DCS were recorded and bubble load was detected. The contents of phospholipid and surfactant protein A (SPA), protein, IL-1 and IL-6 in bronchoalveolar lavage fluid (BALF), and lung wet/dry (W/D) ratio were determined. Serum levels of IL-6, ICAM-1, E-selectin, GSH, and GSSG were detected. In surfactant-treated rats, the morbidity and mortality of DCS markedly decreased ( < 0.01 and  < 0.05, respectively). Survival time prolonged and the latency to DCS dramatically delayed ( < 0.01). More importantly, bubble load markedly decreased ( < 0.01). The increases of protein, IL-1 and IL-6 in BALF, and lung W/D ratio were alleviated. Restoration of total phospholipid and SPA in BALF and ICAM-1 and E-selectin in serum was observed. The inflammation and oxidation were attenuated ( < 0.01). In conclusion, prediving administrating exogenous surfactant by aerosolization is an efficient, simple, and safe method for DCS prevention in rats. This is the first study exploring the effects of aerosol surfactant on DCS prevention and it was proven to be an efficient and simple method. The role of surfactant in facilitating off-gassing was thought to be the critical mechanism in bubble degrading and subsequent DCS prevention.

Protective effects of pulmonary surfactant on decompression sickness in rats.

Our previous studies have indicated that heliox preconditioning (HePC) may exert neuroprotective effects on neonatal hypoxic-ischemic encephalopathy (HIE). The present study was to investigate whether HePC alleviates neonatal HIE by inhibiting necroptosis and explore the potential mechanism. Seven-day-old rat pups were randomly divided into Sham group, HIE group, HIE + HePC group, HIE + Dantrolene (DAN) group, and HIE + Necrostatin-1 (Nec-1) group. HIE was induced by common carotid artery ligation and subsequent hypoxia exposure. The neurological function, brain injury, and molecular mechanism were evaluated by histological staining, neurobehavioral test, Western blotting, Ca, immunofluorescence staining, co-immunoprecipitation (Co-IP), and transmission electron microscopy (TEM). Results supported that the expression of necroptosis markers and p-RyR2 in the brain increased significantly after HIE. HePC, DAN, or Nec-1 was found to improve the neurological deficits after H/I and inhibit neuronal necroptosis. Interestingly, both HePC and DAN inhibited the increases in cytoplasmic Ca and CaMK-II phosphorylation in the brain secondary to HIE, but Nec-1 failed to affect Ca. In conclusion, our results suggest HePC may alleviate cytoplasmic Ca overload by regulating p-RyR2, which inhibits the necroptosis in the brain, exerting neuroprotective effects on HIE.

Heliox Preconditioning Exerts Neuroprotective Effects on Neonatal Ischemia/Hypoxia Injury by Inhibiting Necroptosis Induced by Ca Elevation.

The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa.

Stroke is a leading cause of mortality and disability worldwide. Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of stroke-induced brain injury. Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology. Recently, a new type of post-translational modification, known as lysine succinylation, has been recognized to play a significant role in mitochondrial energy metabolism after ischemia. However, the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood. We aimed to review the effects of succinylation on energy metabolism, reactive oxygen species generation, and neuroinflammation, as well as Sirtuin 5 mediated desuccinylation after stroke. We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke. The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases. Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes. Sirtuins, especially Sirtuin 5, are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes. Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke. Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism, and neuroprotective effects of these agents have been observed in experimental stroke studies. However, their therapeutic efficacy in stroke patients should be validated.

Succinylation modification: a potential therapeutic target in stroke.

Assessment of hyperbaric hyperoxic lung injury in rats.

High-altitude pulmonary edema (HAPE) is a common disease observed in climbers, skiers and soldiers who ascend to high altitudes without previous acclimatization. Thus, a reliable and reproducible animal model that can mimic the mechanisms of pathophysiologic response in humans is crucial for successful investigations. Our results showed that exposure to 4500 m for 2 days had little influence on lung function or blood gas, and exposure to 6000 m for 2 or 3 days could change lung function and blood gas, but most parameters returned to nearly normal levels within 48 hours. This study indicates that exposure to 6000 m for 3 days may induce evident lung edema and significantly alter lung function and blood gas, which may mimic HAPE in clinical practice. Thus, this animal model of HAPE may be used in future studies on HAPE.

Lung function and blood gas of rats after different protocols of hypobaric exposure.

Decompression after diving may inevitably cause the production of bubbles in the body, even without protocol violation. Bubbles produced in the circulation may damage the vascular cells, leading to vascular dysfunction. In this study, five subjects were recruited and subjected to hyperbaric exposure (15 meters; 100 minutes). The function of the brachial artery was assessed by measuring diameter, systolic peak velocity (SPV), resistance index (RI), and flow-mediated dilation (FMD) of the brachial artery before and after hyperbaric exposure. Our results showed that hyperbaric air exposure slightly increased the diameter of the brachial artery and significantly increased its RI but reduced the FMD and markedly decreased the SPV. This study indicates that hyperbaric air exposure at low pressure may also alter the function of the brachial artery.

Wenwu Liu

Department of Diving and Hyperbaric Medicine,
Naval Medical Center,
Department of Diving and Hyperbaric Medicine, Naval Medical Center

Naval Medical University

A Modified Method for Intrathecal Catheterization in Rats

Wenwu Liu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Diving and Hyperbaric Medicine,Naval Medical Center,Department of Diving and Hyperbaric Medicine, Naval Medical Center

Naval Medical University

A Modified Method for Intrathecal Catheterization in Rats

Department of Diving and Hyperbaric Medicine,
Naval Medical Center,
Department of Diving and Hyperbaric Medicine, Naval Medical Center