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Ferroptosis, an iron-dependent form of non-apoptotic cell death, plays important roles in cerebral ischemia. Previously we have found that L-F001, a novel fasudil-lipoic acid dimer with good pharmacokinetic characters has good neuroprotection against toxin-induced cell death in vitro and in vivo. Here, we investigated the protective effects of L-F001 against a Glutathione peroxidase 4 (GPX4) inhibitor Ras-selective lethality 3 (RSL3) -induced ferroptosis in HT22 cells. We performed MTT, Transmission Electron Microscope (TEM), Western blot, and immunofluorescence analyses to determine the protective effects of L-F001 treatment. RSL3 treatment significantly reduced HT22 cell viability and L-F001 significantly protected RSL3-induced cell death in a concentration-dependent manner and significantly attenuated Mitochondrial shrinkage observed by TEM. Meanwhile, L-F001 significantly decreased RSL3-induced ROS and lipid peroxidation levels in HT22 cells. Moreover L-F001could restore GPX4 and glutamate-cysteine ligase modifier subunit (GCLM) levels, and significantly deceased Cyclooxygenase (COX-2) levels to rescue the lipid peroxidation imbalance. In addition, FerroOrange fluorescent probe and Western blot analysis revealed that L-F001 treatment decreased the total number of intracellular Fe2+ and restore Ferritin heavy chain 1 (FTH1) level in RSL3-induced HT22 cells. Finally, L-F001 could reduce RSL3-induced c-Jun N-terminal kinase (JNK) activation, which might be a potential drug target for LF-001. Considering that L-F001 has a good anti-ferroptosis effect, our results showed that L-F001 might be a multi-target agent for the therapy of ferroptosis-related diseases, such as cerebral ischemia.

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Acrolein, an unsaturated aldehyde, is increased in the brain of Alzheimer's disease (AD) patients and identified as a potential inducer of sporadic AD. Synaptic dysfunction, as a typical pathological change occurring in the early stage of AD, is most closely associated with the severity of dementia. However, there remains a lack of clarity on the mechanisms of acrolein inducing AD‐like pathology and synaptic impairment. In this study, acrolein‐treated primary cultured neurons and mice were applied to investigate the effects of acrolein on cognitive impairment and synaptic dysfunction and their signaling mechanisms. In vitro, ROCK inhibitors, Fasudil, and Y27632, could attenuate the axon ruptures and synaptic impairment caused by acrolein. Meanwhile, RNA‐seq distinct differentially expressed genes in acrolein models and initially linked activated RhoA/Rho‐kinase2 (ROCK2) to acrolein‐induced synaptic dysfunction, which could regulate neuronal cytoskeleton and neurite. The Morris water maze test and in vivo field excitatory postsynaptic potential (fEPSP) were performed to evaluate spatial memory and long‐term potential (LTP), respectively. Acrolein induced cognitive impairment and attenuated LTP. Furthermore, the protein level of Synapsin 1 and postsynaptic density 95 (PSD95) and dendritic spines density were also decreased in acrolein‐exposed mice. These changes were improved by ROCK2 inhibitor Fasudil or in ROCK2 +/− mice. Together, our findings suggest that RhoA/ROCK2 signaling pathway plays a critical role in acrolein‐induced synaptic damage and cognitive dysfunction, suggesting inhibition of ROCK2 should benefit to the early AD.

Background Traumatic brain injury, one of the leading causes of death in adults under 40 years of age in the world, is frequently caused by mechanical shock, resulting in diffuse neuronal damage and long-term cognitive dysfunction. Many existing TBI animal models revival with expensive equipment or special room are needed or the processes of operations are complex and not easy to be widely used. Therefore, a simpler TBI model needs to be designed. Methods Our TBI model is an innovation of the modeling method through air guns shutting rubber bullets. A core facet is the application of our designed rubber bullet impact device. It could focus the hitting power to the fixed site of the brain, thus triggering a mild closed head injury. Moreover, the degree of damage can be adjusted by the times of shots. Results Our model induced blood-brain barrier leakage and diffused neuronal damage. Besides, it led to an increased level of Tau phosphorylation and resulted in cognitive dysfunction within several weeks post-injury. Conclusion Our TBI model is not only simple and time-saving but also can simulate mild brain injuries in clinical. It is suitable for exploring pathobiological mechanisms as well as a screening of potential therapies for TBI.

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The role of dietary fiber in highland barley in lowering blood lipids has been continuously studied in recent years. However, its effects on diabetes and diabetic nephropathy are rarely studied. Considering that highland barley bran is rich in dietary fiber, the effective use of dietary fiber in highland barley bran can not only alleviate the symptoms of diabetes but also improve the local economy. This article aimed to study the effects of highland barley fiber-rich powder (T-fiber) with a high-quality natural dietary fiber ratio (insoluble fiber/soluble fiber = 3 : 1) on the symptoms of hyperglycemia in a diabetic mouse model. Compared with the model group’s blood glucose level (30.80 mmol/L), glucose tolerance (28.57 mmol/L), and glycosylated serum protein (2.43 mmol/L), T-fiber presented significant reductions in blood glucose (23.69 mmol/L), better glucose tolerance (21.32 mmol/L), and glycosylated serum protein (1.78 mmol/L) in the diabetic mouse model. Meanwhile, T-fiber effectively alleviated hepatocellular lesions. In addition, T-fiber not only improved kidney function by reducing the 24-hour urine output (8.25 ml), urine protein levels (11.51 mg), and serum creatinine (13.80 μmol/L) but also alleviated renal pathology, including glomerular hypertrophy, mesangial expansion, and fibrosis. The above results proved the ability of T-fiber to reduce blood glucose and alleviate liver and renal function in diabetic mice. Altogether, T-fiber is a capable formula for utilizing highland barley bran dietary fiber, which alleviates diabetes symptoms and endows highland barley with promising value.