Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke.

BACKGROUND: Ischemic stroke triggers inflammatory responses and oxidative stress in the brain, and microglia polarization affects the degree of neuroinflammation. It has been reported that the inhibition of soluble epoxide hydrolase (sEH) activity protects brain tissue. However, the anti-inflammatory and antioxidative effects of sEH inhibition in the ischemic brain are not fully understood. This study aimed to investigate the effects of a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), after ischemic stroke. METHODS: Adult male rats with middle cerebral artery occlusion (MCAO) were administered with AUDA or a vehicle. Behavioral outcome, infarct volume, microglia polarization, and gene expression were assessed. RESULTS: Rats treated with AUDA showed better behavioral outcomes and smaller infarct volumes after MCAO. After AUDA treatment, a reduction of M1 microglia and an increase of M2 microglia occurred at the ischemic cortex of rats. Additionally, there was an increase in the mRNA expressions of antioxidant enzymes and anti-inflammatory interleukin-10, and pro-inflammatory mediators were decreased after AUDA administration. Heme oxygenase-1 was mainly expressed by neurons, and AUDA was found to improve the survival of neurons. CONCLUSION: The results of this study provided novel and significant insights into how AUDA can improve outcomes and modulate inflammation and oxidative stress after ischemic stroke.

Development of a Modified Surgical Technique for Simulating Ischemic Cerebral Cortex Injury in Rats.

BACKGROUND/AIM: Middle cerebral artery occlusion (MCAO) in rodents is an essential animal model for research focusing on ischemic stroke. To date, several kinds of surgical methods for MCAO have been developed and the craniotomy method has the advantage of direct visualization of the middle cerebral artery (MCA). MCAO at a more proximal site produces better surgical results, but it is a more invasive technique. The aim of this study was to evolve the surgical technique for simulating ischemic cerebral cortex injury in rats. MATERIALS AND METHODS: To approach proximal MCA with a less invasive procedure, a modified surgical technique for MCAO in rats was developed. Besides, rats receiving the modified and conventional method were compared with regard to infarct volume and by behavioral tests. RESULTS: Following craniotomy, we proposed that the inferior edge of the craniotomy should be enlarged with fine forceps. This modified surgical method induces larger infarct volume, significant behavioral impairment and can induce ischemic stroke. Additionally, it does not significantly increase the operation time, and has produced no obvious complications. CONCLUSION: This modified surgical technique may serve as a practical method for performing MCAO.

Inhibition of soluble epoxide hydrolase regulates monocyte/macrophage polarization and improves neurological outcome in a rat model of ischemic stroke.

It is generally understood that continuing neuroinflammation after ischemic stroke can exacerbate the brain damage. During the inflammatory hematogenous recruitment process, the monocytes and macrophages are activated into proinflammatory M1 and anti-inflammatory M2 cell types. Inhibition of soluble epoxide hydrolase (sEH) activity has been reported to regulate monocytes/macrophages, and attenuates neuroinflammation. This study aimed to evaluate whether a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), can regulate monocyte/macrophage polarization and improve motor function in the rats with ischemic stroke induced by middle cerebral artery occlusion. We measured the infarct volume with 2,3,5-triphenyltetrazolium chloride staining and used the rotarod test to assess motor performance in rats. The monocyte/macrophage activation and mRNA expression of proinflammatory mediators were measured by flow cytometry and reverse-transcription quantitative PCR, respectively. Our results showed better neurological function and less infarct volume in the rats treated with AUDA. Compared with the vehicle group, the AUDA-treated group showed a reduction in M1 monocyte/macrophage activation and proinflammatory mRNA expressions in the infarct cortex of rats. Our data suggest that the sEH inhibition may regulate monocyte/macrophage polarization and improve neurological outcome after ischemic stroke.

Os(II) phosphors with near-infrared emission induced by ligand-to-ligand charge transfer transition.

Heating of Os3(CO)12 with 6 equiv of 2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl) pyridine (fptzH) in refluxing diethylene glycol monomethyl ether, followed by sequential treatment with stoichiometric Me3NO and addition of PPhMe2, afforded two isomeric mixtures of red-emitting [Os(fptz)2(PPhMe2)2] (1T and 1C), for which the notations T and C stand for the trans and cis-oriented fptz chelates, respectively. Alternatively, preparation of Os(II) complex using a 1:1 mixture of 5,5'-di(trifluoromethyl)-3,3'-di-1,2,4-triazole (dttzH2) and 2,2'-bipyridine (bpy), instead of fptzH, gave isolation of a mononuclear Os(II) complex [Os(bpy)(dttz)(CO)2] (2) in moderate yield. Replacement of CO with PPhMe2 on 2 afforded near-infrared (NIR)-emitting Os(II) complex [Os(bpy)(dttz)(PPhMe2)2] (3). The single-crystal X-ray structural analyses were executed on 1C, 2, and 3 to reveal the structural influence imposed by the various chelates. The photophysical and electrochemical properties were measured and discussed using the results of density functional theory (DFT) and time-dependent DFT calculations. Complex 3 is selected as the dopant to probe its electroluminescent properties by fabrication of the NIR emitting organic light-emitting diodes.