Kv7 channels, especially Kv7.2 (KCNQ2) and Kv7.3 (KCNQ3), are key determinants for membrane excitability in the brain. Some chemical modulators of KCNQ channels are in development for use as anti-epileptic drugs, such as retigabine (D-23129, N-(2-amino-4-(4-fluorobenzylamino)-phenyl)), which was recently approved for clinical use. In addition, several other compounds were also reported to potentiate activity of the Kv7 channels. It is therefore of interest to investigate compound-channel interactions, so that more insights may be gained to aid future development of therapeutics. We have conducted a screen of 20,000 compounds for KCNQ2 potentiators using rubidium flux combined with atomic absorption spectrometry. Here, we report the characterization of a series of new structures that display isoform specificity and induce a marked reduction of deactivation distinct from that of retigabine. Furthermore, KCNQ2(W236L), a previously reported mutation that abolishes sensitivity to retigabine, remains fully sensitive to these compounds. This result, together with mutagenesis and other studies, suggests that the reported compounds confer a unique mode of action and involve new molecular determinants on the channel protein, consistent with the idea of recognizing a new site on channel protein.

The effects of EA L14 in regulating cerebral activities could be displayed and recorded through BOLD fMRI, the distribution of signally deactivated area evoked by EA L14 was similar to the known distribution of anatomical orientation of pain in brain, and closely related to the anatomic structure of limbic system, which areas are possibly the acupuncture analgesic effect's cerebral regulating area. Furthermore, activated portion of left central anterior gyrus, which represent the movement of oral facial muscles, and the activated portion of cerebellum are possibly related with the effect of using EA L14 in treating facial palsy and facial muscle spasm. As for the mechanism of signal deactivation of cerebral activities exhibited in the present study that is unable to be elucidated, it awaits for further research.

Parkinson’s disease (PD) is characterized by pathological changes within several deep structures of the brain, including the substantia nigra and caudate nucleus. However, changes in interstitial fluid (ISF) flow and the microstructure of the interstitial space (ISS) in the caudate nucleus in PD have not been reported. In this study, we used tracer-based magnetic resonance imaging (MRI) to quantitatively investigate the alterations in ISS and visualize ISF flow in the caudate nucleus in a rotenone-induced rat model of PD treated with and without madopar. In the rotenone-induced rat model, the ISF flow was slowed and the tortuosity of the ISS was significantly decreased. Administration of madopar partially prevented these changes of ISS and ISF. Therefore, our data suggest that tracer-based MRI can be used to monitor the parameters related to ISF flow and ISS microstructure. It is a promising technique to investigate the microstructure and functional changes in the deep brain regions of PD.

The present study investigated the application of the T1ρ and T2 relaxation mapping magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the evaluation of intervertebral disc degeneration (IDD). A total of 93 asymptomatic subjects were imaged with T1ρ and T2 mapping, as well as DWI. Pfirrmann grading was performed and correlation analysis was conducted for T1ρ, T2 and DWI results with the grading results and age. Pfirrmann grading indicated 69 cases of grade I, 240 cases of grade II, 101 cases of grade III, 43 cases of grade IV and 12 cases of grade V. MRI showed that the T1ρ values of the nucleus pulposi at L4/5 and L5/S1 were significantly reduced (P<0.05) and no significant differences were observed in the T2 values compared with the values of the nucleus pulposus at L1/2, L2/3 and L3/4. The apparent diffusion coefficient (ADC) values of L1/2 were significantly decreased from L2/3 and L3/4 (P<0.05). Correlation analysis revealed that the T1ρ, T, and ADC values were positively correlated with each other. Moreover, the T1ρvalues were significantly decreased with the increase of Pfirrmann grades (P<0.05), with the exception of grades IV and V. However, T2 and ADC values were not significantly different between grades I and II or IV and V. In addition, the T1ρ, T2 and ADC values were significantly decreased with the increase of age in patients with IDD (P<0.05). T1ρ and T2 mapping and DWI are promising techniques for the in vivo diagnosis of IDD, which may be useful in determining the appropriate prevention and treatment options for the disease.