ABSTRACT
BACKGROUND@#The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration. @*METHODS@#In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso–Beattie– Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining. @*RESULTS@#The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements. @*CONCLUSION@#Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.
ABSTRACT
BACKGROUND: There are pressure sensors in carotid-sinus, which are very sensitive to blood pressure regulated by ions and play an important role in the regulation of blood pressure. But it is yet not very clear how different ions regulate the blood pressure through pressure sensors in carotidsinus.OBJECTIVE: To observe the effect of different ions at various concentrations outside the carotid-sinus.DESIGN: Self-control experiment.SETTING: Preclinical Experiment Center, Fourth Military Medical University of Chinese PLA.MATERIALS: The experiment was accomplished in the Preclinical Experiment Center, Fourth Military Medical University of Chinese PLA from December 2000 to June 2001. Totally 18 New Zealand pure strain rabbits were provided by the Aninal Experimenting Center of Fourth Military Medical University of Chinese PLA. They were standard grade Ⅱ, of either gender and body mass was (2.0±0.2) kg.METHODS: The rabbits were divided into Na+, K+ and Ca2+ groups according to random numbers, and each group consisted of 6 rabbits. After anaesthesia, tracheal intubatton was performed on the rabbit, and bilateral carotid arteries were separated with carotid-sinus separated on one side and vessel intubatton performed in the other side for blood pressure measurement. Then various concentrations of Na+, K+ and Ca2+ ions were added outside the carotid-sinus with the pipette to make the carotid-sinus completed immersed in the ion solutions. The basal blood pressure and the peak value after ions addition were recorded respectively.MAIN OUTCOME MEASURES: The basal blood pressure and the peak value after ions addition.RESULTS: After Na+ (0.15, 1.5 mol/L) was added the blood pressure was(97±12), (83±17) mm Hg. It was decreased significantly compared with the basal value (106±14), (105±12) mm Hg (t=2.946, P ＜ 0.05). K+ (0.4 mol/L)decreased the blood pressure significantly [(106±12), (64±13) mm Hg, (t=13.496, P ＜ 0.01)], but other concentrations of K+ were not effective. Ca2+(0.07 mol/L) increased the blood pressure to (113±16) mm Hg compared with the basal value (103±12) mm Hg (t=-3.627, P ＜ 0.01).CONCLUSION: Na+, K+ and Ca2+ regulate the blood pressure by acting on the carotid-sinus directly. High concentrations of Na+ and K+ possess the effect of decreasing the blood pressure, while high concentrations of Ca2+increases it, which may be an important mechanism of blood pressure regulation.
ABSTRACT
The mathematical models for simulation of cardiac sodium, potassium and calcium channel kinetics courses and currents were developed to simulate the properties of ionic currents and channel dynamic courses. With modifications of these models, it is possible to make them integrated for simulating the whole process of action potential, thus additional discussion on ionic mechanism could provide a theoretical foundation for further animal experiments and clinical applications.
Subject(s)
Action Potentials , Algorithms , Calcium Channels , Physiology , Computer Simulation , Ion Channels , Physiology , Membrane Potentials , Models, Cardiovascular , Myocytes, Cardiac , Physiology , Potassium Channels , Physiology , Sodium Channels , PhysiologyABSTRACT
AIM To study the effect of CGRP on L-type calcium channel current in guinea pig ventricular myocytes under normal and imitating ischemia and hypoxia conditions. METHOD The whole-cell patch clamp recording technique was used. RESULTS When the ventricular cell was held at -40 mV and depolarized to 0 mV, 1?10 -9 、1?10 -8 and 1?10 -7 mol?L -1 CGRP increased I Ca-L from(1 26?0 18)nA ( n =8) to (1 87?0 25)nA ( P