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Background Traumatic brain injury (TBI) is a kind of brain structure destruction and brain dysfunction syndrome caused by mechanical injury. At present, the treatment of traumatic brain injury is mainly neuroprotective drugs, but the efficacy is limited. Therefore, the exploration of effective therapeutic targets for traumatic brain injury has become a key scientific problem in current neuropharmacological research. Studies have found that neuroinflammation is closely related to the occurrence and development of traumatic brain injury. After activation of central microglia cell, various cellular inflammatory factors will be secreted, causing damage to the central nervous system and causing neuroinflammation. Studies have shown that potassium channel Kv1.3 plays a crucial role in microglia-mediated neuroinflammation, but the mechanism of microglial potassium channel Kv1.3 on traumatic brain injury remains unclear. Methods In this study, the functional localization of potassium channel Kv1.3 in microglia cell was investigated by behavioral observation, patch clamp, immunofluorescence, Western blotting, real-time PCR and other techniques in mice model of repetitive traumatic brain injury combined with Kv1.3 gene knockout mice. Results We found significant neurological deterioration in TBI mice, and knockdown of Kv1.3 effectively reversed TBI-mediated neurological dysfunction. The expression of inflammatory factors IL-1β and TNF-α was significantly increased in the hippocampus of mice with traumatic brain injury, and the down-regulation of Kv1.3 gene significantly inhibited the expression of these inflammatory factors. Conclusion Potassium channel Kv1.3 in microglia cell is an important regulatory target in repetitive traumatic brain injury.

Chan-su (toad venom) has been used as an analgesic agent in China from ancient to modern times. Bufalin, a non-peptide toxin extracted from toad venom, is considered as one of the analgesic components. The molecular mechanism underlying the anti-nociceptive effects of bufalin remains unclear so far. In this study, we investigated the pharmacological effects of bufalin on pain-related ion channels as well as animal models through patch clamping, calcium imaging and animal behavior observation. Using the whole-cell recording, bufalin caused remarkable suppressive effect on the peak currents of Nav channels (voltage gated sodium channels, VGSCs) of dorsal root ganglion neuroblastomas (ND7-23 cell) in a dose-dependent manner. Bufalin facilitated the voltage-dependent activation and induced a negative shift on the fast inactivation of VGSCs. The recovery kinetics of VGSCs were significantly slowed and the recovery proportion were reduced after administering bufalin. However, bufalin prompted no significant effect not only on Kv4.2, Kv4.3 and BK channels heterologously expressed in HEK293T cells, but also on the capsaicin and allyl isothiocyanate induced Ca2+ influx. What's more, bufalin could observably relieve formalin-induced spontaneous flinching and licking response as well as carrageenan-induced thermal and mechanical hyperalgesia in dose-dependent manner in agreement with the results of in vitro experiments. The present results imply that the remarkable anti-nociceptive effects produced by bufalin are probably ascribed to its specific regulation on Nav channels. Bufalin inhibits the Nav channels in a dose-dependent manner, which will provide references for the optimal dose selection of analgesia drugs.

Mast cells (MCs) degranulation is a key process during the allergic inflammatory response. MCs release their preformed and new synthesized granules after activation. We found that granules were released partially and selectively after the activation of bone marrow-derived mouse mast cells (BMMCs). Next, we investigated the response of degranulated MCs to a new challenge. BMMCs were activated by antibody/antigen (IgE/Ag) or compound 48/80 (C48/80). The degranulated BMMCs were then reactivated by either IgE/Ag or C48/80 without time intervals. Flow cytometry was used to detect the expression of CD117, FcεRI, and intracellular granules of BMMCs, and BMMCs degranulation was detected using the β-hexosaminidase release assay. The morphology of BMMCs was observed by staining with toluidine blue. Degranulated BMMCs activated by IgE/Ag failed to respond to the same IgE/Ag challenge and released β-hexosaminidase independent of unoccupied FcεRI, but responded to C48/80. Degranulated BMMCs activated by C48/80 responded to either IgE/Ag or C48/80. These results indicated that degranulated BMMCs could be reactivated and released granule mediators again, this revealed the unique mediator releasing mechanism of degranulated MCs and their potential function in maintaining inflammation or causing hypersensitivity.

Deep brain stimulation (DBS) is routinely used in the treatment of Parkinson’s disease, tremor disease, dystonia, and epilepsy. This study aims to establish a hemiparkinsonian monkey model and to investigate the effect of implanted human DBS system for the chronic alleviation of parkinsonian symptoms. Hemiparkinsonism was induced in four rhesus monkeys by unilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. DBS leads were implanted stereotaxically in the right subthalamic (STN) of the monkeys. Subcutaneous extension wires were used to connect the leads to the internal pulse generators (IPG) for stimulation in two of the monkeys (human DBS test group). Post-operative imaging studies confirmed optimal locations of lead contacts. One week later, the IPG was turned on to determine the optimal stimulating parameters, using apomorphine (APO)-induced rotation as a behavioral readout. Animal behavior was scored on a scale of 0–10 over a 12-month period using the modified disability rating scale of hemiparkinsonian monkeys (DRSH). Parkinsonian symptoms in the group of monkeys with DBS improved dramatically (DRSH 3–4) compared to controls (DRSH 7–8). DBS leads were within the STN without intracranial hemorrhage, infection, or other serious complications. Histological examination showed cell necrosis and lymphocytic infiltration of the tissues around the lead and STN gliosis surrounding the lead contact. This study demonstrates that therapeutically effective human DBS systems can be established in relevant disease models in monkeys. Such combination of human DBS systems in hemiparkinsonian monkeys should be valuable in studying the mechanism of action and chronic consequences of DBS therapy in humans.