ZL006 promotes migration and differentiation of transplanted neural stem cells in male rats after stroke.

New strategies must be developed to resolve the problems of stroke treatment. In recent years, stem cell-based therapy after stroke has come into the public and academic lens. Previously we have shown that uncoupling neuronal nitric oxide synthase (nNOS) from the postsynaptic density protein-95 (PSD-95) by ZL006, a small molecular compound, can ameliorate ischemic damage and promote neuronal differentiation of endogenous neural stem cells (NSCs) in focal cerebral ischemic male rats. In this study, we transplanted exogenous NSCs into the ipsilateral hemisphere of male rats in combination with ZL006 treatment after ischemic stroke. We show that ZL006 treatment facilitates the migration of transplanted NSCs into the ischemia-injured area and promotes neuronal differentiation of these cells, which is not due to a direct effect of ZL006 on exogenous NSCs but is associated with increased phosphorylation of cAMP response element-binding protein (CREB) in neurons and favorable microenvironment. Moreover, improved functional outcome in the ZL006-treated group was also found. Taken together, our data indicate that ZL006, uncoupling nNOS-PSD-95 in neurons, positively regulates the fate of transplanted NSCs and benefits the functional outcome after stroke in male rats.

Comparison of periodontal ligament anesthesia and submucosal infiltration anesthesia in healthy volunteers.

OBJECTIVE: To compare periodontal ligament anesthesia using a computer-controlled local anesthetic delivery system (C-CLADS) and submucosal infiltration anesthesia using a manually operated syringe in terms of the injection pain, anesthetic effect, anesthetic dose, and complications in healthy volunteers. METHODS: Fifty healthy volunteers, aged 18 to 56 years, were recruited from September 2012 to May 2013 in the Department of Stomatology of Peking Union Medical College Hospital. A randomized self-controlled trial was conducted by applying a periodontal ligament anesthesia on one side and conventional manual submucosal infiltration anesthesia to the other (control) side. The differences in the onset time of anesthesia, drug dosage, anesthetic effect, and the degree of injection pain were compared. The complications associated with the two anesthesia methods were also recorded. RESULTS: When using C-CLADS to perform a periodontal ligament anesthesia, the drug dosage and the severity of injection pain were significantly less than those of conventional manual infiltration anesthesia [drug dosage: (0.34±0.09)ml vs.(0.55±0.13)ml, P<0.01; VRS: 0.42±0.73 vs. 1.38±0.92, P<0.01; VAS: 1.34±1.21 vs. 3.10±1.70, P<0.01]. The anesthesia success rate was approximately 90.0%, showing no significant difference relative to conventional submucosal infiltration anesthesia. Approximately 24% of the volunteers experienced postoperative pain after periodontal ligament anesthesia. CONCLUSION: Compared with conventional submucosal infiltration anesthesia using manual syringes, periodontal ligament anesthesia performed using C-CLADS can reduce the injection pain and drug dosage while achieving a satisfactory anesthetic effect; however, a considerable proportion of cases may experience postoperative pain.

(+)-Borneol is neuroprotective against permanent cerebral ischemia in rats by suppressing production of proinflammatory cytokines.

Stroke is one of the leading causes of disability and death globally. It occurs when a major artery is occluded in the brain and leads to death of cells within the injured tissue. (+)-Borneol, a simple bicyclic monoterpene extracted from traditional Chinese medicine, is widely used in various types of diseases. However, no study has proved the effects of (+)-borneol on functional recovery from permanent ischemic stroke and the mechanism is still unknown. Here, we report that in the rat model of permanent cerebral ischemia, we found that (+)-borneol (1.0 mg/kg) significantly ameliorated infarct size and neurological scoresvia reducing the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) in a dose dependent manner. Notably, (+)-borneol showed long-term effects on the improvement of sensorimotor functions in the photothrombotic model of stroke, which decreased the number of foot faults in the grid-walking task and forelimb asymmetry scores in the cylinder task, at least in part through reducing loss of dendritic spines in the length, brunch number and density. These findings suggest that (+)-borneol could serve as a therapeutic target for ischemic stroke.