TFP5 prevents 1-methyl-4-phenyl pyridine ion-induced neurotoxicity in mouse cortical neurons.

The present study aimed to investigate the protective effect of a modified p5 peptide, TFP5, on 1-methyl-4-phenyl pyridine ion (MPP+)-induced neurotoxicity in cortical neurons and explore the therapeutic effect of TFP5 on Parkinson's disease (PD). MPP+ was applied to a primary culture of mouse cortical neurons to establish the cell model of PD. Neurons were divided into four groups: Control, model (MPP+), scrambled peptide (Scb) (Scb + MPP+) and TFP5 (TFP5 + MPP+) groups. Pretreatment with Scb or TFP5 was applied to the latter two groups, respectively, for 3 h, while phosphate-buffered saline was applied to the control and model groups. MPP+ was then applied to all groups, with the exception of the control group, and neurons were cultured for an additional 24 h. Neuron viability was evaluated using a Cell Counting kit-8 (CCK8) assay. To explore the mechanism underlying the protective effects of TFP5, the expression levels of p35, p25 and phosphorylated myocyte enhancer factor 2 (p-MEF2D) were determined by western blotting. Fluorescence microscopy showed that TFP5 was able to pass through cell membranes and distribute around the nucleus. CCK8 assay showed that neuronal apoptosis was dependent on MPP+ concentration and exposure time. Cell viability decreased significantly in the model group compared with the control group (55±7 vs. 100±0%; P<0.01), and increased significantly in the TFP5 group compared with the model group (98±2 vs. 55±5%; P<0.01) and Scb group (98±2 vs. 54±4%; P<0.01). Scb exhibited no protective effect. Western blotting results showed that MPP+ induced p25 and p-MEF2D expression, TFP5 and Scb did not affect MPP+-induced p25 expression, but TFP5 reduced MPP+-induced p-MEF2D expression. In summary, TFP5 protects against MPP+-induced neurotoxicity in mouse cortical neurons, possibly through inhibiting the MPP+-induced formation and elevated kinase activity of a cyclin-dependent kinase 5/p25 complex.

Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats.

In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors. No protective effects were observed when hypothermia was induced too long after MCAO. At 6h after MCAO onset, hypothermia alone failed to decrease cerebral edema and infarct volume, but the combination of glibenclamide and hypothermia decreased both. The combination also improved neurological outcome, ameliorated blood-brain barrier damage and decreased levels of COX-2, TNF-α and IL-1ß. These results suggest that glibenclamide enhances and extends the therapeutic effects of delayed hypothermia against ischemia stroke, potentially by ameliorating blood-brain barrier damage and declining levels of pro-inflammatory factors.

[Pathologic changes of the palatopharyngeal muscles in adult patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To investigate the pathology of palatopharyngeal muscle obtained from patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: The samples from both groups were studied under HE, nicotinamide adenine dinucleotide-tetrazolium reductase (NADH- TR), modified Gomori trichrome (MGT) and adenosine triphosphatase (ATPase) staining. There were 36 cases of OSAHS who received uvulopalatopharyngoplasty in the experimental group (including 6 mild, 6 moderate and 24 severe cases). There were 6 patients with chronic tonsillitis but without OSAHS as matched control group. Both groups were diagnosed by PSG. RESULTS: Centralized located nuclei and obvious variability of the size of fiber types were observed in both groups. The occurrence rate of the former were 1/6 in control group and 52.8% (19/36) in OSAHS, while the rate of the latter were 4/6 and 58.3% (21/36)respectively. A large number of fibers in both groups (control group 5/6, OSAHS group 28/36) presented an irregularly distributed staining for oxidative activity reaction in NADH stain.Endomysium connective tissue proliferation, a lobular or motheaten appearance, target-like fibers, ragged red fiber (RRF) and muscle necrosis were only observed in OSAHS group.While it was more common in serious OSAHS patients. Dominance of type 1 fibers were observed in matched control group in ATPase stain. Clusters of type 2 fibers or clusters of both type fibers were observed in OSAHS, especially more common in serious OSAHS. There was a predominance of the type 2 fibers in some OSAHS patients. CONCLUSIONS: The observation of HE and special muscular stain identified that palatopharyngeal muscle of OSAHS patients had pathological lesion. The pathological changes included muscular lesion and abnormal distribution of different fiber types, the rate of type 1 fiber which maintained the opening of upper air way decreased.