Recent studies indicate that over-activation of Cdk5 is a crucial pro-death signal and Cdk5 activity inhibition provides neuroprotection in animal stroke models. However, Cdk5 inhibitors are reported to affect physiological functions of Cdk5 and lead to serious side effects. Therefore, targeting Cdk5 or its activators without affecting physiological functions of Cdk5 is a therapeutic strategy for ischemic brain injury. In this study, we examined Cdk5 activity in a rat hypoxia/ischemia (HI) injury model. Cdk5 expression was not changed after HI injury, but Cdk5 activity significantly increased, which was demonstrated by the increased phorsphorylation-phosphorylation of Tau and glucocorticoid receptor (GR), two downstream signals of Cdk5. We further showed that the levels of Cdk5 activators p35 and p39 decreased after HI injury, while p25, which is converted from p35 and has a higher activator activity on Cdk5, increased markedly after HI injury. P5, a 24-residue mimetic peptide of p35, was reported to specifically inhibit the p25/Cdk5 signal pathway in an Alzheimer's disease model. P5-TAT, which can cross the blood-brain barrier and cell membrane facilitated by TAT protein, was used in our study. We found that p5-TAT treatment did not change the levels of p35, p39, and p25, but reduced the phorsphorylation of Tau and GR, suggesting the inhibition of the p25/Cdk5 by the peptide p5-TAT. This was supported by the fact that p5 interacted with Cdk5, but not with Cdk5 activators. In addition, p5-TAT reduced cleaved caspase-3 level, a marker of neuronal apoptosis. We further demonstrated that p5-TAT pre-treatment reduced cerebral infarct volume; even when p5-TAT was delayed to be administered at 24h after HI injury, p5-TAT still promoted long-term functional recovery. Therefore, Cdk5 inhibition by the small peptide p5-TAT or its derivatives is a promising therapeutic strategy for the treatment of ischemic brain injury including hypoxic-ischemic encephalopathy and stroke.

Abstract Staphylococcus aureus was used as an indicator to study the origin and spread of microbial aerosol in and around chicken houses. Air samples indoor, upwind (10 and 50 m), and downwind (10, 50, 100, 200, and 400 m) of four chicken houses were collected using Andersen‐6 stages sampler. The concentrations of S. aureus were determined for every sample site. Isolation of S. aureus from chicken feces was performed according to the standard method. The genetic relationship among the isolates was determined by profiles of PCR‐amplified repetitive extragenic palindromic (REP‐PCR) elements. The results showed that the concentrations of S. aureus indoor of four chicken houses were higher than those upwind and downwind sites (P < 0.05 or P < 0.01), but there were no significant concentration differences among downwind sites (P > 0.05). The fingerprints and the phylogenetic tree indicated that a part of the S. aureus (55.6%, 10/18) isolates from indoor air had the same REP‐PCR fingerprints as feces isolates. Consequently, most isolates (57.1%, 20/35) from downwind 10, 50, 100, 200, even 400 m had the same REP‐PCR fingerprints as those from indoor or feces. These data indicated that some isolates from downwind and indoor originated from the chicken feces. However, those isolates from upwind had low similarity (similarity index 0.6–0.87) to those from indoor or feces. Therefore, the isolates upwind were not from the chicken feces or indoor. These results suggest that microbes in chicken feces can be aerosolized and spread indoor and outdoor, especially to downwind of the chicken houses. It should have an important epidemiological and public health significance. Practical Implications Thus, the use of S. aureus as an indicator to study the origin and spread of airborne pathogens from chicken houses is potentially useful for enhancing public health and understanding the airborne epidemiology of this pathogen. Meanwhile it can provide evidence for studying the spreading model of airborne pathogens.