Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

Although N-acetylcysteine (NAC) has been shown to be neuroprotective for traumatic brain injury (TBI), the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB) and inflammatory proteins such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI

Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit

<p>Abstract</p> <p>Background</p> <p>Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH.</p> <p>Results</p> <p>Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 μm²) is significantly smaller than that in control group (462,128 ± 74,756 μm²), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 μm²) and SAH + vitamin C group (237,820 ± 21,703 μm²). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 μm², which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (<it>P </it>< 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (<it>P </it>> 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (<it>P </it>< 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so.</p

Modeling and performance analysis of marine DTN networks with Nodes-cluster in an ad hoc sub-net

The marine communication environment is complex and changeable, and the sea wireless infrastructure is few. The delay tolerant network is proposed and applied in ocean environment. We use the ships to store, carry and forward the messages, so as to solve the problem that the communication links are broken frequently and the message cannot be transmitted due to the movement of the nodes. Under the environment of MATLAB, the random motion trajectory of a fishing vessel in the South China Sea is modeled and simulated. A mobile Ad hoc network is formed between ship and ship, and the base station of the land mobile communication network is connected with the marine radio transmitting point through optical fiber. Data is generated according to Poisson distribution in a heterogeneous network at sea and the data transmission uses the flooding mechanism. Taking into account the limited capacity of the wireless transmission point of the sea, we introduced a forwarding-time-limited mechanism. The performance of it is analyzed in the delayed network at sea, and the effects of the survival time, the number of fishing vessels and the coverage of the wireless network on data delivery are compared. The simulation results show that increasing the survival time of the data and the coverage of the wireless network can improve the data delivery ratio, reduce the network transmission delay, and improve the performance of the maritime wireless communication network

The Neuroprotection of KIBRA in Promoting Neuron Survival and Against Amyloid β-Induced Apoptosis

Background: Recent research has identified the nucleotide polymorphisms of KIdney and BRAin expressed protein (KIBRA) to be associated with cognitive performance, suggesting its vital role in Alzheimer’s disease (AD); however, the underlying molecular mechanism of KIBRA in AD remains obscure.Methods: The AD animal model (APP/PS1 transgenic mice) and KIBRA knockout (KIBRA KO) mice were used to investigate pathophysiological changes of KIBRA in vivo. Mouse hippocampal cell line (HT22) was used to explore its molecular mechanism through KIBRA CRISPR/Cas9-sgRNA system and KIBRA overexpression lentivirus in vitro.Results: Aged APP/PS1 mice displayed increased neuronal apoptosis in the hippocampus, as did KIBRA KO mice. KIBRA deficiency was closely related to neuronal loss in the brain. In addition, knockdown of KIBRA in neuronal cell lines suppressed its growth and elevated apoptosis-associated protein levels under the stress of Aβ1–42 oligomers. On the contrary, overexpression of KIBRA significantly promoted cell proliferation and reduced its apoptosis. Moreover, through screening several survival-related signaling pathways, we found that KIBRA inhibited apoptosis by activating the Akt pathway other than ERK or PKC pathways, which was further confirmed by Akt-specific inhibitor MK2206.Conclusion: Our data indicate that KIBRA may function as a neuroprotective gene in promoting neuron survival and inhibiting Aβ-induced neuronal apoptosis

Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274

<p>Abstract</p> <p>Background</p> <p>c-Met is a receptor tyrosine kinase (RTK) that is over-expressed in a variety of cancers and involved in cell growth, invasion, metastasis and angiogenesis. In this study, we investigated the role of c-Met in rhabdomyosarcoma (RMS) using its small molecule inhibitor SU11274, which has been hypothesized to be a potential therapeutic target for RMS.</p> <p>Methods</p> <p>The expression level of phosphorylated c-Met in RMS cell lines (RD, CW9019 and RH30) and tumor tissues was assessed by phospho-RTK array and immunohistochemistry, respectively. The inhibition effects of SU11274 on RMS cells were studied with regard to intracellular signaling, cell proliferation, cell cycle and cell migration.</p> <p>Results</p> <p>A high level of phosphorylated c-Met was detected in 2 alveolar RMS cell lines (CW9019 and RH30) and 14 out of 24 RMS tissue samples, whereas relatively low levels of phospho-c-Met were observed in the embryonic RMS cell line (RD). The small molecule SU11274 could significantly reduce the phosphorylation of c-Met, resulting in inhibition of cell proliferation, G1 phase arrest of cell cycle and blocking of cell migration in CW9019 and RH30 cell lines.</p> <p>Conclusion</p> <p>These results might support the role of c-Met in the development and progression of RMS. Furthermore, the inhibitor of c-Met, SU11274, could be an effective targeting therapy reagent for RMS, especially alveolar RMS.</p