W Pan

..The presence of mAbmc1 also caused significant reduction of the influx of Abeta into the brain after perfusion. Therefore, effective antibodies to Abeta can reduce the influx of Abeta(1-40) into the brain...

..Our understanding of cytokines interacting with the BBB is still growing; not only are more cytokines being studied, but also more details of the nature of the transport systems and how they affect feeding behavior are being explored...

..Although no causal relationship can be established at this time, the behavioral changes might be related to the increased TNF alpha transport after trauma...

..This indicates the therapeutic potential of bradykinin antagonists in ameliorating tissue damage induced by SCI...

..The circadian rhythm of the influx of TNF-alpha into this region of the CNS suggests a functional role for the spinal cord in the physiological actions of TNF-alpha...

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..Knowledge of receptor-mediated regulation could facilitate effective therapeutic manipulation of BSCB permeation of vascular cytokines important to CNS regeneration...

..Exogenous TNFalpha has biphasic effects in modulating functional scores. The BBB, a dynamically regulated barrier, is actively involved in disease processes...

..We conclude that SCI by lumbar hemisection activates the transport system for TNF alpha at the BBB and suggest that selective permeation of TNF alpha may facilitate functional recovery...

..Thus, the influx of CINC1 may alter the "chemokine gradient" across the BBB and therefore affect inflammatory reactions involving the CNS...

..Better understanding of the BBB will provide insight and direction for future research in the treatment of CNS disorders...

..Together, the results show that the BBB is actively involved in the neuroendocrine regulation of feeding behavior...

..Therefore, we conclude that intact BDNF in the peripheral circulation crosses the BBB by a high-capacity, saturable transport system...

..The Ki was reduced more than 3-fold by addition of excess unlabeled CNTF. The results indicate that CNTF is saturably transported across the BBB from blood to brain...

..This suggests a function for ADM at the cerebral blood vessels, such as altering cerebral blood flow and perfusion, without disruption of the BBB...

..The results suggest that peripheral administration of neurotrophins could have therapeutic effects within the CNS...

..We conclude that IGF-1 enters the CNS by a saturable transport system at the BBB, which functions in synchrony with IGF binding proteins in the periphery to regulate the availability of IGF-1 to the CNS...

..Thus, with additional considerations such as stability and interactions with the vasculature, multiple-time regression analysis is sensitive and selective for study of the penetration of peptides across the BBB...

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..It could induce growth-promoting cytokines and neurotrophins, or it could increase the production of antiproliferative cytokines, nitric oxide, and free radicals, thereby contributing to apoptosis...

..Thus, EGF has a saturable transport system at the BBB for rapid, unidirectional influx. The transport system does not require the entire EGF receptor and is susceptible to possible therapeutic manipulation...

..These findings imply the necessity of adjusting the dose of intravenously administered PACAP38 in order to maximize its therapeutic effect on the brain damage resulting from focal ischemia..

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..Our results show that peripherally administered LIF readily enters the brain and spinal cord by a saturable transport system across the BBB that may have biological implications...

..However, the regulatory elements and signaling pathways involved in this regulation are unknown...

..In the second table, the central nervous system effects are arranged alphabetically. No longer can there be any doubt that peptides affect the central nervous system, sometimes in several ways...

..These data infer that AP-2, along with previously reported Sp transcription factors, is involved in the up-regulation of Cx26 gene during pregnancy and lactation...

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..Thus, the gatekeeper function of the BBB can be expanded to a primary governing role, especially for entry of ingestive peptides subject to their respective saturable transport systems...

..Instead, these soluble receptors inhibited surface binding and endocytosis of leptin. Thus, we provide novel direct evidence both in vivo and in vitro that soluble receptors of leptin serve as antagonists of the transport of leptin...

..Still others, like interleukin-6, may reach the brain but are rapidly degraded. This review summarizes current knowledge and recent findings of the rapidly growing family of adipokines and their interactions with the BBB...

..This stability was further enhanced by inhibition of lysosomal activity. Thus, the intracellular pool of intact leptin may allow prolonged biological functions for this adipokine...

..The vesicular trafficking of TNFalpha reflects the immunomodulatory potential of peripheral cytokines for the CNS...

..We conclude that both CRHR1 and CRHR2 play a facilitatory role in the non-clathrin-, non-caveolae-mediated endocytosis and intracellular signal transduction of this potent peptide...

..With the co-existence of inflammation and hypoxia in the brain after ischemic stroke, dynamic changes of gammaGT activity reflect evolving changes of endothelial function...

..The amount of HGF that crossed the BBB in intact form was substantial and could be physiologically important in the CNS...

..Accordingly, we determined the differential role of the two receptors for tumor necrosis factor alpha (TNFR1, TNFR2) on cellular transcytosis...

..The novel opposite effects of proteasomes and lysosomes in controlling receptor expression shows the functional implications and interactions of circulating inflammatory cytokines in acutely modulating BBB activity...

..The results show that neuroinflammation by LPS induces endothelial signaling and enhances cytokine transport across the BBB...

..The results suggest that the BBB is an interface for blood-borne IL15 to interact with the CNS in the basal state and during inflammation...

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..The increased transport of TNF and LIF after SCI remains saturable and does not coincide with generalized BBB disruption, highlighting a pivotal regulatory role for the blood-spinal cord barrier...

..Overall, the developmental changes observed for leptin receptors unexpectedly failed to correlate with the entry of leptin into brain, and this may indicate different functions of the receptors in neonates and adults...

..Thus, urocortin endocytosis is a saturable process leading to vesicular intracellular transport that can be enhanced by cell-surface leptin...

..Many chemotherapeutic agents, anti-epileptics, anti-HIV drugs, and opiates are substrates for MDRs. Therefore, understanding the regulation of MDRs in the endothelial cells composing the blood-brain barrier has therapeutic implications...

..Thus, the limited penetration under physiological conditions does not limit the pharmacological delivery of this satiety peptide as a potential therapeutic agent...

..As we better understand how peripheral TNFalpha affects its own transport and modulates neuroregeneration, we may be in a better position to pharmacologically manipulate its regulatory transport system to treat stroke...

..The redundancy of their transport systems illustrates the regulatory function of the blood-brain barrier and reflects the importance of blood-borne insulin and IGF-I in the central nervous system...

..The differential interactions of obestatin, adiponectin, and ghrelin with the BBB illustrate their distinctive physiological interactions with the CNS...

..Better understanding of the nature and regulation of the transport systems at the BBB will provide a new direction to enhance the interactions of peripheral peptides and proteins with the CNS...

..Thus, sites of action of leptin, urocortin, and TNFalpha exist not only in the brain but also at the BBB where they each control the flow of other ingestive signals to CNS targets...

..This is the first time that some of them have been associated with TNF alpha signaling pathways...

..The results indicate that NRG-1-beta1 enters spinal cord and brain by a saturable receptor-mediated mechanism, which provides the opportunity for possible therapeutic manipulation at the BBB level...

..Thus, the therapeutic potential of TGF-beta1 administered in blood is probably limited to situations in which the BBB has been disrupted...

..Information from these studies could be useful in the design of analogues for delivery of PDGF as a therapeutic agent...

..We show that 125I-IL-10 is stable in circulating blood but does not cross the intact BBB after intravenous delivery. Thus, peripheral IL-10 probably can serve as a CNS therapeutic only when the BBB is disrupted...

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..Such a novel interaction between two peptides at the BBB opens new approaches for general study of the dynamic regulatory role of the BBB in brain-body communication as well as the specific study of obesity...

..Therefore, we conclude that [Ser8]GLP-1 and the endogenous peptide GLP-1 can gain access to the brain from the periphery by simple diffusion and thus contribute to the regulation of feeding...

..As endormorphins are mainly produced in the CNS, the presence of the efflux system at the BBB could play an important role in pain modulation and neuroendocrine control...

..These studies suggest that RAP may provide a novel means of protein-based drug delivery to the brain...

..This enhanced transport correlated with increased expression of LIFRalpha shown by immunofluorescent staining and Western blot. Therefore, LIFR at the BBB provides an important target for therapeutic intervention...

..Given the known multiple modulatory effects of TNFalpha after stroke, the results indicate that the TNFalpha transport system at the BBB facilitates neuroplasticity and plays an important role in stroke recovery...

..Thus, the differential uptake of AgRP by peripheral organs could be a regulated process that is modulated by food deprivation...

..The central nervous system effects of peripheral GH can be attributed to permeation of the BBB despite the absence of a specific transport system...

..Hopefully, hormesis will be routinely considered in the design of research projects and the discovery of pharmaceutical agents...

..By presenting in condensed form the effects of peptides which are essential for systems biology, we hope that this summary of existing knowledge will encourage additional novel research to be presented in Peptides...

..Mice with 4TCD(y) intrafemoral tumors showed increased effectiveness of radiation based on improved reductions in tumor size, reductions in tumorigenic osteolysis, and a decrease in skeletal fractures (P < 0.01)...

..Overall, insights arising from the experimental results may eventually lead to better therapeutic intervention so as to lessen the functional disability and enhance the quality of life in patients with SCI...

..Our results show that CINC, in contrast to MIP-2, is selectively transported from the lung to the systemic circulation, where it promotes neutrophil migration into the lung in response to a chemotactic stimulus...

..Efflux, which occurred at the same rate as the bulk reabsorption of cerebrospinal fluid, also was not saturable. In summary, FGF21 shows significant, non-saturable, unidirectional influx across the BBB...

..Thus, there are several therapeutic approaches to overcome the actions of endogenous neurite growth inhibitors so as to promote CNS regeneration...

..Thus, further understanding of the mechanisms of plasticity could lead to better ways of promoting useful reorganization and preventing undesirable consequences...

..By unexpectedly potentiating leptin signaling through Stat, urocortin amplifies the cellular response of leptin. This novel phenomenon suggests that urocortin can play an important compensatory role during leptin resistance in obesity...

..Thus, TNF stimulation results in decreased responsiveness of RBE4 cells to LIF, indicating complex regulatory interactions of cytokines at the BBB...

..6-kb C portion of the (TRAP) promoter, it is likely that transcription binding sites outside of the 2.2-kb region will have profound effects on regulation of the gene in vivo and in vitro...

..The results showing increased leptin permeation across the BBB lead to the speculation that leptin may serve as a homeostatic feeding signal in these mice...

..These peptides clearly illustrate that the name of a peptide restricts neither its actions nor its conceptual implications...