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      Time Course of Hyperosmolar Opening of the Blood-Brain and Blood-CSF Barriers in Spontaneously Hypertensive Rats

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          The time course of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) responses to hyperosmolar mannitol infusion (HMI; 1.6 M) during chronic hypertension was investigated using <sup>14</sup>C-sucrose as a marker of barrier integrity. <sup>14</sup>C-sucrose entry into CSF of both spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats 2 min after HMI increased ∼7-fold compared to their respective control. The volume of distribution (V<sub>d</sub>) of <sup>14</sup>C-sucrose into brain cortex of SHR increased 13-fold 2 min after HMI while that in WKY rats increased only 4-fold. After HMI V<sub>d</sub> of <sup>14</sup>C-sucrose into the cortex of WKY, and CSF of both SHR and WKY remained steadily greater than their corresponding control for up to 30 min (p < 0.01), whereas in the cortex of SHR the V<sub>d</sub> of <sup>14</sup>C-sucrose reached control values 20 min after HMI (p > 0.05), indicating that after HMI the increase in paracellular diffusion of <sup>14</sup>C-sucrose into SHR cortex was not persistent, in contrast to WKY rats and CSF of both SHR and WKY rats. Electron microscopy of the brain cortex after HMI showed capillary endothelial cell shrinkage and perivascular swellings in the brain cortex, and in the choroid plexus opening of tight junctions were observed. Our results indicate disruption of both the BBB and the BCSFB after HMI in both SHR and WKY rats. The disruption remained persistent up to 25 min after HMI at the BBB of WKY rats and BCSFB in both animal groups, while in SHR the protective function of the BBB returned to control values 20 min after HMI.

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          Most cited references 30

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          Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means.

           E Neuwelt,  R Kroll (1998)
          This article reviews historical aspects of the blood-brain barrier (BBB) and recent advances in mechanisms to deliver therapeutic agents across the BBB for the treatment of intracerebral tumors and other neurological diseases. The development of the osmotic BBB disruption procedure as a clinically useful technique is described. Osmotic BBB disruption is contrasted with alternative methods for opening or bypassing the BBB, including pharmacological modification of the BBB with bradykinin and direct intracerebral infusion. Laboratory studies have played a fundamental role in advancing our understanding of the BBB and delivery of agents to brain. Preclinical animal studies will continue to serve an integral function in our efforts to improve the diagnosis and treatment of a number of neurological disorders. Techniques involving the modification of the BBB and/or blood-tumor barrier to increase delivery of therapeutic agents have been advanced to clinical trials in patients with brain tumors with very favorable results. Improving delivery of agents to the brain will play a major role in the therapeutic outcome of brain neoplasms. As techniques for gene therapy are advanced, manipulation of the BBB also may be important in the treatment of central nervous system genetic disorders.
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            The ependyma: a protective barrier between brain and cerebrospinal fluid.

            This review summarizes the current scientific literature concerning the ependymal lining of the cerebral ventricles of the brain with an emphasis on selective barrier function and protective roles for the common ependymal cell. Topics covered include the development, morphology, protein and enzyme expression including reactive changes, and pathology. Some cells lining the neural tube are committed at an early stage to becoming ependymal cells. They serve a secretory function and perhaps act as a cellular/axonal guidance system, particularly during fetal development. In the mature mammalian brain ependymal cells possess the structural and enzymatic characteristics necessary for scavenging and detoxifying a wide variety of substances in the CSF, thus forming a metabolic barrier at the brain-CSF interface.
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              The structure of the choroid plexus and the physiology of the choroid plexus epithelium.

               B. Segal,  Z Redzic (2004)
              The choroid plexuses (CPs) are leaf-like highly vascular structures laying in the ventricles. The main function of choroid plexuses is the production of the cerebrospinal fluid (CSF). Although CPs have a unique distribution of ion transporters/channels, the mechanism of CSF production is similar to the production of fluids in other epithelia and is based on energy released from ATP hydrolysis, which drives unidirectional flux of ions accompanied by movement of water by osmosis. The CPs have an important role in the homeostasis of nutrients in the CSF since the kinetic parameters of glucose and amino acid (AA) transport across the CPs are the main reason for the low concentration of these molecules in the CSF. The CPs appear to be source of CSF-borne hormones and growth factors, including insulin-like growth factor II (IGF II), vasopressin (VP) and transforming growth factor beta1 (TGF-beta1). The CPs also synthesise the thyroid transporting protein transthyretin and transferrin and can chelate heavy metals.

                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                February 2007
                28 December 2006
                : 44
                : 2
                : 99-109
                aDepartment of Physiology, Faculty of Medicine, and bDepartment of Biological Sciences, Faculty of Science, Kuwait University, Safat, Kuwait
                98260 J Vasc Res 2007;44:99–109
                © 2007 S. Karger AG, Basel

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                Page count
                Figures: 7, References: 42, Pages: 11
                Research Paper


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