. New neurons follow the flow of cerebrospinal fluid in the adult brain. Science. 2006 Feb 3;311(5761):629-32. PubMed.

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  1. In this paper, the authors track the migration of neuroblasts from the subventricular zone in adult mice and show that they are propelled rostrally within the CSF of the lateral ventricles by directional movement of cilia on ependymal cells and by concentration gradients of guidance molecules produced by the choroid plexus. This well-performed and rather ingenious study has implications for the possible migration of therapeutically implanted stem cells in neurodegenerative disease and for the general approach to communication within the CNS.

    Although the most prominent communication system in the CNS involves one-to-one direct connections between neurons, there are also the all-important communication systems based on fluid flow or diffusion. Beyond the blood-brain barrier, interstitial fluid and solutes first diffuse between cell processes [1,2] and second, travel out of the brain by bulk flow along capillary and artery basement membranes [2,3]. Both these communication systems are disrupted in Alzheimer disease by the deposition of amyloid-β either as plaques in the brain parenchyma [4,5] or in vessel walls as cerebral amyloid angiopathy [6,7]. The third fluid system is CSF, and this is separated to some extent from interstitial fluid and perivascular drainage pathways in the human brain by leptomeninges [8]. Motive forces for the circulation of CSF and for the drainage of ISF appear to be derived from pulsations in blood vessels [9,10].

    However, from the paper by Sawamoto et al., it is clear that the actions of cilia and chemo-attractants (or in this case “chemo-distractants”) play important roles in the migration of cells in the CSF of the ventricles. It will be interesting to see whether these mechanisms can be exploited to enhance the delivery of cells to the brain via the CSF by invasive or non-invasive routes [11].

    References:

    . Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol Sci. 1999 Apr;20(4):142-50. PubMed.

    . Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int. 2004 Sep;45(4):545-52. PubMed.

    . Perivascular pathways for the clearance of interstitial fluid from the brain and the pathology of Alzheimer's disease. Neuropathol Appl Neurobiol 2005;31(2):218.

    . Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis. Eur J Neurosci. 2004 Aug;20(3):811-7. PubMed.

    . Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. Am J Pathol. 1998 Sep;153(3):725-33. PubMed.

    . Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol. 2003 Apr;29(2):106-17. PubMed.

    . Microscopic morphology and histology of the human meninges. Morphologie. 2005 Mar;89(284):22-34. PubMed.

    . MR-Intracranial pressure (ICP): a method to measure intracranial elastance and pressure noninvasively by means of MR imaging: baboon and human study. Radiology. 2000 Dec;217(3):877-85. PubMed.

    . Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol. 2006 Feb 21;238(4):962-74. PubMed.

    . Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience. 2004;127(2):481-96. PubMed.

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