Wang M, Ding F, Deng S, Guo X, Wang W, Iliff JJ, Nedergaard M. Focal Solute Trapping and Global Glymphatic Pathway Impairment in a Murine Model of Multiple Microinfarcts. J Neurosci. 2017 Mar 15;37(11):2870-2877. Epub 2017 Feb 10 PubMed.

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  1. In this study, Wang et al. created microinfarcts in the brain at three days after injection of cholesterol crystals into the carotid artery. Infarcts were identified by the presence of macrophages and reactive astrocytosis.

    Following injection of tracer into the CSF of the cisterna magna, influx of tracer alongside arteries into the surface of the brain was significantly reduced at 30 minutes after injection in the animals with multiple infarcts. Such impairment was greater in animals at 12 months of age compared with those at two to three months of age. Tracer accumulated within infarcts, presumably within macrophages, although this is not stated. No experiments examined the pathways of removal of tracer from the brain.

    This is a valuable new model of microinfarction, a common feature of small vessel disease, comparable to the models produced in recent years by the groups led by Murphy and Ihara (Silasi et al., 2015; Okamoto et al., 2012). Assessment of glymphatic/convective influx of the fluorescent tracer after 30 minutes of its injection into the CSF compartment showed the tracer in association with the perivascular compartment of arteries, suggesting that solutes that enter the brain from the CSF along the pial-glial basement membranes, are then directed toward the intramural periarterial drainage pathways. Cholesterol crystals occluding cerebral arteries as well as the age-related arterial stiffness appear to interfere with the motive force for both glymphatic entry of CSF and intramural periarterial drainage.

    The discussion is rather speculative, and citation of the literature concerned with entry and elimination of fluid and solutes into and from the brain is selective and restricted. It is not clear how the results of this paper can be translated into the development of treatments for multi-infarct dementia or other dementias.

    References:

    Silasi G, She J, Boyd JD, Xue S, Murphy TH. A mouse model of small-vessel disease that produces brain-wide-identified microocclusions and regionally selective neuronal injury. J Cereb Blood Flow Metab. 2015 May;35(5):734-8. Epub 2015 Feb 18 PubMed.

    Okamoto Y, Yamamoto T, Kalaria RN, Senzaki H, Maki T, Hase Y, Kitamura A, Washida K, Yamada M, Ito H, Tomimoto H, Takahashi R, Ihara M. Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol. 2012 Mar;123(3):381-94. Epub 2011 Dec 15 PubMed.

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