Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain

1] Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642 [2] Letten Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway [3] Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway [4].
Scientific Reports (Impact Factor: 5.58). 09/2013; 3:2582. DOI: 10.1038/srep02582
Source: PubMed


In the brain, a paravascular space exists between vascular cells and astroglial end-foot processes, creating a continuous sheath surrounding blood vessels. Using in vivo two-photon imaging we demonstrate that the paravascular circulation facilitates selective transport of small lipophilic molecules, rapid interstitial fluid movement and widespread glial calcium signaling. Depressurizing the paravascular system leads to unselective lipid diffusion, intracellular lipid accumulation and pathological signaling in astrocytes. As the central nervous system is devoid of lymphatic vessels, the paravascular space may serve as a lymphatic equivalent that represents a separate highway for the transport of lipids and signaling molecules.

Download full-text


Available from: Benjamin A Plog, Oct 13, 2014
  • Source
    • "Although the exact functional relationship between the infusion of CSF into brain tissue and lymphatic drainage of ISF is at the moment unclear, the relationships could change with age and other factors that influence interstitial fluid drainage, like expression of aquaporins that control the transit of water across the astrocyte end-feet (Nedergaard, 2013). Recent data suggest that the pathways of entry of lipophilic and hydrophilic tracers from the CSF into the brain parenchyma are similar and involve penetrating arteries and veins (Rangroo Thrane et al., 2013). Elimination of solutes from brain parenchyma into the CSF may be a pathway that compensates for blockage of interstitial fluid drainage in AD but interstitial fluid drainage does not seem to compensate for blockage of CSF drainage as in hydrocephalus. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Immunological privilege appears to be a product of unique lymphatic drainage systems for the brain and receptor-mediated entry of inflammatory cells through the blood-brain barrier. Most organs of the body have well-defined lymphatic vessels that carry extracellular fluid, antigen presenting cells, lymphocytes, neoplastic cells and even bacteria to regional lymph nodes. The brain has no such conventional lymphatics, but has perivascular pathways that drain interstitial fluid (ISF) from brain parenchyma and cerebrospinal fluid (CSF) from the subarachnoid space to cervical lymph nodes. ISF and solutes drain along narrow, ∼100 nm-thick basement membranes within the walls of cerebral capillaries and arteries to cervical lymph nodes; this pathway does not allow traffic of lymphocytes or antigen presenting cells from brain to lymph nodes. Although CSF drains into blood through arachnoid villi, CSF also drains from the subarachnoid space through channels in the cribriform plate of the ethmoid bone into nasal lymphatics and thence to cervical lymph nodes. This pathway does allow the traffic of lymphocytes and antigen presenting cells from CSF to cervical lymph nodes. Efferent pathways by which lymphocytes enter the brain are regulated by selected integrins on lymphocytes and selective receptors on vascular endothelial cells. Here we review (1) the structure and function of afferent lymphatic drainage of ISF and CSF (2) mechanisms involved in the efferent pathways by which lymphocytes enter the brain (3) the failure of lymphatic drainage of the brain parenchyma with age and the role of such failure in the pathogenesis of Alzheimer's disease.
    Brain Behavior and Immunity 10/2013; 36. DOI:10.1016/j.bbi.2013.10.012 · 5.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A better understanding of volume transmission is important in neuropsychiatry, as this is now believed to be a major mode of action for many neuroactive substances, including the modulatory neurotransmitters and many psychiatric medications.1,17-19 The original conceptualization of information transfer in the central nervous system (CNS) was that it depended entirely on synaptic transmission. Although the point-to-point (wired) communication provided by synaptic transmission still receives most of the attention, there is growing evidence of the importance of other mechanisms, particularly extrasynaptic volume transmission. Volume transmission functions quite differently from synaptic (wired) transmission, which is optimized for communication that is high-speed and precise. In contrast, volume transmission provides a communication mode that is temporally slower and anatomically broader in reach, and more suited to modulatory and tuning functions.
    The Journal of Neuropsychiatry and Clinical Neurosciences 02/2014; 26(1):iv-4. DOI:10.1176/appi.neuropsych.13110351 · 2.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A promising, safe, and economic fluorescent probe, g-C3N4 single-layered QDs, is introduced for two-photon fluorescence imaging of the cellular nucleus for the first time. The large two-photon absorption cross section, the high photostability, good biocompatibility and non-toxicity, negligible photothermal effect, and specific interaction with DNA render the single-layered g-C3N4 QDs as a promising candidate for in vivo and in vitro two-photon fluorescence imaging and further biomedical applications.
    Advanced Materials 07/2014; 26(26). DOI:10.1002/adma.201400111 · 17.49 Impact Factor
Show more