Anatomical pathways for lymphatic drainage of the brain and their pathological significance

Kida, Shinya; Weller, Roy O.; Zhang, E T; Phillips, Marian J.; Iannotti, Fausto

doi:10.1111/j.1365-2990.1995.tb01048.x

Cited by 63 publications

(37 citation statements)

References 13 publications

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“…In other organs, such as the lung or stomach, there are well-defined thin-walled lymphatic vessels along which interstitial fluid, solutes, and inflammatory cells drain to regional lymph nodes (Casley-Smith, 1968). Although there are no true lymphatics in the brain, studies in experimental animals have shown that solutes injected into the brain drain to lymph nodes in the neck (Cserr et al, , 1992bIchimura et al, 1991;Zhang et al, 1992;Kida et al, 1995;Knopf et al, 1995). When a soluble fluorescent tracer is injected into the grey matter of the brain, it initially spreads diffusely through the narrow extracellular spaces and rapidly enters capillary and artery walls to drain out of the brain .…”

Section: Introductionmentioning

confidence: 99%

Cervical lymph nodes are found in direct relationship with the internal carotid artery: Significance for the lymphatic drainage of the brain

et al. 2009

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The brain has no conventional lymphatics, but solutes injected into it drain along artery walls and reach lymph nodes in the neck. This study seeks to identify cervical lymph nodes related to the human internal carotid artery (ICA) that could act as the first regional lymph nodes for the brain. Bilateral dissections were carried out on four embalmed human heads, from the level of the carotid bifurcation in the neck, to the base of the skull. Lymph nodes from every specimen were processed for histological examination. A total of 51 deep cervical lymph nodes were identified: 12 lymph nodes (confirmed by histological examination) were observed to be in direct relationship with the ICA. These lymph nodes were found within the carotid sheath and had average diameters of 13.5 x 4.8 mm. Solutes and interstitial fluid from the brain may drain along the walls of cerebral arteries and reach these lymph nodes. They may be sites of stimulation of immune responses against antigens from the brain.

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Section: Introductionmentioning

confidence: 99%

Cervical lymph nodes are found in direct relationship with the internal carotid artery: Significance for the lymphatic drainage of the brain

et al. 2009

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“…Although the CNS has often been described as an immunologically privileged site (5,6), recent studies by our group and others have shown that peripheral vaccinations can induce effective anti-CNS tumor immune responses (7)(8)(9)(10)(11)(12). Based on our previous results using peripheral vaccination with syngeneic glioma cells that had been genetically engineered to secrete IL-4 (8, 9, 13), we have initiated a clinical trial using autologous glioma cells as a vaccine (10,14,15).…”

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confidence: 99%

Delivery of Dendritic Cells Engineered to Secrete IFN-α into Central Nervous System Tumors Enhances the Efficacy of Peripheral Tumor Cell Vaccines: Dependence on Apoptotic Pathways

Kuwashima

Nishimura

Eguchi

et al. 2005

The Journal of Immunology

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We tested whether modulation of the CNS-tumor microenvironment by delivery of IFN-α-transduced dendritic cells (DCs: DC-IFN-α) would enhance the therapeutic efficacy of peripheral vaccinations with cytokine-gene transduced tumor cells. Mice bearing intracranial GL261 glioma or MCA205 sarcoma received peripheral immunizations with corresponding irradiated tumor cells engineered to express IL-4 or GM-CSFs, respectively, as well as intratumoral delivery of DC-IFN-α. This regimen prolonged survival of the animals and induced tumor-specific CTLs that expressed TRAIL, which in concert with perforin and Fas ligand (FasL) was involved in the tumor-specific CTL activity of these cells. The in vivo antitumor activity associated with this approach was abrogated by administration of neutralizing mAbs against TRAIL or FasL and was not observed in perforin−/−, IFN-γ−/−, or FasL−/− mice. Transduction of the tumor cells with antiapoptotic protein cellular FLIP rendered the gene-modified cells resistant to TRAIL- or FasL-mediated apoptosis and to CTL killing activity in vitro. Furthermore, the combination therapeutic regimen was ineffective in an intracranial cellular FLIP-transduced MCA205 brain tumor model. These results suggest that the combination of intratumoral delivery of DC-IFN-α and peripheral immunization with cytokine-gene transduced tumor cells may be an effective therapy for brain tumors that are sensitive to apoptotic signaling pathways.

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“…Such leukocyte trafficking could serve both as a means of viral spread as well as an attempt to elicit cellular immune responses to destroy infected MP. Certainly, several pathways are operative by which lymphocytes may reach the brain (24,25). Circulating lymphocytes from periphery to brain and vice versa may deliver virus to regional lymph nodes as well as distant lymphoid tissues where uninfected T lymphocytes circulate (26).…”

Section: Discussionmentioning

confidence: 99%

Generation of Cytotoxic T Cells Against Virus-Infected Human Brain Macrophages in a Murine Model of HIV-1 Encephalitis

Poluektova¹,

Munn

Persidsky³

et al. 2002

The Journal of Immunology

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HIV-1 encephalitis (HIVE) and its associated dementia can occur in up to 20% of infected individuals, usually when productive viral replication in brain mononuclear phagocytes (macrophages and microglia) and depletion of CD4+ T lymphocytes are most significant. T cells control viral replication through much of HIV-1 disease, but how this occurs remains incompletely understood. With this in mind, we studied HIV-1-specific CTL responses in a nonobese diabetic (NOD)-SCID mouse model of HIVE. HIV-1-infected monocyte-derived macrophages (MDM) were injected into the basal ganglia after syngeneic immune reconstitution by HLA-A*0201-positive human PBL to generate a human PBL-NOD-SCID HIVE mouse. Engrafted T lymphocytes produced HIV-1gag- and HIV-1pol-specific CTL against virus-infected brain MDM within 7 days. This was demonstrated by tetramer staining of human PBL in mouse spleens and by IFN-γ ELISPOT. CD8, granzyme B, HLA-DR, and CD45R0 Ag-reactive T cells and CD79α-positive B cells migrated to and were in contact with human MDM in brain areas where infected macrophages were abundant. The numbers of productively infected MDM were markedly reduced (>85%) during 2 wk of observation. The human PBL-NOD-SCID HIVE mouse provides a new tool for studies of cellular immune responses against HIV-1-infected brain mononuclear phagocytes during natural disease and after vaccination.

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Anatomical pathways for lymphatic drainage of the brain and their pathological significance

Cited by 63 publications

References 13 publications

Cervical lymph nodes are found in direct relationship with the internal carotid artery: Significance for the lymphatic drainage of the brain

Cervical lymph nodes are found in direct relationship with the internal carotid artery: Significance for the lymphatic drainage of the brain

Delivery of Dendritic Cells Engineered to Secrete IFN-α into Central Nervous System Tumors Enhances the Efficacy of Peripheral Tumor Cell Vaccines: Dependence on Apoptotic Pathways

Generation of Cytotoxic T Cells Against Virus-Infected Human Brain Macrophages in a Murine Model of HIV-1 Encephalitis

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