Cervical Lymph Nodes are Found in Direct Relationship With the Internal Carotid Artery: Significance for the Lymphatic Drainage of the Brain
Centre for Learning Anatomical Sciences, School of Medicine, University of Southampton, United Kingdom. Clinical Anatomy
(Impact Factor: 1.33).
01/2009; 23(1):43-7. DOI: 10.1002/ca.20887
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.
Available from: David H Cribbs
- "Perhaps surprisingly, plasma Aβ40 levels have recently been independently associated with small vessel disease , and these results are consistent with a role for Aβ40 in producing disruption of vascular endothelial function [89, 90]. Age-related alterations in transport across the blood–brain barrier, as well as a reduction in the efficacy of the perivascular drainage pathway, have been proposed to explain enhanced accumulation of cerebral parenchymal and vascular amyloid deposits in the elderly [91–95]. Modeling suggest that vessel pulsations provide the force to drive perivascular drainage, and age-related stiffening of arteries has been hypothesized to reduce flow and thus enhancing Aβ deposition in the central nervous system . "
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ABSTRACT: Stroke prevention efforts typically focus on either ischemic or hemorrhagic stroke. This approach is overly simplistic due to the frequent coexistence of ischemic and hemorrhagic cerebrovascular disease. This coexistence, termed "mixed cerebrovascular disease", offers a conceptual framework that appears useful for stroke prevention strategies. Mixed cerebrovascular disease incorporates clinical and subclinical syndromes, including ischemic stroke, subclinical infarct, white matter disease of aging (leukoaraiosis), intracerebral hemorrhage, and cerebral microbleeds. Reliance on mixed cerebrovascular disease as a diagnostic entity may assist in stratifying risk of hemorrhagic stroke associated with platelet therapy and anticoagulants. Animal models of hemorrhagic cerebrovascular disease, particularly models of cerebral amyloid angiopathy and hypertension, offer novel means for identifying underlying mechanisms and developing focused therapy. Phosphodiesterase (PDE) inhibitors represent a class of agents that, by targeting both platelets and vessel wall, provide the kind of dual actions necessary for stroke prevention, given the spectrum of disorders that characterizes mixed cerebrovascular disease.
Available from: PubMed Central
- "In CAA, Aβ is detected by immunohistochemistry mainly in the tunica media of smaller leptomeningeal arteries but is present in the adventitia on the outer aspects of medium-sized leptomeningeal arteries , suggesting that Aβ follows the same lymphatic drainage route as tracers in experimental animals [7,9]. Restriction of Aβ to the walls of intracranial arteries and its absence from the walls of the extracranial carotid artery  suggest that Aβ drains from the wall of the carotid artery to lymph nodes related to the artery at the base of the skull . The pattern of deposition of Aβ in the basement membranes of capillary and artery walls in CAA indicates that there is a failure of lymphatic drainage of Aβ and suggests that the failure is related to age changes in artery walls. "
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ABSTRACT: Amyloid is deposited in the walls of arteries and capillaries as cerebral amyloid angiopathy (CAA) in the brains of older individuals and of those with Alzheimer disease (AD). CAA in AD reflects an age-related failure of elimination of amyloid-beta (Abeta) from the brain along perivascular lymphatic drainage pathways. In the absence of conventional lymphatic vessel in the brain, interstitial fluid and solutes drain from the brain to cervical lymph nodes along narrow basement membranes in the walls of capillaries and arteries, a pathway that is largely separate from the cerebrospinal fluid. In this review we focus on the pathology and pathogenesis of CAA, its role in the aetiology of AD and its impact on immunotherapy for AD. The motive force for lymphatic drainage of the brain appears to be generated by arterial pulsations. Failure of elimination of Abeta along perivascular pathways coincides with a reduction in enzymic degradation of Abeta, reduced absorption of Abeta into the blood and age-related stiffening of artery walls that appears to reduce the motive force for lymphatic drainage. Reduced clearances of Abeta and CAA are associated with the accumulation of insoluble and soluble Abetas in the brain in AD and the probable loss of homeostasis of the neuronal environment due to retention of soluble metabolites within the brain. Tau metabolism may also be affected. Immunotherapy has been successful in removing insoluble plaques of Abeta from the brain in AD but with little effect on cognitive decline. One major problem is the increase in CAA in immunised patients that probably prevents the complete removal of Abeta from the brain. Increased knowledge of the physiology and structural and genetic aspects of the lymphatic drainage of Abeta from the brain will stimulate the development of therapeutic strategies for the prevention and treatment of AD.
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ABSTRACT: The amyloid cascade hypothesis of Alzheimer's disease (AD) is testable: it implies that interference with Abeta aggregation and plaque formation may be therapeutically useful. Abeta42 immunisation of amyloid precursor protein (APP) transgenic mice prevented plaque formation and caused removal of existing plaques. The first clinical studies of Abeta immunisation in AD patients (AN1792, Elan Pharmaceuticals) were halted when some patients suffered side effects. Since our confirmation that Abeta immunisation can prompt plaque removal in human AD, we have performed a clinical and neuropathological follow up of AD patients in the initial Elan Abeta immunisation trial. In immunised AD patients, we found: a lower Abeta load, with evidence that plaques had been removed; a reduced tau load in neuronal processes, but not in cell bodies; and no evidence of a beneficial effect on synapses. There were pathological "side effects" including: increased microglial activation; increased cerebral amyloid angiopathy; and there is some evidence for increased soluble/oligomeric Abeta. A pathophysiological mechanism involving effects on the cerebral vasculature is proposed for the clinical side effects observed with some active and passive vaccine protocols. Our current knowledge of the effects of Abeta immunotherapy is based on functional information from the early clinical trials and a few post mortem cases. Several further clinical studies are underway using a variety of protocols and important clinical, imaging and neuropathological data will become available in the near future. The information obtained will be important in helping to understand the pathogenesis not only of AD but also of other neurodegenerative disorders associated with protein aggregation.
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