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Abstract

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of beta-amyloid (A beta) peptides in the walls of arteries both in the cortex and meninges. Here, we test the hypothesis that CAA results from the progressive accumulation of A beta in the perivascular interstitial fluid drainage pathways of the brain. Experimental studies have shown that interstitial fluid (ISF) from the rat brain flows along periarterial spaces to join the cerebrospinal fluid (CSF) to drain to cervical lymph nodes. Such lymphatic drainage plays a key role in B-cell and T-cell mediated immunity of the brain. Anatomical studies have defined periarterial ISF drainage pathways in the human brain that are homologous with the lymphatic pathways in the rat brain but are largely separate from the CSF. Periarterial channels in the brain in man are in continuity with those of leptomeningeal arteries and can be traced from the brain to the extracranial portions of the internal carotid arteries related to deep cervical lymph nodes. The pattern of deposition of A beta in senile plaques and in CAA suggests that A beta accumulates in pericapillary and periarterial ISF drainage pathways. A beta could accumulate in CAA due to either (i) increased production of A beta, (ii) reduced solubility of A beta peptides, or (iii) impedance of drainage of A beta along periarterial ISF drainage pathways within the brain and leptomeninges due to aging factors in cerebral arteries. Elucidation of factors that reduce elimination of A beta via perivascular drainage pathways may lead to their rectification and to new strategies for treatment of Alzheimer's disease.

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CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance.

A Pantazis, R Weller, Adriana de S. B. Kida (1993)

Cerebrospinal fluid (CSF) drainage pathways from the rat brain were investigated by the injection of 50 microliters Indian ink into the cisterna magna. The distribution of the ink, as it escaped from the cranial CSF space, was documented in 2 mm thick slices of brain and skull cleared in cedar wood oil and in decalcified paraffin sections. Following injection of the ink, deep cervical lymph nodes were selectively blackened within 30 min and lumbar para-aortic nodes within 6 h. Within the cranial cavity, carbon particles accumulated in the basal cisterns but were also distributed in the paravascular spaces around the middle cerebral arteries and the nasal-olfactory artery. Carbon particles in the subarachnoid space beneath the olfactory bulbs drained directly into discrete channels which passed through the cribriform plate and into lymphatics in the nasal submucosa. Although ink was distributed along the subarachnoid space of the optic nerves and entered the cochlea, the nasal route was the only direct connection between cranial CSF and lymphatics. Arachnoid villi associated with superior and inferior sagittal sinuses were identified and a minor amount of drainage of ink into dural lymphatics was also observed. This study demonstrates the direct drainage of cerebrospinal fluid through the cribriform plate in anatomically defined channels which connect with the nasal lymphatics.(ABSTRACT TRUNCATED AT 250 WORDS)

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Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes.

H. POLLOCK, M. HUTCHINGS, R. O. WELLER … (1997)

There is evidence for lymphatic drainage of interstitial fluid from the brain along perivascular spaces in a number of mammalian species. Ultrastructural studies suggest that there are similar drainage pathways in the human cerebral cortex. Perivascular spaces in the basal ganglia, however, differ from those in the cortex in that they dilate to form lacunes and rarely accumulate beta-amyloid (amyloid angiopathy) in Alzheimer's disease; in the cortex, lacunes are rare but amyloid angiopathy is common. The aim of the present study is to compare the structure of perivascular spaces in the basal ganglia and at the anterior perforated substance with perivascular spaces in the cerebral cortex. Eight postmortem brains from patients aged 23-80 years (mean 68 y) were examined by light microscopy, by scanning and transmission electron microscopy and by direct visualisation of etched paraffin blocks. The results show that arteries in the basal ganglia are surrounded by 2 distinct coats of leptomeninges separated by a perivascular space which is continuous with the perivascular space around arteries in the subarachnoid space. The inner layer of leptomeninges closely invests the adventitia of the vessel wall and the outer layer is continuous with the pia mater on the surface of the brain at the anterior perforated substance. Veins in the basal ganglia have no outer layer of leptomeninges and thus the perivascular space is continuous with the subpial space. The anatomy of the periarterial spaces in the basal ganglia differs significantly from that in the cerebral cortex where there is only a single periarterial layer of leptomeninges. Differences in structure of perivascular spaces around arteries may reflect relative efficiencies in the drainage of interstitial fluid from different sites in the brain. Furthermore, the structure of the perivascular spaces may contribute to the relatively high frequency of lacunes in the basal ganglia, and the low frequency of amyloid angiopathy at this site in Alzheimer's disease.