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Cerebral Arteriopathies due to Failure of Lymphatic Drainage and Protein Elimination

Year 2013, Volume: 5 Issue: 3, 32 - 40, 01.12.2013

Abstract

Aim: In most organs of the body, lymphatic drainage involves the drainage of solutes, antigens, antigen presenting cells and tissue debris along the defined lymphatic channels to the regional lymph nodes. The Central Nervous System CNS is considered to be an immunologically privileged organ without conventional lymphatic system and lymphatic drainage. Although there are no conventional lymphatic pathways in the brain, physiological studies revealed a substantial and immunologically significant lymphatic drainage from brain to cervical lymph nodes in humans. Methods: Disturbance of the perivascular drainage of fluids and solutes abnormal- garbage proteins from the brain parenchyma is called as Protein Elimination Failure Arteriopathies PEFA . Those protein deposits are associated with the pathophysiology of these diseases and include Cerebral Amyloid Angiopathy CAA , Alzheimer's Disease AD , Cruzfeld-Jacobs Disease CJD , Parkinson's Disease, Chronic Traumatic Encephalomyopathy CTE , Results: According to our opinion PEFA is a disease characterized by the failure of elimination of toxic, degenerated and possibly used garbage abnormal proteins from the extracellular milieu. In lights of this new idea about how abnormally folded versions of these proteins may be toxic and lead to disease, our findings are yielding insights into the disease pathogenesis but may also provide some new therapeutic insights. Conclusion: In this review we survey the evidences for the flow of brain interstitial fluid ISF via the preferential pathways through the brain, its relation to cerebrospinal fluid CSF and the results of the blockage of lymphatic drainage form the brain parenchyma.

References

  • Williams PL (ed) Gray’s Anatomy, 38th ed. Livin- gstone, Edinburgh. Churchill. 1995.
  • Galea I, Bechmann I, Perry VH. What is immune privilege (not)? Trend Immunol. 2007; 28: 12-18.
  • Weller RO, Djuanda E, Yow HY, et al. Lymphatic drainage of the brain and the pathophysio- logy of neurological disease. Acta Neuropathol. 2009;1171-14.
  • Weller RO, Galea I, Carare RO, et al. Pathophysi- ology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis. Pathophysio- logy. 2010;17: 295-306.
  • Weller RO, Massey A, Newman TA, et al. Cerebral amyloid angiopathy: amyloid beta accumulate- sin putative interstitial fluid drainage pathways in Alzheimer’s disease. Am J Pathol. 1998;58: 348-350.
  • Weller RO Subash M, Preston SD, et al. Perivascu- lar drainage of amyloid-β peptides from the bra- in and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol. 2008;18: 253-266.
  • Salzman KL, Osborn AG, House P, et al. Giant tu- mefactive perivascular space. Am J neuroradiol. 2005; 26 :298-305.
  • Abbott NJ. (2004) Evidence for bulk flow of brain interstitial fluid: significance of physiology and pathology. Neurochem Int. 2004; 45:545-552.
  • Szentistvanyi I, Patlak CS, Wllis RA, et al. Drainage of interstitial fluid from different regions of rat bra- in. Am J Physiol. 1984;264:F835-F844.
  • Cserr HF, Knopf PM. Cervical lymphatics, the blo- od-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992;13: 507- 512.
  • Schley D, Carare-Nnadi R, Please CP, et al. Mechanis- ms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol. 2006;238:962- 974.
  • 1Beach TG, Potter PE, Kuo YM, et al. Cholinergic deafferentiation of the rabbit cortex: anew ani- mal model of A beta deposition. Neurosci Lett. 2000;283:9-12.
  • Clapham R, O’Sullivan E, Weller RO, et al. Cervical lymph nodes are found in direct relationship with the internal carotid artery: significance for the lym- phatic drainage of the brain. Clin Anat. 2010; 23:43- 47.
  • Killer HE, Laeng HR, Groscurth P. Lymphatic capil- laries in the meninges of the human optic nerve. J Neuroophhalmol. 1999;19: 222-228.
  • Killer HE, Jaggi GP, Flammer J, et al. Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional? Brain 2007;130:514-520.
  • Del Bigio MR, Enno TL. Effect of hydrocephalus on rat brain extracellular compartment. Cerebrospinal Fluid Res. 2008;5: 12.
  • Alcolado R, Weller RO, Parrish EP, et al. The cranial arachnoid and pia mater in man. Anatomical and ultrastructural observations. Neuropathol Appl Neurobiol. 1988; 14:1-17.
  • Krahn V. Leukodiapedesis and leukocyte migrati- on in the leptomeninges and in the subarachnoid space. J Neurol. 1981;226: 43-52.
  • Nicholas DS, Weller RO. The fine anatomy of the human spinal meninges A light and scanning ele- ctron microscopy study. J Neurosurg. 1988;69: 276- 282.
  • Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain-barrier disorder in Alzheimer’s di- sease. Acta Neuropathol. 2009;118:103-113.
  • Preston SD, Sterart PV, Wilkinson A, et al. Capillary and arterial cerebral amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol. 2003;29:106-117.
  • Zhang ET, Inman CB, Weller RO. Interrelations- hips of the pia mater and the perivascular (Vir- chow-Robin) spaces in the human cerebrum. J Anat. 1990;170:111-123.
  • Kida S, Steart PV, Zhang ET, et al. Perivascular cells act as scavengers in the cerebral perivas- cular spaces and remain distinct from pericytes, microglia and macrophages. Acta Neuropathol. 1993;85: 646-652.
  • Chow N, Bell RD, Deane R, et al. Serum response factor and myocardin mediate arterial hyper- contractility and cerebral blood flow dysregula- tion in Alzheimer’s phenotype. Proc Natl Acad Sci USA 2007;104: 823-828.
  • McKee AC, Gavett BE, Stern RA, et al. TDP-43 proteinopathy and motor neuron disease in ch- ronic traumatic encephalopathy. J Neuropathol Exp Neurol. 2010;69918-929.
  • Gomez-Ramos A, Diaz-Hernandez M, Cuadros R, et al. Extracellular tau is toxic to neuronal cells. FEBS Lett. 2006;580:4842-4850.
  • Gomez-Ramos A, Diaz-Hernandez M, Rubio A, et al. Extracellular tau promotes intracellular cal- cium increase through M1 and M3 muscarinic receptors in neuronal cells. Mol Cell Neuroscı. 2008;37: 673-681.
  • Price DL, Borchelt DR, Sisodia SS. Alzheimer’s disease and the prion disorders amyloid β- pro- tein and prion protein amyloidoses. Proc Natl Acad Sci USA. 1993;90: 6381-6384.
  • Schubert D, Jin L-W, Saitoh T, et al. The regulati- on of amyloid β protein precursor secretion and its modulatory role in cell adhesion. Neuron. 1989;3: 689-694.
  • Saitoh T, Sundsmo M, Roch J-M, et al. Secreted form of Amyloid β protein precursor is invol- ved in the growth regulation of fibroblasts Cell 1989;58: 615-622.
  • Klier FG, Cole G, Stalleup W, et al. Amyloid β-pro- tein precursor is associated with extracellular matrix. Brain Res 1990;515:336-342.
  • Nishimoto I, Okamoto T, Matsuura Y, et al. Alzhe- imer amyloid protein precursor complexes with brain GTP-binding protein Go. Nature 1993; 362: 75-79.
  • Shoji M, Golde T, Glisso J, et al. Production of the Alzheimer amyloid beta protein by normal proteo- lytic processing. Science 1992;258:126-129.
  • Seubert P, Vigo-Pelfrey C, Esch F, et al. Isolation and quantification of soluble Alzheimer’s beta-pepe- tide from biological fluids. Nature. 1992;359:325- 327.
  • Kanekiyo T, Ban T, Aritake K, et al. Lipocalin-type prostaglandin D synthase (β-trace) is a major amy- loid β-chaperone in human cerebrospinal fluid. PNAS. 2007;104:6412-6417.
  • Walsh DM, Selkoe DJ. Abeta oligomers- adecade of discovery. J Neurochem. 2007;101: 1172-1184.
  • Herzig MC, Winkler DT, Burgermeister P, et al. Aβ is targeted to the vasculature in a mouse model of cerebral hereditary hemorrhage with amyloidosis. Nat Neurosci. 2004;7: 954-960.
  • Revesz T, Ghiso J, Lashley T, et al. Cerebral amylo- id angiopathies: a pathologic, biochemical , and genetic view. J Neuropathol Exp Neurol. 2003;62: 885-898.
  • Rostagno A, Ghiso J. Preamyloid lesions and ce- rebrovascular deposits in the mechanism of de- mentia: Lessons from Non-β-Amyloid cerebral Amyloidosis. Neurodegenerative Diseases. 2008;5: 173-175.
  • Hardy J, Cullen K. Amyloid at the blood vessel wall. Nat Med. 2006;12: 756-757.
  • Mahley RW, Weisgraber KH, Huang Y. Apolipopro- tein E4: causative factor and therapeutic target in neuropathology including Alzheimer’s disease. PNAS 2006;103:5644-5651.
  • Buee L, Bussiere T, Buee-Scherrer V, et al. Tau pro- tein isoforms, phosphorylation and role in neuro- degenerative disorders. Brain Res rev 2000;33: 95- 130.
  • Leger JG, Brandt R, Lee G. Identification of tau pro- tein regions required for process formation in PC12 cells. J Cell Sci. 1994;107:3403-3412.
  • Alonso AD, Zaidi T, Novak M, et al. Interactions of tau isoforms with Alzheimer’s disease abnormally hyperphosphorylated tau and invitro phosphory- lation into the disease-like protein. J Biol Chem. 2001;276:37967-37973.
  • Trojanowski JQ, Lee VM. The role of tau in Alzhe- imer’s disease. Med Clin North Am. 2002; 86:615- 627.
  • Feijoo C, Campbell DG, Jakes R, et al. Evidence that phosphorylation of the microtubule-asso- ciated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly. J Cell Sci. 2005;118:397-408.
  • Drewes G. MARKing tau for tangles and toxicity. Trends Biochem Sci. 2004;29548-55. Review.
  • Avila J. Intracellular and extracellular tau. Fron- tiers in Neuroscience. 2010;4: 1-4.
  • Frost B, Diamond MI. The expanding realm of pri- on phenomena in neurodegenerative disease. Prion. 2009;3: 74-77.
  • Isaacs JD, Jackson GS, Altmann DM. The role of the cellular prion protein in the immune sys- tem. Clinical and Experimental Immunology. 2006;146:1-8.
  • Carare RO, Bernardes-Silva M, Newman TA, et al. Solutes but not cells, drain from the brain paren- chyma along basement membranes of capilla- ries and arteries. Significance of cerebral amyloid angiopathy and neuroimmunology. Neuropat- hol Appl Neurobiology. 2008; 34:131-144.
  • Sisoda SS, Price DL. Role of the β-amyloid protein in Alzheimer’s disease. FASEB J. 1995;9: 366-370.

Beyinin Lenfatik Drenaj ve Protein Eliminasyon Yetmezliğine Bağlı Arteriyopatileri

Year 2013, Volume: 5 Issue: 3, 32 - 40, 01.12.2013

Abstract

Amaç: Vücuttaki birçok organda lenfatik drenaj, tanımlı lenfatik kanallardan bölgesel lenf nodlarına kadar olan uzanım boyunca çözünmüş maddeleri, antijenleri, antijen sunucu hücreleri ve yıkılmış doku parçalarını içerir. Santral Sinir Sistemi'nin SSS ise, konvansiyonel lenfatik sisteme ve lenfatik drenaja sahip olmadığı, immünolojik açıdan özel bir konuma sahip olduğu düşünülür. Beynin içinde konvansiyonel lenfatik yolaklar olmamasına karşın, fizyolojik çalışmalar insanda beyinden servikal lenf nodlarına kadar zengin ve immünolojik açıdan önemli bir lenfatik drenajın varlığını ortaya koymuştur. Metod: Beyin parankiminden sıvıların ve yıkılan parçaların anormal-artık proteinler perivasküler drenajındaki bozukluklar Protein Eliminasyon Yetmezliği Arteriyopatileri PEYA olarak isimlendirilmektedir. Bu tip bozukluklarda meydana gelen protein birikimleri, Serebral Amiloid Anjiyopati SAA , Alzheimer Hastalığı AH , Crutzfeld-Jacobs Hastalığı CJH , Parkinson Hastalığı PH , Kronik Travmatik Ensefalomiyopati KTE , Frontotemporal Demans FTD , Sporadik Amiyotrofik Lateral Skleroz SALS gibi proteinopatileri kapsayan hastalıkların patofizyolojileriyle ilişkilidirler. Bulgular: Bizim düşüncemize gore, PEYA toksik, dejenere olmuş, olasılıkla kullanılmış, artık anormal proteinlerin ekstrasellüler ortamdan eliminasyonundaki yetersizlik ile karakterize bir hastalıktır. Bu proteinlerin anormal bir şekilde katlanmış olan çeşitlerinin nasıl toksik hale gelebildikleri ve hastalığa yol açtıkları ile ilgili bu yeni görüşler, hastalığın patogenezi ile ilgili yeni anlayışlar getirmekte ve ayrıca yeni bazı tedavi olanakları için de imkân sunmaktadır. Sonuç: Bu derlemede biz, beyin interstisyel sıvısının İSS beyinde öncelikli yolaklar boyunca akışı, beyin omurilik sıvısı BOS ile ilişkisi ve beyin parankiminden lenfatik drenajın blokajının sonuçlarıyla ilgili bulguları gözden geçirmekteyiz.

References

  • Williams PL (ed) Gray’s Anatomy, 38th ed. Livin- gstone, Edinburgh. Churchill. 1995.
  • Galea I, Bechmann I, Perry VH. What is immune privilege (not)? Trend Immunol. 2007; 28: 12-18.
  • Weller RO, Djuanda E, Yow HY, et al. Lymphatic drainage of the brain and the pathophysio- logy of neurological disease. Acta Neuropathol. 2009;1171-14.
  • Weller RO, Galea I, Carare RO, et al. Pathophysi- ology of the lymphatic drainage of the central nervous system: implications for pathogenesis and therapy of multiple sclerosis. Pathophysio- logy. 2010;17: 295-306.
  • Weller RO, Massey A, Newman TA, et al. Cerebral amyloid angiopathy: amyloid beta accumulate- sin putative interstitial fluid drainage pathways in Alzheimer’s disease. Am J Pathol. 1998;58: 348-350.
  • Weller RO Subash M, Preston SD, et al. Perivascu- lar drainage of amyloid-β peptides from the bra- in and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol. 2008;18: 253-266.
  • Salzman KL, Osborn AG, House P, et al. Giant tu- mefactive perivascular space. Am J neuroradiol. 2005; 26 :298-305.
  • Abbott NJ. (2004) Evidence for bulk flow of brain interstitial fluid: significance of physiology and pathology. Neurochem Int. 2004; 45:545-552.
  • Szentistvanyi I, Patlak CS, Wllis RA, et al. Drainage of interstitial fluid from different regions of rat bra- in. Am J Physiol. 1984;264:F835-F844.
  • Cserr HF, Knopf PM. Cervical lymphatics, the blo- od-brain barrier and the immunoreactivity of the brain: a new view. Immunol Today. 1992;13: 507- 512.
  • Schley D, Carare-Nnadi R, Please CP, et al. Mechanis- ms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol. 2006;238:962- 974.
  • 1Beach TG, Potter PE, Kuo YM, et al. Cholinergic deafferentiation of the rabbit cortex: anew ani- mal model of A beta deposition. Neurosci Lett. 2000;283:9-12.
  • Clapham R, O’Sullivan E, Weller RO, et al. Cervical lymph nodes are found in direct relationship with the internal carotid artery: significance for the lym- phatic drainage of the brain. Clin Anat. 2010; 23:43- 47.
  • Killer HE, Laeng HR, Groscurth P. Lymphatic capil- laries in the meninges of the human optic nerve. J Neuroophhalmol. 1999;19: 222-228.
  • Killer HE, Jaggi GP, Flammer J, et al. Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional? Brain 2007;130:514-520.
  • Del Bigio MR, Enno TL. Effect of hydrocephalus on rat brain extracellular compartment. Cerebrospinal Fluid Res. 2008;5: 12.
  • Alcolado R, Weller RO, Parrish EP, et al. The cranial arachnoid and pia mater in man. Anatomical and ultrastructural observations. Neuropathol Appl Neurobiol. 1988; 14:1-17.
  • Krahn V. Leukodiapedesis and leukocyte migrati- on in the leptomeninges and in the subarachnoid space. J Neurol. 1981;226: 43-52.
  • Nicholas DS, Weller RO. The fine anatomy of the human spinal meninges A light and scanning ele- ctron microscopy study. J Neurosurg. 1988;69: 276- 282.
  • Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain-barrier disorder in Alzheimer’s di- sease. Acta Neuropathol. 2009;118:103-113.
  • Preston SD, Sterart PV, Wilkinson A, et al. Capillary and arterial cerebral amyloid angiopathy in Alzheimer’s disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathol Appl Neurobiol. 2003;29:106-117.
  • Zhang ET, Inman CB, Weller RO. Interrelations- hips of the pia mater and the perivascular (Vir- chow-Robin) spaces in the human cerebrum. J Anat. 1990;170:111-123.
  • Kida S, Steart PV, Zhang ET, et al. Perivascular cells act as scavengers in the cerebral perivas- cular spaces and remain distinct from pericytes, microglia and macrophages. Acta Neuropathol. 1993;85: 646-652.
  • Chow N, Bell RD, Deane R, et al. Serum response factor and myocardin mediate arterial hyper- contractility and cerebral blood flow dysregula- tion in Alzheimer’s phenotype. Proc Natl Acad Sci USA 2007;104: 823-828.
  • McKee AC, Gavett BE, Stern RA, et al. TDP-43 proteinopathy and motor neuron disease in ch- ronic traumatic encephalopathy. J Neuropathol Exp Neurol. 2010;69918-929.
  • Gomez-Ramos A, Diaz-Hernandez M, Cuadros R, et al. Extracellular tau is toxic to neuronal cells. FEBS Lett. 2006;580:4842-4850.
  • Gomez-Ramos A, Diaz-Hernandez M, Rubio A, et al. Extracellular tau promotes intracellular cal- cium increase through M1 and M3 muscarinic receptors in neuronal cells. Mol Cell Neuroscı. 2008;37: 673-681.
  • Price DL, Borchelt DR, Sisodia SS. Alzheimer’s disease and the prion disorders amyloid β- pro- tein and prion protein amyloidoses. Proc Natl Acad Sci USA. 1993;90: 6381-6384.
  • Schubert D, Jin L-W, Saitoh T, et al. The regulati- on of amyloid β protein precursor secretion and its modulatory role in cell adhesion. Neuron. 1989;3: 689-694.
  • Saitoh T, Sundsmo M, Roch J-M, et al. Secreted form of Amyloid β protein precursor is invol- ved in the growth regulation of fibroblasts Cell 1989;58: 615-622.
  • Klier FG, Cole G, Stalleup W, et al. Amyloid β-pro- tein precursor is associated with extracellular matrix. Brain Res 1990;515:336-342.
  • Nishimoto I, Okamoto T, Matsuura Y, et al. Alzhe- imer amyloid protein precursor complexes with brain GTP-binding protein Go. Nature 1993; 362: 75-79.
  • Shoji M, Golde T, Glisso J, et al. Production of the Alzheimer amyloid beta protein by normal proteo- lytic processing. Science 1992;258:126-129.
  • Seubert P, Vigo-Pelfrey C, Esch F, et al. Isolation and quantification of soluble Alzheimer’s beta-pepe- tide from biological fluids. Nature. 1992;359:325- 327.
  • Kanekiyo T, Ban T, Aritake K, et al. Lipocalin-type prostaglandin D synthase (β-trace) is a major amy- loid β-chaperone in human cerebrospinal fluid. PNAS. 2007;104:6412-6417.
  • Walsh DM, Selkoe DJ. Abeta oligomers- adecade of discovery. J Neurochem. 2007;101: 1172-1184.
  • Herzig MC, Winkler DT, Burgermeister P, et al. Aβ is targeted to the vasculature in a mouse model of cerebral hereditary hemorrhage with amyloidosis. Nat Neurosci. 2004;7: 954-960.
  • Revesz T, Ghiso J, Lashley T, et al. Cerebral amylo- id angiopathies: a pathologic, biochemical , and genetic view. J Neuropathol Exp Neurol. 2003;62: 885-898.
  • Rostagno A, Ghiso J. Preamyloid lesions and ce- rebrovascular deposits in the mechanism of de- mentia: Lessons from Non-β-Amyloid cerebral Amyloidosis. Neurodegenerative Diseases. 2008;5: 173-175.
  • Hardy J, Cullen K. Amyloid at the blood vessel wall. Nat Med. 2006;12: 756-757.
  • Mahley RW, Weisgraber KH, Huang Y. Apolipopro- tein E4: causative factor and therapeutic target in neuropathology including Alzheimer’s disease. PNAS 2006;103:5644-5651.
  • Buee L, Bussiere T, Buee-Scherrer V, et al. Tau pro- tein isoforms, phosphorylation and role in neuro- degenerative disorders. Brain Res rev 2000;33: 95- 130.
  • Leger JG, Brandt R, Lee G. Identification of tau pro- tein regions required for process formation in PC12 cells. J Cell Sci. 1994;107:3403-3412.
  • Alonso AD, Zaidi T, Novak M, et al. Interactions of tau isoforms with Alzheimer’s disease abnormally hyperphosphorylated tau and invitro phosphory- lation into the disease-like protein. J Biol Chem. 2001;276:37967-37973.
  • Trojanowski JQ, Lee VM. The role of tau in Alzhe- imer’s disease. Med Clin North Am. 2002; 86:615- 627.
  • Feijoo C, Campbell DG, Jakes R, et al. Evidence that phosphorylation of the microtubule-asso- ciated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly. J Cell Sci. 2005;118:397-408.
  • Drewes G. MARKing tau for tangles and toxicity. Trends Biochem Sci. 2004;29548-55. Review.
  • Avila J. Intracellular and extracellular tau. Fron- tiers in Neuroscience. 2010;4: 1-4.
  • Frost B, Diamond MI. The expanding realm of pri- on phenomena in neurodegenerative disease. Prion. 2009;3: 74-77.
  • Isaacs JD, Jackson GS, Altmann DM. The role of the cellular prion protein in the immune sys- tem. Clinical and Experimental Immunology. 2006;146:1-8.
  • Carare RO, Bernardes-Silva M, Newman TA, et al. Solutes but not cells, drain from the brain paren- chyma along basement membranes of capilla- ries and arteries. Significance of cerebral amyloid angiopathy and neuroimmunology. Neuropat- hol Appl Neurobiology. 2008; 34:131-144.
  • Sisoda SS, Price DL. Role of the β-amyloid protein in Alzheimer’s disease. FASEB J. 1995;9: 366-370.
There are 52 citations in total.

Details

Primary Language Turkish
Journal Section Collection
Authors

Hakan Erdoğan This is me

Bilal Kelten This is me

Seyho Cem Yücetaş This is me

Nilgün Çınar This is me

Alper Karaoğlan This is me

Erol Taşdemiroğlu This is me

Publication Date December 1, 2013
Published in Issue Year 2013 Volume: 5 Issue: 3

Cite

Vancouver Erdoğan H, Kelten B, Yücetaş SC, Çınar N, Karaoğlan A, Taşdemiroğlu E. Beyinin Lenfatik Drenaj ve Protein Eliminasyon Yetmezliğine Bağlı Arteriyopatileri. Maltepe tıp derg. 2013;5(3):32-40.