Causes of Arachnoid Cyst Development and Expansion
Causes of Arachnoid Cyst Development and Expansion
Arachnoid cysts are frequent incidental findings on neuroimaging studies and in clinical practice. Theories of their origin, still matter for debate, compose four categories: 1) a ball-valve mechanism; 2) an osmotic gradient between the intra- and extracystic medium; 3) primary malformation of the arachnoid membrane or cerebral lobe agenesis; and 4) fluid hypersecretion by the lining cells of the cyst wall. The cause of cyst enlargement is also debatable, although there is strong controversial evidence supporting the last two theories rather than the former. Brain water homeostasis and its regulatory pathways are weakly understood at the molecular level. In this brief report the authors attempt to add new insights into the pathogenesis of arachnoid cysts by considering aquaporin expression in the cyst wall and discuss possible future research directions and molecular targets.
Arachnoid cysts are intraarachnoid sacs containing CSF-like fluid that do not communicate with the ventricular system. They account for approximately 1% of all intracranial masses, with 50 to 60% occurring in the middle cranial fossa. Most arise as developmental anomalies. A small number are associated with neoplasms or can occur as complications following leptomeningitis, hemorrhage, or surgery. They also occur within the spinal canal, with cysts or diverticula located subdurally or in the epidural space. Spinal arachnoid cysts are commonly located dorsal to the cord in the thoracic region. Intradural spinal arachnoid cysts are caused by a congenital deficiency within the arachnoid or are the result of adhesions due to previous infection or trauma. Ultrastructural examination has shown that the cyst wall is formed from a splitting of the arachnoid membrane, with an inner and outer leaflet surrounding the cyst cavity. The origin of arachnoid cysts is still a matter of debate. Despite the numerous scientific theories, none has been proven yet. In summary, there are four proposed theories regarding the cause of these cysts: 1) a ball-valve mechanism (that is, a possible anatomical communication between the cyst and the subarachnoid space that can act as a one-way valve mechanism responsible for cyst enlargement); 2) an osmotic gradient between the intra- and extracystic medium responsible for a gradient-driven fluid transport (note that this theory lacks support given the great compositional similarity between CSF and the cyst's fluid content); 3) a malformation (that is, trapped fluid content in cerebral lobe agenesis); and 4) hypersecretive fluid production by cells lining the luminal cyst's wall.
Aquaporins act as putative water channels that have offered new insights into the water balance preservation of many anatomical regions in humans, in animals, and in plants and other microorganisms. They compose a family of 13 recognized members, numbered from 0 to 12. They are ubiquitously distributed but preferentially focused in the epithelial lining cells of tissues specialized for water secretion and absorption such as renal tubules and collecting ducts, the blood-brain barrier, and the CSF-blood barrier. In the central nervous system mainly three AQPs have been identified: AQP1 in the choroid plexus, AQP4 in the astrocytic end-feet of the blood-brain barrier, and AQP9, which was first described in tanycytes and glucose-sensitive neurons. The structural organization of AQP1 reflects a general feature of the AQP family (Fig. 1): conformational analysis of the amino acid sequence suggests a six transmembrane-spanning topography for each AQP molecule with cytosolic amino and carboxy termini with three extracellular and two intracellular loops, respectively. The amino acid sequence shows a strong similarity between the two halves of the molecule, indicating a probable evolutionary intergenic duplication. A highly conserved three amino acid motif, NPA, is present in the B and E loops of nearly all AQPs. The NPA motifs are inserted into the membrane. The intracellular B loop and the extracellular E loop fold into the membrane and interact with one another, forming a sort of hourglass characterized by wide external openings to the channel with a narrow central constriction where the NPA motifs interact and form the functional permeable pore. Taking into account the hypersecretion theory, we tested surgical specimens of normal arachnoid membrane, arachnoid cysts, and arachnoid villi for the expression of AQP1, the second member of the AQP family. We have previously studied APQ1 and found it abundantly expressed in the choroid plexus (Fig. 2), choroid plexus tumors (Fig. 3) associated with hypersecretive hydrocephalus, and cystic hemangioblastomas. The aim of this preliminary investigation was to describe the anatomical distribution of AQP1 in arachnoidal specimens in an attempt to find new data for the pathophysiological interpretation of arachnoid cyst formation and development.
(Enlarge Image)
Schema illustrating a model of AQP in the cell membrane. The subunit of the tetrameric water channel is formed from six transmembrane domains. Transmembrane hydrophobic α-helices are numbered from 1 to 6. The NPA motif is a highly conserved amino acid sequence inserted into the membrane constant for all AQPs in B and D domains. They interact, forming the functional hydrophilic pore.
(Enlarge Image)
Photomicrograph depicting normal choroid plexus with papillary projections. Immunostaining with AQP1 epitope (clone ab9566, Abcam) reveals cuboid cells expressing AQP1 at the highest degree in correspondence with the microvilli of the apical portion. Note the AQP1 expression all along the CSF-submerged surface of the choroid plexus as an uninterrupted line. Original magnification × 200.
(Enlarge Image)
Photomicrograph demonstrating hyperexpression of AQP1 in a choroid plexus papilloma with AQP1 epitope (clone ab9566, Abcam) immunostaining. Original magnification × 200.
Arachnoid cysts are frequent incidental findings on neuroimaging studies and in clinical practice. Theories of their origin, still matter for debate, compose four categories: 1) a ball-valve mechanism; 2) an osmotic gradient between the intra- and extracystic medium; 3) primary malformation of the arachnoid membrane or cerebral lobe agenesis; and 4) fluid hypersecretion by the lining cells of the cyst wall. The cause of cyst enlargement is also debatable, although there is strong controversial evidence supporting the last two theories rather than the former. Brain water homeostasis and its regulatory pathways are weakly understood at the molecular level. In this brief report the authors attempt to add new insights into the pathogenesis of arachnoid cysts by considering aquaporin expression in the cyst wall and discuss possible future research directions and molecular targets.
Arachnoid cysts are intraarachnoid sacs containing CSF-like fluid that do not communicate with the ventricular system. They account for approximately 1% of all intracranial masses, with 50 to 60% occurring in the middle cranial fossa. Most arise as developmental anomalies. A small number are associated with neoplasms or can occur as complications following leptomeningitis, hemorrhage, or surgery. They also occur within the spinal canal, with cysts or diverticula located subdurally or in the epidural space. Spinal arachnoid cysts are commonly located dorsal to the cord in the thoracic region. Intradural spinal arachnoid cysts are caused by a congenital deficiency within the arachnoid or are the result of adhesions due to previous infection or trauma. Ultrastructural examination has shown that the cyst wall is formed from a splitting of the arachnoid membrane, with an inner and outer leaflet surrounding the cyst cavity. The origin of arachnoid cysts is still a matter of debate. Despite the numerous scientific theories, none has been proven yet. In summary, there are four proposed theories regarding the cause of these cysts: 1) a ball-valve mechanism (that is, a possible anatomical communication between the cyst and the subarachnoid space that can act as a one-way valve mechanism responsible for cyst enlargement); 2) an osmotic gradient between the intra- and extracystic medium responsible for a gradient-driven fluid transport (note that this theory lacks support given the great compositional similarity between CSF and the cyst's fluid content); 3) a malformation (that is, trapped fluid content in cerebral lobe agenesis); and 4) hypersecretive fluid production by cells lining the luminal cyst's wall.
Aquaporins act as putative water channels that have offered new insights into the water balance preservation of many anatomical regions in humans, in animals, and in plants and other microorganisms. They compose a family of 13 recognized members, numbered from 0 to 12. They are ubiquitously distributed but preferentially focused in the epithelial lining cells of tissues specialized for water secretion and absorption such as renal tubules and collecting ducts, the blood-brain barrier, and the CSF-blood barrier. In the central nervous system mainly three AQPs have been identified: AQP1 in the choroid plexus, AQP4 in the astrocytic end-feet of the blood-brain barrier, and AQP9, which was first described in tanycytes and glucose-sensitive neurons. The structural organization of AQP1 reflects a general feature of the AQP family (Fig. 1): conformational analysis of the amino acid sequence suggests a six transmembrane-spanning topography for each AQP molecule with cytosolic amino and carboxy termini with three extracellular and two intracellular loops, respectively. The amino acid sequence shows a strong similarity between the two halves of the molecule, indicating a probable evolutionary intergenic duplication. A highly conserved three amino acid motif, NPA, is present in the B and E loops of nearly all AQPs. The NPA motifs are inserted into the membrane. The intracellular B loop and the extracellular E loop fold into the membrane and interact with one another, forming a sort of hourglass characterized by wide external openings to the channel with a narrow central constriction where the NPA motifs interact and form the functional permeable pore. Taking into account the hypersecretion theory, we tested surgical specimens of normal arachnoid membrane, arachnoid cysts, and arachnoid villi for the expression of AQP1, the second member of the AQP family. We have previously studied APQ1 and found it abundantly expressed in the choroid plexus (Fig. 2), choroid plexus tumors (Fig. 3) associated with hypersecretive hydrocephalus, and cystic hemangioblastomas. The aim of this preliminary investigation was to describe the anatomical distribution of AQP1 in arachnoidal specimens in an attempt to find new data for the pathophysiological interpretation of arachnoid cyst formation and development.
(Enlarge Image)
Schema illustrating a model of AQP in the cell membrane. The subunit of the tetrameric water channel is formed from six transmembrane domains. Transmembrane hydrophobic α-helices are numbered from 1 to 6. The NPA motif is a highly conserved amino acid sequence inserted into the membrane constant for all AQPs in B and D domains. They interact, forming the functional hydrophilic pore.
(Enlarge Image)
Photomicrograph depicting normal choroid plexus with papillary projections. Immunostaining with AQP1 epitope (clone ab9566, Abcam) reveals cuboid cells expressing AQP1 at the highest degree in correspondence with the microvilli of the apical portion. Note the AQP1 expression all along the CSF-submerged surface of the choroid plexus as an uninterrupted line. Original magnification × 200.
(Enlarge Image)
Photomicrograph demonstrating hyperexpression of AQP1 in a choroid plexus papilloma with AQP1 epitope (clone ab9566, Abcam) immunostaining. Original magnification × 200.
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