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The Histologic Structure of the Human Pineal Body
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The Histologic Structure of the Human Pineal Body K. S C H A R E N B E R G
AND
L. LISS
University of Michigan, Ann Arbor, Mich. (U.S.A.)
The pineal body has been known to man since the time of Galen and has been studied by numerous investigators. Still there is much that is hypothetical or obscure concerning our knowledge of this organ, although considerable information has been collected. The parenchymal elements of the pineal body were difficult to stain until Del Rio Hortega introduced the silver carbonate method which has proved superior to the older techniques. However, even Hortega himself was compelled to resort to drawings in order to demonstrate details of the parenchymal elements. In this presentation we have dispensed with drawings and illustrated the histology of the pineal body by unretouched photomicrographs. Parenchyma
The parenchyma of the pineal body is comprised of lobules with a definite cytoarchitectural pattern and surrounded by connective tissue septa (Fig. 1). The lobules contain 3 varieties of elements: (1) The elements of the perivascular or marginal plexuses; (2) The polymorph cells of the central area of the lobules; (3) The pinealocytes of the peripheral layers of the pineal body adjacent to its astroglia capsule. The marginal plexuses form a ring of elements with numerous processes, while the inner strata are less rich in cells (Fig. 2). The marginal plexuses contain several types of elements: (1) Cells with oval bodies and very long processes which increase in caliber towards the periphery of the lobule and terminate as an intertwined network (Fig. 3). (2) Elements with long processes which terminate as loops or bundles of delicate fibers and merge with the perivascular structures (Fig. 4). (3) Large, pear-shaped cells, each with a single long process which terminates as massive club-like ending (Fig. 3). (4) Cells with large oval cell bodies and several short, widely branched, interconnected processes with very numerous club-like endings (Fig. 5). ( 5 ) Elements of irregular shape with several strong processes, but with few clubs (Fig. 6).
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In the marginal plexuses, the relationship between the parenchyma and the endothelium of the vessels is close. In cross sections, the parenchymal elements form a dense sleeve around the vessels (Fig. 7); in longitudinal and tangential sections the endbulbs of the parenchymal elements appear to be in immediate proximity to the endothelial layer, but were not observed to penetrate this layer (Fig. 8).
Fig. 1. Glandular structure of the pineal body: the lobules are surrounded by connective tissue septa which carry vessels and nerves, x 30.
The cellular composition of the perivascular plexuses is not uniform. In some, the elements with short processes and numerous club-like endings predominate (Fig. 8) ; other plexuses contain numerous cells with very long processes which penetrate the plexuses and are lost in the perivascular structures, as has been mentioned previously
(Fig. 4).
In the centralparts of the lobules, the elements are distinctly different from those of the plexuses. The cells have an oval body and a maze of intertwined processes; there is no definite cytoarchitectural pattern (Fig. 9). In the marginal parenchyma the predominate element is a unipolar cell with a round cell body and one wide, frequently arched process filled with coarse granules (Fig. 10). Some of these cells have very long processes which end on the capillaries (Fig. 11). In addition, there are small elements with numerous processes. The consensus is that the parenchymal cells contain numerous granular bodies which surround the nuclei, fill the cytoplasm and extend into the processes. Del Rio Hortega analysed these bodies in man and mammals (ox, sheep) by use of the silver
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Fig. 2. Parenchyma of a lobule at higher magnification: the marginal plexus is built of cells with a round or elongated body and numerous processes ending with clubs. Deeper strata contain irregular cells, x 200.
carbonate technique and found very numerous granules throughout the cellular framework. He is in agreement with the majority of authors that these granules represent secretory products. We also found numerous granules in the parenchyma elements of an 8-year-old child (Fig. 12). In middle aged men, the granules are frequently of large size in areas of advanced degeneration of the parenchyma. These granules stain an intense black with silver carbonate and stand out distinctly. In astroglial scars the remnants of parenchymal cells are transformed into large spherical bodies which gradually break into amorphous fragments (Fig. 13). The nature of these inclusions is still problematical. It is likely that in functioning elements they represent secretory products, but it cannot be doubted that morphologically identical bodies are present in advanced state of degeneration when secretory activity cannot be assumed. Hortega stated that the pineal cells belong to a special type, neither nervous nor neuroglial, but they possess characters common with the two cell types mentioned. In our opinion, there are fundamental differences between the neurons of the peripheral and the central nervous systems and the parenchyma cells of the pineal body; the latter terminate near or on the endothelia of the vessels and in the adventitial network,
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The manner of contact between the parenchymal process and the endothelium suggests an endapparatus. In the brain and in the peripheral nervous system there is no such direct contact between the nerve cells and vessels; in both situations the relations are effected by the perisomatic and the periaxonic glia (Del Rio Hortega and others, Scharenberg). This fundamental difference places the parenchymal cells of the pineal body in a special category.
Fig. 3. Marginal plexus of a lobule contains elements with one process and very massive single club; other cells carry numerous clubs, x 200.
According to Hortega, the structural pattern of the parenchyma is that of a gland : he stated that the ‘Knowledge gathered thus far enables . . . to affirm that the cells . . . are elements differentiated for the discharge of a non-nervous function . , . probably a secretory function’. Experimental observations by Lerner and Case (melatonin) and Farrell (glomerulotropic hormones) support the conclusions of Hortega. Astroglia The pineal body contains very numerous astrocytes. These elements were investigated by Del Rio Hortega with the gold chloride method of Cajal; however, the silver carbonate variant for impregnation of these cells (Del Rio Hortega-Scharenberg) permits a more detailed analysis of their distribution and activity. The astrocytes are more numerous in man than in other mammals (horse, cattle).
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The pineal body is surrounded by a capsule of large astrocytes which form a peripheral network and are connected with the astroglia of the lobules (Fig. 14). The architecture of the latter is very distinct: in the center of the lobule there are one or more giant astrocytes (monster glia of Weigert). Such an astrocyte has an oval cell body and numerous radiating processes which fill the interparenchymal spaces (Fig. 15).
Fig. 4. Septum contains numerous wide vessels, the adventitia of which contains numerous intertwined cells; pinealocytes with very long processes with brush-like endings merge with the structure of the adventitia, x 200.
Degeneration and proliferation of the astroglia are very common. Degenerated astrocytes are frequently hypertrophic. In such an astrocyte the intracellular structures are bulky and the perikaryon is filled with coarse intertwined fibers; the processes are wide and the entire cell is strongly argentophile (Fig. 16). Degeneration of the parenchyma of an entire lobule stimulates formation of a ring of large cells around the destroyed area (Fig. 17). Destruction of several adjacent lobules results in the formation of massive glial scars which frequently attain macroscopic proportions (Fig. 18), and can be recognized as white islets in unstained tissue. These scars are very dense and stain intensely with silver carbonate. Del Rio Hortega stated that the pineal body contains a very small number of interstitial neuroglial elements as compared with the elements of parenchyma. This opinion can no longer be maintained as has been demonstrated here. The discrepancy is explained by the greater efficiency of the new modifications of the silver carbonate.
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Fig. 5. Detailed part of a marginal pinealocyte with numerous processes ending with clubs, x 200.
Fig. 6. Pinealocyte of the marginal plexus with a large body and two massive processes, one of which branches out but carries very few clubs, x 200.
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Fig. 7. Perivascular plexus which surrounds a capillary with a dense ring of cells. There are irregularly shaped elements of the deeper strata of the lobule, x 100.
Fig. 8. Perivascular plexus with numerous elements, the processes of which enter the adventitia, x 200.
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Fig. 9. Irregularly shaped pinealocytes with long processes present in deeper strata of the lobules x 200.
Fig. 10. Pinealocytes of the capsule of the pineal body with one strong process and oval body, x 200.
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Fig. 11 .Two pinealocytes from thecapsule of the pineal body with processes ending on a vessel, x 300.
Fig. 12. Parenchymal element with numerous secretion granules, x 300.
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Fig. 13. Degenerated parenchymal cells filled with countless granular bodies, x 200.
Fig. 14. Superficial capsule of the pineal body built of coarse intertwined processes of astrocytes, x 200.
THE HISTOLOGIC STRUCTURE OF THE HUMAN PINEAL BODY
Fig. 15. Two astrocytes in the center of a lobule, x 200.
Fig. 16. Degenerated astrocytes in the center of a lobule, x 200.
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Fig. 17. Ring of pIoliferated astroglia which surrounds a degenerated lobule, x 200.
Fig. 18. Massive astroglia scar in the central part of a lobule, x 30.
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These modifications disclose an intense activity of the astroglia in all age groups. Already in the first decade of life extensive scars may be present, in the 2nd and 3rd decades they are common and can frequently be seen with the unaided eye. Astroglial activity is stimulated by the degeneration of the parenchyma which invariably occurs ; proliferation of the astroglia is less common in advanced age. Ner yes
Thick bundles of mostly unmyelinated nerves enter the tissue of the septa and follow the course of the capillaries. Their fibers surround the vessels, dichotomize, send numerous branches into the parenchyma and dissociate among its elements (Figs. 19, 20). Some of the nerves cross the septa and enter the adjacent lobules (Fig. 21).
Fig. 19. Perivascular nervous plexus in a septum, x 200.
Numerous dense nerve bundles also enter the epiphysis from the habenular and posterior commissures and can be seen near the capsule (Fig. 22); they divide into small plexuses and finally into single fibers (Fig. 23). There are numerous endformations of the nerves which can frequently be traced to parenchymal elements: (1) Endformations with definite relation to parenchyma: (a) Single fibers with an elongated club-like ending (Fig. 24); (b) Single fibers with a large oval endbulb (Fig. 25); (c) End buttons on a single parenchymal cell formed by two fibers (Fig. 26); (d) Endformations which contact two or more parenchymal elements and are formed by three or four fibers (Fig. 27). ( 2 ) Finally there are large buttons which terminate without distinct relation to parenchymal cells (Fig. 28).
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Fig. 20. Nervous plexus in a septum with branches entering a lobule,
X
200.
Fig. 21. Nerve plexus which pass through the septum and enter the opposite lobule, x 200.
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Fig. 22. Nerve bundles from the habenular and posterior commissures as will be seen near the capsule, x 200.
Fig. 23. Nerve bundles which run between the parenchyma of a lobule, x 200.
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Fig. 24. A nerve fiber which ends on a parenchymal cell with a club-like thickening, x 200.
Fig. 25. Endformations of two nerve fibers on the parenchymal cells, x 200.
(3) Dense whorls of fibers in the perilobular structures which send strong branches into the parenchyma and are lost among its elements (Fig. 29). The presence of an extensive system of nerves in the pineal body was already known to older investigators (Kolliker, 1850; Meynert, Cionini). Later on, Krabbe, Achucarro and Sacristan, Cutore, Marburg and others contributed much to this problem. As a result of these investigations there is consensus that there is (a) a central and
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Fig. 26. Nerves ending on the body of parenchymal cells, x 200.
Fig. 27. Three nerve fibers which connect two parenchymal elements, x 200.
(b) a sympathetic innervation of the pineal body. Endformations of the nerves to the pineal body were traced to parenchymal elements by Walter, who believed that these fibers come from the commissures. We confirmed the findings of Walter, but were not able to decide whether the endformations are those of the surface bundles or those of the perivascular plexuses; nor is
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Fig. 28. Two nerve fibersendingwithclubs without visibleconnection with parenchymal elements, x 200.
Fig. 29. Nerve plexus of the whorl type in the septa of a lobule, x 200.
it possible to distinguish histologically sympathetic from sensory fibers. However, it is reasonable to assume that the nerves with endformations on parenchymal elements are sympathetic in origin. Solution of this problem can only be expected from experimental investigation.
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There still are many gaps in the knowledge of the nervous supply of the pineal body. In spite of a close contact between nerves and vessels, no perivascular plexuses have ever been described. It seems that the nerves use the perivascular structures as avenues of approach (Kappers). As previously stated, there are also whorls of nerves with strong processes which break up within the parenchyma (Fig. 29). These formations have no connections with the vessels although they are present in the structures of the septa. Their nature is obscure. The nerves of the pineal body, regardless of their physiological functions or histologic structure are interconnected by numerous collaterals and must be regarded as constituting a closely linked system. The nerves of the parenchyma, especially those with endformations on the pinealocytes, frequently show definite degenerative phenomena. Numerous beady swellings appear near the end of the fiber and break down into fragments (Fig. 30), or the nerve
Fig. 30. Fragmented and degenerated nerve in the center of the picture; on the left and right there are two nerve endings, x 200.
is transformed into a hypertrophic beady chain (Fig. 31) which can be traced to degenerated parenchymal elements. These changes are illustrated in the pineal body of a healthy child who died an accidental death. They suggest a possible relation between the degeneration of the nerves and of the parenchyma. Connective tissue
Under low power the connective tissue of the septa consists of a network of coarse and fine fibers. The coarse variety has wide meshes but few nuclei (Fig. 32). At higher magnification, the delicate fibers are seen to form a dense capsule in which the individual fibers can hardly be distinguished. In the maze of these delicate fibers are
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embedded numerous, large, oval nuclei (Fig. 33). These delicate structures are situated just above the astroglial capsule of the lobules. The vessels of the septa are wide capillaries with thin walls; they form sinuses and
Fig. 31. Degenerated and fragmented nerve in a degenerated lobule, x 200.
Fig. 32. Coarse connective tissue network in a septum, x 200.
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are surrounded by connective tissue fibers (Fig. 34). The latter form coarse structures which fill out the septa, enter the parenchyma of the lobules and spread among the parenchymal elements to end with loops, rings, endswellings and basket-like structures
Fig. 33. Delicate network of fibers and cells in a septum, x 200.
Fig. 34. Connective tissue impregnation of the adventitia of vessels in a septum,
X
200.
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(Fig. 36). These endformations are present in the immediate vicinity of the pinealocytes and some of them end on the parenchymal elements. These intralobular fibers are present at all ages, but their number declines in ad-
Fig. 35. Part of a coarse connectivetissue network which enters a degenerated lobule, x 200.
Fig. 36. Endformations of connective tissue in the parenchyma of a lobule, x 300.
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Fig. 37. Proliferated connective tissue which replaces degenerated structures of several lobules, x 200.
Fig. 38. A large acervulus of almost amorphous structure surrounded by a ring of connective tissue and remnants of degenerated cells, x 200.
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vanced age. Degenerative phenomena of the connective tissue in the pineal body are common and are simultaneous with degeneration of the parenchyma. The intralobular fibers proliferate, appear hypertrophic, lose their endformations and form a coarse network; in these areas only a few degenerated pinealocytes remain. In the final stage of degeneration, massive connective tissue scars replace the parenchyma (Fig. 37). Corpora acervuli A well-known degenerative change in the pineal body is the occurrence of numerous ‘sand particles’, or areas of hyaline degeneration or calcification in the parenchyma. These bodies may occur in early childhood, become more numerous between the 7th and the 14th year, and are almost constant after the 16th year. Occasionally they are absent in the adult (Krabbe). They vary in size and may reach macroscopic proportions and become visible in rontgenograms. The presence of these acervuli or corpora arenacea has been known since the discovery of the pineal body and has been investigated by numerous authors over a period of 300 years. They have been regarded as normal by some investigators (Merckel) and as pathological by others (Heller, Santorini). The averculi also occur in animals (sheep, donkey and horse). The morphology of the acervuli varies somewhat; they are mostly globular, less often oval in shape, and are frequently almost amorphous (Fig. 38), but often contain concentric rings, which suggest a vascular origin (Fig. 39). These ring-like structures are surrounded by parenchymal elements, proliferated astroglia and connective tissue fibers. Numerous concrements may occur in the glia of the habenular commissure and in the pia (Bargmann). Amprino described coraliform acervuli or concrements, an observation confirmed by Bargmann. Their presence of acervuli at any age and the absence of clinical symptoms associated with their formation deny their pathological significance.
Fig. 39. Acervulus with a distinct larger structure, x 200.
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SUMMARY
The parenchyma of the pineal body is comprised of lobules with a definite cytoarchitectural pattern and surrounded by connective tissue septa. The lobules contain three varieties of elements. At low power, the marginal plexuses form a ring of elements with numerous processes, while the inner strata are less rich in cells, and contain several types of elements. The pineal body is surrounded by a capsule of large astrocytes which form a peripheral network and are interconnected with the astroglia of the lobules. In the center of the lobule there are one or more giant astrocytes (monster glia of Weigert), which have an oval cell body and numerous radiating processes which fill the interparenchymal spaces. Degeneration and proliferation of the astroglia are very common. In degenerated astrocytes which are frequently hypertrophic, the intracellular structures are bulky and the perikaryon is filled with coarse intertwined fibers; the processes are wide and the entire cell is strongly argentophile. Oligodendroglia have not been previously described in the pineal body. We have been able to impregnate elements with large round bodies and long dichotomized processes identical with oligodendroglia of type I1 of Hortega. The relationship of these cells to other elements could not be ascertained. Microglia may occur in degenerated areas (Hortega). Thick bundles of mostly unmyelinated nerves enter the tissue of the septa and follow the course of the capillaries. Their fibers surround the vessels, dichotomize, send numerous branches into the parenchyma and dissociate among its elements. Some of the nerves cross the septa and enter the adjacent lobules. Numerous dense nerve bundles also enter the epiphysis from the habenular and posterior commissures and can be seen near the capsule; they divide into small plexuses and finally into single fibers. There are numerous endformations of the nerves which can frequently be traced to parenchymal elements. Under low power the connective tissue of the septa consists of a network of coarse and fine fibers. The coarse variety has wide meshes but few nuclei. At higher magnification, the delicate fibers are seen to form a dense capsule in which the individual fibers can hardly be distinguished. In the maze of these delicate fibers are embedded numerous, large, oval nuclei. These delicate structures are situated just above the astroglial capsule of the lobules. DISCUSSION
WOLFE:Dr. Scharenberg have you seen in the rat pineal organ club endings of pineal cells which I gather are extraordinary hard to recognize? SCHARENBERG: I worked only with the human pineal.
The Histologic Structure of the Human Pineal Body K. S C H A R E N B E R G
AND
L. LISS
University of Michigan, Ann Arbor, Mich. (U.S.A.)
The pineal body has been known to man since the time of Galen and has been studied by numerous investigators. Still there is much that is hypothetical or obscure concerning our knowledge of this organ, although considerable information has been collected. The parenchymal elements of the pineal body were difficult to stain until Del Rio Hortega introduced the silver carbonate method which has proved superior to the older techniques. However, even Hortega himself was compelled to resort to drawings in order to demonstrate details of the parenchymal elements. In this presentation we have dispensed with drawings and illustrated the histology of the pineal body by unretouched photomicrographs. Parenchyma
The parenchyma of the pineal body is comprised of lobules with a definite cytoarchitectural pattern and surrounded by connective tissue septa (Fig. 1). The lobules contain 3 varieties of elements: (1) The elements of the perivascular or marginal plexuses; (2) The polymorph cells of the central area of the lobules; (3) The pinealocytes of the peripheral layers of the pineal body adjacent to its astroglia capsule. The marginal plexuses form a ring of elements with numerous processes, while the inner strata are less rich in cells (Fig. 2). The marginal plexuses contain several types of elements: (1) Cells with oval bodies and very long processes which increase in caliber towards the periphery of the lobule and terminate as an intertwined network (Fig. 3). (2) Elements with long processes which terminate as loops or bundles of delicate fibers and merge with the perivascular structures (Fig. 4). (3) Large, pear-shaped cells, each with a single long process which terminates as massive club-like ending (Fig. 3). (4) Cells with large oval cell bodies and several short, widely branched, interconnected processes with very numerous club-like endings (Fig. 5). ( 5 ) Elements of irregular shape with several strong processes, but with few clubs (Fig. 6).
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In the marginal plexuses, the relationship between the parenchyma and the endothelium of the vessels is close. In cross sections, the parenchymal elements form a dense sleeve around the vessels (Fig. 7); in longitudinal and tangential sections the endbulbs of the parenchymal elements appear to be in immediate proximity to the endothelial layer, but were not observed to penetrate this layer (Fig. 8).
Fig. 1. Glandular structure of the pineal body: the lobules are surrounded by connective tissue septa which carry vessels and nerves, x 30.
The cellular composition of the perivascular plexuses is not uniform. In some, the elements with short processes and numerous club-like endings predominate (Fig. 8) ; other plexuses contain numerous cells with very long processes which penetrate the plexuses and are lost in the perivascular structures, as has been mentioned previously
(Fig. 4).
In the centralparts of the lobules, the elements are distinctly different from those of the plexuses. The cells have an oval body and a maze of intertwined processes; there is no definite cytoarchitectural pattern (Fig. 9). In the marginal parenchyma the predominate element is a unipolar cell with a round cell body and one wide, frequently arched process filled with coarse granules (Fig. 10). Some of these cells have very long processes which end on the capillaries (Fig. 11). In addition, there are small elements with numerous processes. The consensus is that the parenchymal cells contain numerous granular bodies which surround the nuclei, fill the cytoplasm and extend into the processes. Del Rio Hortega analysed these bodies in man and mammals (ox, sheep) by use of the silver
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Fig. 2. Parenchyma of a lobule at higher magnification: the marginal plexus is built of cells with a round or elongated body and numerous processes ending with clubs. Deeper strata contain irregular cells, x 200.
carbonate technique and found very numerous granules throughout the cellular framework. He is in agreement with the majority of authors that these granules represent secretory products. We also found numerous granules in the parenchyma elements of an 8-year-old child (Fig. 12). In middle aged men, the granules are frequently of large size in areas of advanced degeneration of the parenchyma. These granules stain an intense black with silver carbonate and stand out distinctly. In astroglial scars the remnants of parenchymal cells are transformed into large spherical bodies which gradually break into amorphous fragments (Fig. 13). The nature of these inclusions is still problematical. It is likely that in functioning elements they represent secretory products, but it cannot be doubted that morphologically identical bodies are present in advanced state of degeneration when secretory activity cannot be assumed. Hortega stated that the pineal cells belong to a special type, neither nervous nor neuroglial, but they possess characters common with the two cell types mentioned. In our opinion, there are fundamental differences between the neurons of the peripheral and the central nervous systems and the parenchyma cells of the pineal body; the latter terminate near or on the endothelia of the vessels and in the adventitial network,
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The manner of contact between the parenchymal process and the endothelium suggests an endapparatus. In the brain and in the peripheral nervous system there is no such direct contact between the nerve cells and vessels; in both situations the relations are effected by the perisomatic and the periaxonic glia (Del Rio Hortega and others, Scharenberg). This fundamental difference places the parenchymal cells of the pineal body in a special category.
Fig. 3. Marginal plexus of a lobule contains elements with one process and very massive single club; other cells carry numerous clubs, x 200.
According to Hortega, the structural pattern of the parenchyma is that of a gland : he stated that the ‘Knowledge gathered thus far enables . . . to affirm that the cells . . . are elements differentiated for the discharge of a non-nervous function . , . probably a secretory function’. Experimental observations by Lerner and Case (melatonin) and Farrell (glomerulotropic hormones) support the conclusions of Hortega. Astroglia The pineal body contains very numerous astrocytes. These elements were investigated by Del Rio Hortega with the gold chloride method of Cajal; however, the silver carbonate variant for impregnation of these cells (Del Rio Hortega-Scharenberg) permits a more detailed analysis of their distribution and activity. The astrocytes are more numerous in man than in other mammals (horse, cattle).
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The pineal body is surrounded by a capsule of large astrocytes which form a peripheral network and are connected with the astroglia of the lobules (Fig. 14). The architecture of the latter is very distinct: in the center of the lobule there are one or more giant astrocytes (monster glia of Weigert). Such an astrocyte has an oval cell body and numerous radiating processes which fill the interparenchymal spaces (Fig. 15).
Fig. 4. Septum contains numerous wide vessels, the adventitia of which contains numerous intertwined cells; pinealocytes with very long processes with brush-like endings merge with the structure of the adventitia, x 200.
Degeneration and proliferation of the astroglia are very common. Degenerated astrocytes are frequently hypertrophic. In such an astrocyte the intracellular structures are bulky and the perikaryon is filled with coarse intertwined fibers; the processes are wide and the entire cell is strongly argentophile (Fig. 16). Degeneration of the parenchyma of an entire lobule stimulates formation of a ring of large cells around the destroyed area (Fig. 17). Destruction of several adjacent lobules results in the formation of massive glial scars which frequently attain macroscopic proportions (Fig. 18), and can be recognized as white islets in unstained tissue. These scars are very dense and stain intensely with silver carbonate. Del Rio Hortega stated that the pineal body contains a very small number of interstitial neuroglial elements as compared with the elements of parenchyma. This opinion can no longer be maintained as has been demonstrated here. The discrepancy is explained by the greater efficiency of the new modifications of the silver carbonate.
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Fig. 5. Detailed part of a marginal pinealocyte with numerous processes ending with clubs, x 200.
Fig. 6. Pinealocyte of the marginal plexus with a large body and two massive processes, one of which branches out but carries very few clubs, x 200.
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Fig. 7. Perivascular plexus which surrounds a capillary with a dense ring of cells. There are irregularly shaped elements of the deeper strata of the lobule, x 100.
Fig. 8. Perivascular plexus with numerous elements, the processes of which enter the adventitia, x 200.
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Fig. 9. Irregularly shaped pinealocytes with long processes present in deeper strata of the lobules x 200.
Fig. 10. Pinealocytes of the capsule of the pineal body with one strong process and oval body, x 200.
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Fig. 11 .Two pinealocytes from thecapsule of the pineal body with processes ending on a vessel, x 300.
Fig. 12. Parenchymal element with numerous secretion granules, x 300.
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Fig. 13. Degenerated parenchymal cells filled with countless granular bodies, x 200.
Fig. 14. Superficial capsule of the pineal body built of coarse intertwined processes of astrocytes, x 200.
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Fig. 15. Two astrocytes in the center of a lobule, x 200.
Fig. 16. Degenerated astrocytes in the center of a lobule, x 200.
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Fig. 17. Ring of pIoliferated astroglia which surrounds a degenerated lobule, x 200.
Fig. 18. Massive astroglia scar in the central part of a lobule, x 30.
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These modifications disclose an intense activity of the astroglia in all age groups. Already in the first decade of life extensive scars may be present, in the 2nd and 3rd decades they are common and can frequently be seen with the unaided eye. Astroglial activity is stimulated by the degeneration of the parenchyma which invariably occurs ; proliferation of the astroglia is less common in advanced age. Ner yes
Thick bundles of mostly unmyelinated nerves enter the tissue of the septa and follow the course of the capillaries. Their fibers surround the vessels, dichotomize, send numerous branches into the parenchyma and dissociate among its elements (Figs. 19, 20). Some of the nerves cross the septa and enter the adjacent lobules (Fig. 21).
Fig. 19. Perivascular nervous plexus in a septum, x 200.
Numerous dense nerve bundles also enter the epiphysis from the habenular and posterior commissures and can be seen near the capsule (Fig. 22); they divide into small plexuses and finally into single fibers (Fig. 23). There are numerous endformations of the nerves which can frequently be traced to parenchymal elements: (1) Endformations with definite relation to parenchyma: (a) Single fibers with an elongated club-like ending (Fig. 24); (b) Single fibers with a large oval endbulb (Fig. 25); (c) End buttons on a single parenchymal cell formed by two fibers (Fig. 26); (d) Endformations which contact two or more parenchymal elements and are formed by three or four fibers (Fig. 27). ( 2 ) Finally there are large buttons which terminate without distinct relation to parenchymal cells (Fig. 28).
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Fig. 20. Nervous plexus in a septum with branches entering a lobule,
X
200.
Fig. 21. Nerve plexus which pass through the septum and enter the opposite lobule, x 200.
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Fig. 22. Nerve bundles from the habenular and posterior commissures as will be seen near the capsule, x 200.
Fig. 23. Nerve bundles which run between the parenchyma of a lobule, x 200.
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Fig. 24. A nerve fiber which ends on a parenchymal cell with a club-like thickening, x 200.
Fig. 25. Endformations of two nerve fibers on the parenchymal cells, x 200.
(3) Dense whorls of fibers in the perilobular structures which send strong branches into the parenchyma and are lost among its elements (Fig. 29). The presence of an extensive system of nerves in the pineal body was already known to older investigators (Kolliker, 1850; Meynert, Cionini). Later on, Krabbe, Achucarro and Sacristan, Cutore, Marburg and others contributed much to this problem. As a result of these investigations there is consensus that there is (a) a central and
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Fig. 26. Nerves ending on the body of parenchymal cells, x 200.
Fig. 27. Three nerve fibers which connect two parenchymal elements, x 200.
(b) a sympathetic innervation of the pineal body. Endformations of the nerves to the pineal body were traced to parenchymal elements by Walter, who believed that these fibers come from the commissures. We confirmed the findings of Walter, but were not able to decide whether the endformations are those of the surface bundles or those of the perivascular plexuses; nor is
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Fig. 28. Two nerve fibersendingwithclubs without visibleconnection with parenchymal elements, x 200.
Fig. 29. Nerve plexus of the whorl type in the septa of a lobule, x 200.
it possible to distinguish histologically sympathetic from sensory fibers. However, it is reasonable to assume that the nerves with endformations on parenchymal elements are sympathetic in origin. Solution of this problem can only be expected from experimental investigation.
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There still are many gaps in the knowledge of the nervous supply of the pineal body. In spite of a close contact between nerves and vessels, no perivascular plexuses have ever been described. It seems that the nerves use the perivascular structures as avenues of approach (Kappers). As previously stated, there are also whorls of nerves with strong processes which break up within the parenchyma (Fig. 29). These formations have no connections with the vessels although they are present in the structures of the septa. Their nature is obscure. The nerves of the pineal body, regardless of their physiological functions or histologic structure are interconnected by numerous collaterals and must be regarded as constituting a closely linked system. The nerves of the parenchyma, especially those with endformations on the pinealocytes, frequently show definite degenerative phenomena. Numerous beady swellings appear near the end of the fiber and break down into fragments (Fig. 30), or the nerve
Fig. 30. Fragmented and degenerated nerve in the center of the picture; on the left and right there are two nerve endings, x 200.
is transformed into a hypertrophic beady chain (Fig. 31) which can be traced to degenerated parenchymal elements. These changes are illustrated in the pineal body of a healthy child who died an accidental death. They suggest a possible relation between the degeneration of the nerves and of the parenchyma. Connective tissue
Under low power the connective tissue of the septa consists of a network of coarse and fine fibers. The coarse variety has wide meshes but few nuclei (Fig. 32). At higher magnification, the delicate fibers are seen to form a dense capsule in which the individual fibers can hardly be distinguished. In the maze of these delicate fibers are
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embedded numerous, large, oval nuclei (Fig. 33). These delicate structures are situated just above the astroglial capsule of the lobules. The vessels of the septa are wide capillaries with thin walls; they form sinuses and
Fig. 31. Degenerated and fragmented nerve in a degenerated lobule, x 200.
Fig. 32. Coarse connective tissue network in a septum, x 200.
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are surrounded by connective tissue fibers (Fig. 34). The latter form coarse structures which fill out the septa, enter the parenchyma of the lobules and spread among the parenchymal elements to end with loops, rings, endswellings and basket-like structures
Fig. 33. Delicate network of fibers and cells in a septum, x 200.
Fig. 34. Connective tissue impregnation of the adventitia of vessels in a septum,
X
200.
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(Fig. 36). These endformations are present in the immediate vicinity of the pinealocytes and some of them end on the parenchymal elements. These intralobular fibers are present at all ages, but their number declines in ad-
Fig. 35. Part of a coarse connectivetissue network which enters a degenerated lobule, x 200.
Fig. 36. Endformations of connective tissue in the parenchyma of a lobule, x 300.
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Fig. 37. Proliferated connective tissue which replaces degenerated structures of several lobules, x 200.
Fig. 38. A large acervulus of almost amorphous structure surrounded by a ring of connective tissue and remnants of degenerated cells, x 200.
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vanced age. Degenerative phenomena of the connective tissue in the pineal body are common and are simultaneous with degeneration of the parenchyma. The intralobular fibers proliferate, appear hypertrophic, lose their endformations and form a coarse network; in these areas only a few degenerated pinealocytes remain. In the final stage of degeneration, massive connective tissue scars replace the parenchyma (Fig. 37). Corpora acervuli A well-known degenerative change in the pineal body is the occurrence of numerous ‘sand particles’, or areas of hyaline degeneration or calcification in the parenchyma. These bodies may occur in early childhood, become more numerous between the 7th and the 14th year, and are almost constant after the 16th year. Occasionally they are absent in the adult (Krabbe). They vary in size and may reach macroscopic proportions and become visible in rontgenograms. The presence of these acervuli or corpora arenacea has been known since the discovery of the pineal body and has been investigated by numerous authors over a period of 300 years. They have been regarded as normal by some investigators (Merckel) and as pathological by others (Heller, Santorini). The averculi also occur in animals (sheep, donkey and horse). The morphology of the acervuli varies somewhat; they are mostly globular, less often oval in shape, and are frequently almost amorphous (Fig. 38), but often contain concentric rings, which suggest a vascular origin (Fig. 39). These ring-like structures are surrounded by parenchymal elements, proliferated astroglia and connective tissue fibers. Numerous concrements may occur in the glia of the habenular commissure and in the pia (Bargmann). Amprino described coraliform acervuli or concrements, an observation confirmed by Bargmann. Their presence of acervuli at any age and the absence of clinical symptoms associated with their formation deny their pathological significance.
Fig. 39. Acervulus with a distinct larger structure, x 200.
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SUMMARY
The parenchyma of the pineal body is comprised of lobules with a definite cytoarchitectural pattern and surrounded by connective tissue septa. The lobules contain three varieties of elements. At low power, the marginal plexuses form a ring of elements with numerous processes, while the inner strata are less rich in cells, and contain several types of elements. The pineal body is surrounded by a capsule of large astrocytes which form a peripheral network and are interconnected with the astroglia of the lobules. In the center of the lobule there are one or more giant astrocytes (monster glia of Weigert), which have an oval cell body and numerous radiating processes which fill the interparenchymal spaces. Degeneration and proliferation of the astroglia are very common. In degenerated astrocytes which are frequently hypertrophic, the intracellular structures are bulky and the perikaryon is filled with coarse intertwined fibers; the processes are wide and the entire cell is strongly argentophile. Oligodendroglia have not been previously described in the pineal body. We have been able to impregnate elements with large round bodies and long dichotomized processes identical with oligodendroglia of type I1 of Hortega. The relationship of these cells to other elements could not be ascertained. Microglia may occur in degenerated areas (Hortega). Thick bundles of mostly unmyelinated nerves enter the tissue of the septa and follow the course of the capillaries. Their fibers surround the vessels, dichotomize, send numerous branches into the parenchyma and dissociate among its elements. Some of the nerves cross the septa and enter the adjacent lobules. Numerous dense nerve bundles also enter the epiphysis from the habenular and posterior commissures and can be seen near the capsule; they divide into small plexuses and finally into single fibers. There are numerous endformations of the nerves which can frequently be traced to parenchymal elements. Under low power the connective tissue of the septa consists of a network of coarse and fine fibers. The coarse variety has wide meshes but few nuclei. At higher magnification, the delicate fibers are seen to form a dense capsule in which the individual fibers can hardly be distinguished. In the maze of these delicate fibers are embedded numerous, large, oval nuclei. These delicate structures are situated just above the astroglial capsule of the lobules. DISCUSSION
WOLFE:Dr. Scharenberg have you seen in the rat pineal organ club endings of pineal cells which I gather are extraordinary hard to recognize? SCHARENBERG: I worked only with the human pineal.