Child's Nerv Syst (1992) 8:394-398
RGNS 9 Springer-Verlag 1992
Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW[Jms Hiroshi Yamada 1, Shizuo Oi 1, Norihiko Tamaki 1, Satoshi Matsumoto 2, and Katsuko Sudo 3 1 Department of Neurosurgery, Kobe University, School of Medicine, 5-1 Kusunoki-cho, 7 Chome, Chuo-ku, Kobe, 650 Japan 2 Department of Neurosurgery, Shinsuma Hospital, Kobe, Japan 3 Institute of Medical Science, Tokyo University, Tokyo, Japan Received March 28, 1992
Abstract. Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct. Key words: Aqueductal stenosis - Congenital hydrocephalus - Subcommissural organ - Inbred rat (LEW/ Jms)
Aqueductal stenosis is one of the main causes of congenital hydrocephalus, but there is still considerable discusCorrespondence to: H. Yamada
sion about whether the aqueductal change is the cause or the result of hydrocephalus. Recently, we reported perinatal histological findings in LEW/Jms rats, a strain with congenital hydrocephalus, and concluded that aqueductal stenosis is the primary change and cause of hydrocephalus [15]. A preliminary report on this strain has appeared in another paper [13]. In this report, we describe further details of the histological features of periaqueductal structure, including the posterior commissure, subcommisural organ (SCO), and ependyma in relation to aqueductal change, and discuss the possible role of these structural changes in hydrocephalus.
Materials and methods Congenitally hydrocephalic LEW/Jms rats were used. Normal male and female siblings of the hydrocephalic rats were mated, and specimens were obtained by removing the fetuses from the pregnant females. Vaginal smears were inspected each morning for signs of sperm. The day copulation was confirmed was designated day 0 of gestation. Fetuses were collected by uterotomy on gestational days 17, 18, 19, and 20. Pups were also killed just after birth. The materials were placed in Bouin's solution and embedded in paraffin. Sagittal sections and coronal sections, 4 gm thick, of the brain were cut and stained with hematoxylin and eosin to clarify the morphological changes in the entire CSF pathway. Serial sections were prepared carefully, especially near the midline, to focus on the aqueductal changes. The morphological changes in the aqueduct and midbrain of the hydrocephalic rats were then compared with those of normal siblings.
Results The aqueduct in coronal sections from normal newborn rats was shown to be patent throughout its entire length, with the narrowest site triangular in section and the base facing the dorsal side, as reported before [15]. The usual ependyma was absent in the center of the base facing the dorsal side, having been replaced by tall columnar cells (Fig. 1). The central part of the aqueduct r o o f was composed of these structures, which was a continuation of the
395
Fig. 1. Coronal sections of aqueduct in a normal and b hydrocephalic rat. In normal rat, the usual ependymawas absent in the center of the base facingthe dorsal side, havingbeen replaced by tall columnar cells. By contrast, in hydrocephalicrats the ependyma encircled the aqueductal cavity. The number of ependymal cells forming the aqueduct in hydrocephalicrats was less than that observed in normal rats
caudal site of the SCO. This structure continued from the junction between the III ventricle and aqueduct to the neighborhood of the IV ventricle. On the other hand, in hydrocephalic rats, this characteristic structure disappeared near the part with the smallest diameter. However, closer to the IV ventricle, this structure appeared similar to that in normal rats. In hydrocephalic rats, the ependyma encircled the aqueductal cavity in an oval shape. The number of ependymal cells forming the aqueduct in hydrocephalic rats was less than that observed in normal rats (Fig. 1). On gestational day 20, both normal and hydrocephalic rats showed development of the SCO, but the SCO in hydrocephalic rats was shorter than in normal rats in midline sagittal sections. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimensioin was large in comparison with normal rats. The superior collicular commissure, located at the caudal side of posterior commissure, ran along the ventral side of the midbrain in hydrocephalus. There was an area of cell paucity just dorsal to the superior collicular commissure. On gestational day 19, midline sagittal sections showed almost the same findings as in newborn rats. Although the SCO was well visualized in both rats, it was shorter in hydrocephalus. The superior collicular commissure ran ventrally, and thickening of the rostral midbrain was evident in hydrocephalic rats. These findings were also noted in rats at days 17 and 18 of gestation. On gestational day 17, there was no difference in ventricular size between rats with a patent and those with an obstructed aqueduct. The SCO and posterior commissure were poorly developed in the hydrocephalic rats, but well developed in rats with a
patent aqueduct. Throughout all gestational periods, a poorly developed SCO and thickening of the rostral midbrain were notable histological fndings (Figs. 2, 3).
Discussion
In coronal sections of the midbrain, the aqueduct was shown to be patent for its entire length, with the narrowest site triangular in section and a base facing the dorsal side. This shape was thought to be determined by the structures surrounding the aqueduct, including the aqueductal gray matter, red nucleus on the ventral side, posterior commissure and SCO on the dorsal side. The SCO is a specialized part of the ependyma, which appears as columnar epithelial cells. It is located in the caudal part of the III ventricle and the cephalic part of the aqueduct. However, these columnar cells vary in size relative to the caudal location, i.e., the height of the cells decreases. The histological characteristics of the SCO have been well studied, especially with reference to a possible glandular secretory function [3, 10-12, 14]. Schmidt and D'Agostino [14] suggested basal secretion by the columnar epithelial cells and an endocrine function for the SCO. Brown and Afifi [3] investigated the possible role of the SCO in water metabolism and control of thirst. In man, the SCO is conspicuous during the early stages of embryonic development. According to Rakic and Sidman [1l], the SCO appears on embryonic day 11-15 in mice, and persist throughout life thereafter. However in humans, the SCO regresses after birth, and in adults only remnants of its parenchyma can be detected. In this study, histological observation was started from embryonic day 17, when normal rats showed a welldeveloped SCO and posterior commissure. However, in hydrocephalic rats, these structures were not well developed. In addition, bending and thickening of the dorsal midbrain were observed. In coronal sections of the aqueduct in newborn rats, the aqueduct was not completely surrounded by the same ependyma, as is the case in normal rats. The number of ependymal cells forming the aqueduct in hydrocephalic rats was less than that observed in normal rats. This strongly indicates that aque-
396
397
Fig. 3a-f. Magnified midsagittal sections of the rostral side of the aqueduct in normal (a, e, e) and hydrocephalic (b, d, f) rats on gestational days 19 (a, b), 18 (e, d), and 17 (e, 0. The subcommissural organ (arrow) and posterior commissure (asterisk) are well developed in normal rat, whereas they are poorly developed in hydrocephalic rat, especially on gestational day 17 Fig. 2a-h. Midsagittal sections of the aqueduct in normal (a, c, e, g) and hydrocephalic (b, d, f, h) rats on gestational days 20 (a, b), 19 (c, d), 18 (e, f), and 17 (g, h) At all gestational times, the aqueduct is patent in normal rats and obstructed in hydrocephalic rats. There is a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension is large in comparison with normal rats
ductal occlusion is due to a developmental anomaly. In addition, the central p a r t o f the a q u e d u c t r o o f was composed o f unusual structures, which was a c o n t i n u a t i o n o f the caudal site o f the SCO. This structure continued f r o m the j u n c t i o n between the I I I ventricle and a q u e d u c t to the n e i g h b o r h o o d o f the IV ventricle in n o r m a l rats, whereas in hydrocephalic rats this characteristic structure disappeared near the part with the smallest diameter. H o w e v er, closer to the IV ventricle, this structure appeared similar to that in n o r m a l rats. Congenital h y d r o c e p h a l i c models have been reported in m a n y strains, but only a small n u m b e r o f strains show p r i m a r y closure o f the a q u e d u c t [1, 4, 7, 8, ~5]. The p a t h o -
398 logical manifestations described here are very similar to those reported recently for another strain of rat, H-Tx, with a recessive mutation for hydrocephalus, although there remains some controversy as to the cause o f hydrocephalus in H-Tx [9]. Jones demonstrated the light micrographs of H-Tx, showing thickening of the overlying midbrain and shortening of the SCO [7]. Their findings were thus similar to ours. In man, aqueductal stenosis is reported to be one of the causes of hydrocephalus [2, 5, 6], but the histological features o f the periaqueductal change have not been well discussed. The present study shows the hypodevelopment of SCO and posterior commissure from gestational day 17, and hydrocephalus has not been reported at this stage before [15]. This indicates that poor development of SCO was not a secondary change caused by hydrocephalus. Although the role of the SCO has been much discussed from the viewpoint of secretory function, further study must be done from the viewpoint of a regulation of development in the neighborhood of the aqueduct.
11. Rakic P, Sidman RL (1968) Subcommissural organ and adjacent ependyma: autoradiographic study of their origin in the mouse brain. Am J Anat 122:317-336 12. Rodriguez EM, Oksche A, Hein S, Rodriguez S, Yulis R (1984) Spatial and structural interrelationships between secretory cells of the subcommissural organ and blood vessels. An immunocytochemical study. Cell Tissue Res 237:443-449 13. Sasaki S, Goto H, Nagano H, Furuya K, Omata Y, Kanazawa K, Suzuki K, Sudo K (1983) Congenital hydrocephalus revealed in the inbred rat LEW/Jms. Neurosurgery 13:548-554 14. Schmidt WR, D'Agostino AN (1966) The subcommissural organ of the adult rabbit: an electron microscopic study. Neurology 16:373-379 15. Yamada H, Shizuo Oi, Tamaki N, Matsumoto S, Sudo K (1991) Prenatal aqueductal stenosis as a cause of congenital hydrocephalus in the inbred rat LEW/Jms. Child's Nerv Syst 7: 218222
References
Editorial comment
1. Aikawa H, Kobayashi S, Suzuki K (1986) Aqueductal lesions in 6-aminonicotinamide-treated suckling mouse. Acta Neuropathol 71:243-250 2. Bicker DS, Adams RD (1949) Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus. Brain 72:246- 262 3. Brown D, Afifi AK (1967) Histological and ablation studies on the relation of the subcommissural organ and rostral midbrain to sodium water metabolism. Anat Rec 153:255-264 4. D'Amato CJ, O'Shea KS, Hicks SP, Glover RA, Annesley TM (1986) Genetic prenatal aqueductal stenosis with hydrocephalus in rat. J Neuropathol Exp Neurol 45:665-682 5. Edward JH, Norman RM, Roberts JM (1961) Sex-linked hydrocephalus. Report of a family with 15 affected members. Arch Dis Child 36:481-485 6. Holmes LB, Nash A, ZuRhein GM, Levin M, Opitz M (1963) X-linked aqueductal stenosis: clinical and neuropathological findings in two families. Pediatrics 63:1104-1110 7. Jones HC, Bucknall RM (1988) Inherited prenatal hydrocephalus in the H-Tx rat: a morphological study. Neuropathol Appl Neurobiol 14:263-274 8. Jones HC, Dack S, Ellis C (1987) Morphological aspects of the development of hydrocephalus in a mouse mutant (SUMS/NP), Acta Neuropathol 72:268-276 9. Kohn DF, Chinookoswong N, Chou SM (1981) A new model of congenital hydrocephalus in the rat. Acta Neuropathol 54:211-218 10. Oksche A (1969) The subcommissural organ. J Neurovisceral Rel Suppl IX:111-139
Most forms of congenital hydrocephalus are of the noncommunicating type and associated with obstruction of aqueduct of Sylvius. They are referred to as aqueductal stenosis associated either with gliosis or forking of the aqueduct. The etiologies are not known, with the exception of some cases where maternal infections, teratogenic events, or inheritance can be recognized. There is an Xlinked form of congenital hydrocephalus. The experiments carried out by the authors on congenitally hydrocephalic rats are o f paramount importance, because they contribute to clarifying the problem whether aqueductal stenosis is the cause or the consequence of hydrocephalus. The occlusion of the aqueduct in hydrocephalic rats has been found as due to a developmental anomaly, in which the subcommissural organ and posterior commissure participate. Ependyma also shows anomaly. The article is a stimulus to further investigate the aqueductal region in congenital hydrocephalus in man, taking into account that, as far as we know today, forking of the aqueduct is usually associated with other congenital anomalies, whereas gliosis is due to a hyperplasia of subependymal glia which most probably depends on previous inflammatory events. D. Schiffer, Turin
RGNS 9 Springer-Verlag 1992
Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW[Jms Hiroshi Yamada 1, Shizuo Oi 1, Norihiko Tamaki 1, Satoshi Matsumoto 2, and Katsuko Sudo 3 1 Department of Neurosurgery, Kobe University, School of Medicine, 5-1 Kusunoki-cho, 7 Chome, Chuo-ku, Kobe, 650 Japan 2 Department of Neurosurgery, Shinsuma Hospital, Kobe, Japan 3 Institute of Medical Science, Tokyo University, Tokyo, Japan Received March 28, 1992
Abstract. Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct. Key words: Aqueductal stenosis - Congenital hydrocephalus - Subcommissural organ - Inbred rat (LEW/ Jms)
Aqueductal stenosis is one of the main causes of congenital hydrocephalus, but there is still considerable discusCorrespondence to: H. Yamada
sion about whether the aqueductal change is the cause or the result of hydrocephalus. Recently, we reported perinatal histological findings in LEW/Jms rats, a strain with congenital hydrocephalus, and concluded that aqueductal stenosis is the primary change and cause of hydrocephalus [15]. A preliminary report on this strain has appeared in another paper [13]. In this report, we describe further details of the histological features of periaqueductal structure, including the posterior commissure, subcommisural organ (SCO), and ependyma in relation to aqueductal change, and discuss the possible role of these structural changes in hydrocephalus.
Materials and methods Congenitally hydrocephalic LEW/Jms rats were used. Normal male and female siblings of the hydrocephalic rats were mated, and specimens were obtained by removing the fetuses from the pregnant females. Vaginal smears were inspected each morning for signs of sperm. The day copulation was confirmed was designated day 0 of gestation. Fetuses were collected by uterotomy on gestational days 17, 18, 19, and 20. Pups were also killed just after birth. The materials were placed in Bouin's solution and embedded in paraffin. Sagittal sections and coronal sections, 4 gm thick, of the brain were cut and stained with hematoxylin and eosin to clarify the morphological changes in the entire CSF pathway. Serial sections were prepared carefully, especially near the midline, to focus on the aqueductal changes. The morphological changes in the aqueduct and midbrain of the hydrocephalic rats were then compared with those of normal siblings.
Results The aqueduct in coronal sections from normal newborn rats was shown to be patent throughout its entire length, with the narrowest site triangular in section and the base facing the dorsal side, as reported before [15]. The usual ependyma was absent in the center of the base facing the dorsal side, having been replaced by tall columnar cells (Fig. 1). The central part of the aqueduct r o o f was composed of these structures, which was a continuation of the
395
Fig. 1. Coronal sections of aqueduct in a normal and b hydrocephalic rat. In normal rat, the usual ependymawas absent in the center of the base facingthe dorsal side, havingbeen replaced by tall columnar cells. By contrast, in hydrocephalicrats the ependyma encircled the aqueductal cavity. The number of ependymal cells forming the aqueduct in hydrocephalicrats was less than that observed in normal rats
caudal site of the SCO. This structure continued from the junction between the III ventricle and aqueduct to the neighborhood of the IV ventricle. On the other hand, in hydrocephalic rats, this characteristic structure disappeared near the part with the smallest diameter. However, closer to the IV ventricle, this structure appeared similar to that in normal rats. In hydrocephalic rats, the ependyma encircled the aqueductal cavity in an oval shape. The number of ependymal cells forming the aqueduct in hydrocephalic rats was less than that observed in normal rats (Fig. 1). On gestational day 20, both normal and hydrocephalic rats showed development of the SCO, but the SCO in hydrocephalic rats was shorter than in normal rats in midline sagittal sections. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimensioin was large in comparison with normal rats. The superior collicular commissure, located at the caudal side of posterior commissure, ran along the ventral side of the midbrain in hydrocephalus. There was an area of cell paucity just dorsal to the superior collicular commissure. On gestational day 19, midline sagittal sections showed almost the same findings as in newborn rats. Although the SCO was well visualized in both rats, it was shorter in hydrocephalus. The superior collicular commissure ran ventrally, and thickening of the rostral midbrain was evident in hydrocephalic rats. These findings were also noted in rats at days 17 and 18 of gestation. On gestational day 17, there was no difference in ventricular size between rats with a patent and those with an obstructed aqueduct. The SCO and posterior commissure were poorly developed in the hydrocephalic rats, but well developed in rats with a
patent aqueduct. Throughout all gestational periods, a poorly developed SCO and thickening of the rostral midbrain were notable histological fndings (Figs. 2, 3).
Discussion
In coronal sections of the midbrain, the aqueduct was shown to be patent for its entire length, with the narrowest site triangular in section and a base facing the dorsal side. This shape was thought to be determined by the structures surrounding the aqueduct, including the aqueductal gray matter, red nucleus on the ventral side, posterior commissure and SCO on the dorsal side. The SCO is a specialized part of the ependyma, which appears as columnar epithelial cells. It is located in the caudal part of the III ventricle and the cephalic part of the aqueduct. However, these columnar cells vary in size relative to the caudal location, i.e., the height of the cells decreases. The histological characteristics of the SCO have been well studied, especially with reference to a possible glandular secretory function [3, 10-12, 14]. Schmidt and D'Agostino [14] suggested basal secretion by the columnar epithelial cells and an endocrine function for the SCO. Brown and Afifi [3] investigated the possible role of the SCO in water metabolism and control of thirst. In man, the SCO is conspicuous during the early stages of embryonic development. According to Rakic and Sidman [1l], the SCO appears on embryonic day 11-15 in mice, and persist throughout life thereafter. However in humans, the SCO regresses after birth, and in adults only remnants of its parenchyma can be detected. In this study, histological observation was started from embryonic day 17, when normal rats showed a welldeveloped SCO and posterior commissure. However, in hydrocephalic rats, these structures were not well developed. In addition, bending and thickening of the dorsal midbrain were observed. In coronal sections of the aqueduct in newborn rats, the aqueduct was not completely surrounded by the same ependyma, as is the case in normal rats. The number of ependymal cells forming the aqueduct in hydrocephalic rats was less than that observed in normal rats. This strongly indicates that aque-
396
397
Fig. 3a-f. Magnified midsagittal sections of the rostral side of the aqueduct in normal (a, e, e) and hydrocephalic (b, d, f) rats on gestational days 19 (a, b), 18 (e, d), and 17 (e, 0. The subcommissural organ (arrow) and posterior commissure (asterisk) are well developed in normal rat, whereas they are poorly developed in hydrocephalic rat, especially on gestational day 17 Fig. 2a-h. Midsagittal sections of the aqueduct in normal (a, c, e, g) and hydrocephalic (b, d, f, h) rats on gestational days 20 (a, b), 19 (c, d), 18 (e, f), and 17 (g, h) At all gestational times, the aqueduct is patent in normal rats and obstructed in hydrocephalic rats. There is a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension is large in comparison with normal rats
ductal occlusion is due to a developmental anomaly. In addition, the central p a r t o f the a q u e d u c t r o o f was composed o f unusual structures, which was a c o n t i n u a t i o n o f the caudal site o f the SCO. This structure continued f r o m the j u n c t i o n between the I I I ventricle and a q u e d u c t to the n e i g h b o r h o o d o f the IV ventricle in n o r m a l rats, whereas in hydrocephalic rats this characteristic structure disappeared near the part with the smallest diameter. H o w e v er, closer to the IV ventricle, this structure appeared similar to that in n o r m a l rats. Congenital h y d r o c e p h a l i c models have been reported in m a n y strains, but only a small n u m b e r o f strains show p r i m a r y closure o f the a q u e d u c t [1, 4, 7, 8, ~5]. The p a t h o -
398 logical manifestations described here are very similar to those reported recently for another strain of rat, H-Tx, with a recessive mutation for hydrocephalus, although there remains some controversy as to the cause o f hydrocephalus in H-Tx [9]. Jones demonstrated the light micrographs of H-Tx, showing thickening of the overlying midbrain and shortening of the SCO [7]. Their findings were thus similar to ours. In man, aqueductal stenosis is reported to be one of the causes of hydrocephalus [2, 5, 6], but the histological features o f the periaqueductal change have not been well discussed. The present study shows the hypodevelopment of SCO and posterior commissure from gestational day 17, and hydrocephalus has not been reported at this stage before [15]. This indicates that poor development of SCO was not a secondary change caused by hydrocephalus. Although the role of the SCO has been much discussed from the viewpoint of secretory function, further study must be done from the viewpoint of a regulation of development in the neighborhood of the aqueduct.
11. Rakic P, Sidman RL (1968) Subcommissural organ and adjacent ependyma: autoradiographic study of their origin in the mouse brain. Am J Anat 122:317-336 12. Rodriguez EM, Oksche A, Hein S, Rodriguez S, Yulis R (1984) Spatial and structural interrelationships between secretory cells of the subcommissural organ and blood vessels. An immunocytochemical study. Cell Tissue Res 237:443-449 13. Sasaki S, Goto H, Nagano H, Furuya K, Omata Y, Kanazawa K, Suzuki K, Sudo K (1983) Congenital hydrocephalus revealed in the inbred rat LEW/Jms. Neurosurgery 13:548-554 14. Schmidt WR, D'Agostino AN (1966) The subcommissural organ of the adult rabbit: an electron microscopic study. Neurology 16:373-379 15. Yamada H, Shizuo Oi, Tamaki N, Matsumoto S, Sudo K (1991) Prenatal aqueductal stenosis as a cause of congenital hydrocephalus in the inbred rat LEW/Jms. Child's Nerv Syst 7: 218222
References
Editorial comment
1. Aikawa H, Kobayashi S, Suzuki K (1986) Aqueductal lesions in 6-aminonicotinamide-treated suckling mouse. Acta Neuropathol 71:243-250 2. Bicker DS, Adams RD (1949) Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus. Brain 72:246- 262 3. Brown D, Afifi AK (1967) Histological and ablation studies on the relation of the subcommissural organ and rostral midbrain to sodium water metabolism. Anat Rec 153:255-264 4. D'Amato CJ, O'Shea KS, Hicks SP, Glover RA, Annesley TM (1986) Genetic prenatal aqueductal stenosis with hydrocephalus in rat. J Neuropathol Exp Neurol 45:665-682 5. Edward JH, Norman RM, Roberts JM (1961) Sex-linked hydrocephalus. Report of a family with 15 affected members. Arch Dis Child 36:481-485 6. Holmes LB, Nash A, ZuRhein GM, Levin M, Opitz M (1963) X-linked aqueductal stenosis: clinical and neuropathological findings in two families. Pediatrics 63:1104-1110 7. Jones HC, Bucknall RM (1988) Inherited prenatal hydrocephalus in the H-Tx rat: a morphological study. Neuropathol Appl Neurobiol 14:263-274 8. Jones HC, Dack S, Ellis C (1987) Morphological aspects of the development of hydrocephalus in a mouse mutant (SUMS/NP), Acta Neuropathol 72:268-276 9. Kohn DF, Chinookoswong N, Chou SM (1981) A new model of congenital hydrocephalus in the rat. Acta Neuropathol 54:211-218 10. Oksche A (1969) The subcommissural organ. J Neurovisceral Rel Suppl IX:111-139
Most forms of congenital hydrocephalus are of the noncommunicating type and associated with obstruction of aqueduct of Sylvius. They are referred to as aqueductal stenosis associated either with gliosis or forking of the aqueduct. The etiologies are not known, with the exception of some cases where maternal infections, teratogenic events, or inheritance can be recognized. There is an Xlinked form of congenital hydrocephalus. The experiments carried out by the authors on congenitally hydrocephalic rats are o f paramount importance, because they contribute to clarifying the problem whether aqueductal stenosis is the cause or the consequence of hydrocephalus. The occlusion of the aqueduct in hydrocephalic rats has been found as due to a developmental anomaly, in which the subcommissural organ and posterior commissure participate. Ependyma also shows anomaly. The article is a stimulus to further investigate the aqueductal region in congenital hydrocephalus in man, taking into account that, as far as we know today, forking of the aqueduct is usually associated with other congenital anomalies, whereas gliosis is due to a hyperplasia of subependymal glia which most probably depends on previous inflammatory events. D. Schiffer, Turin
