Search PubMedSearch

SEARCH · Search PubMed

Results for “cerebellum”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Experimental analysis of embryogenesis of cerebellum in rat. I. Subnormal growth following x-ray irradiation on day 15 of gestation.

Rat embryos of 15 days gestation were exposed in utero to 170 R of X-ray irradiation. Embryos collected 6 hours, 1, 2 and 3 days after irradiation, and animals of 2, 6, 15 and 30 days postnatal age were used for this study. Six hours after irradiation cells in the neuroepithelium and mantle layer along the roof of fourth ventricle were observed destroyed. Neuroepithelium showed only fragmentary regeneration during next two days, and it contributed to a small number of Purkinje cells. During postnatal development of cerebellum the external granular layer, the zone of proliferative cells that gives rise to neurons of postnatal origin, was found reduced. Other structures such as internal granular layer, molecular layer and medullary layer also were reduced. These multiple temporally sequenced developmental events resulted in a subnormal-sized cerebellum. Various quantitative measures helped establish that grossly the cerebellum in the X-ray irradiated animals was about half of that in the normal animals. Problems related to regeneration in the embryonic cerebellum, and to the factors determining the subnormal size of the adult cerebellum are discussed. Viewing this as an experimental approach to the study of neuroembryogenesis of cerebellum, the role of Purkinje cells in the regulation of development of cerebellum is brought out.

Animals

The resolution of dopamine and beta 1- and beta 2-adrenergic-sensitive adenylate cyclase activities in homogenates of cat cerebellum, hippocampus and cerebral cortex.

The stimulation of adenylate cyclase by dopamine and various beta-adrenergic agonists has been investigated in homogenates from 3 areas of cat brain: the cerebral cortex, cerebellum and hippocampus. The purpose of the study was to determine whether the beta-arenergic receptors coupled to adenylate cyclase could be classified as either beta 1 and beta 2 subtypes in the different regions studied. The stimulation of adenylate cyclase by the beta-adrenergic agonist, (-)isoproterenol (5 X 10(-6) M), was completely blocked by the specific beta-adrenergic antagonist, (p)alprenolol (1-(-5) M), but not by the dopaminergic antagonist, fluphenazine (10(-5) M), whereas the stimulation of adenylate cyclase by (-)epinephrine (10(-4) M) was blocked to varying extents by these two drugs in each of the 3 regions studied. The (-)epinephrine effect was always blocked in the combined presence of (p)alprenolol and fluphenazine. The adenylate cyclase stimulation by (p)epinephrine which is not blocked by (p)alprenolol was due to interaction of (p)epinephrine with a dopaminergic-sensitive adenylate cyclase which has been characterized in cerebral cortex, hippocampus and cerebellum. Regional differences in the affinity of beta-adrenergic-sensitive adenylate cyclase for various agonists were investigated in the presence of fluphenazine (10(-5) M). In the cerebellum the potency order was (+/-)protokylol greater than (+/-)hydroxybenzylisoproterenol greater than (+/-)isoproterenol greater than (-)epinephrine greater than (+/-)salbutamol greater than (-)norepinephrine, indicating the presence of a beta 2-adrenergic receptor. In the cerebral cortex the potency order was (-)isoproterenol greater than +/-)protokylol greater than (+/-)hydroxybenzylisoproterenol greater than (-)epinephrine = (-)norepinephrine ((+/-)salbutamol being inactive). A similar pattern was found in the hippocampus indicating the presence of a beta 1-adrenergic receptor in these two regions. (+/-)Salbutamol was a partial agonist in the cerebellum and a competitive antagonist in the cerebral cortex. The ratio of the antagonist potencies of (+/-)practolol and (+/-)butoxamine preferential beta 1- and beta 2-adrenergic antagonists respectively, to block the stimulation of adenylate cyclase was 25 in the cerebellum, compared to 0.5 in the cerebral cortex and 1.6 in the hippocampus. These results confirm the presence of a beta 2 subtype of receptor coupled to adenylate cyclase in the former and beta 1 subtypes in the latter two regions. The comparison between the affinities of a series of beta-adrenergic agonists and antagonists for the beta-adrenergic receptors coupled with an adenylate cyclase in cerebral cortex and cerebellum with their affinities for well characterized beta 2-adrenergic receptors in lung and beta 1-adrenergic receptor in heart substantiated this conclusion.

Adenylyl Cyclases

Alteration of the activity and molecular from of thymidine kinase during development and aging in the mouse cerebellum.

Protein, DNA and thymidine kinase levels were assayed during development and aging in the mouse cerebellum. A roughly parallel increase in protein and DNA content occurred from birth, reaching a plateau at 18 days; these adult levels increased by 30% in the 23 month-old cerebellum. Thymidine kinase activity reached a maximum at 6 postnatal days, then decreased steadily to reach, at 18 days, the low level that was maintained in the adult. The thymidine kinase synthesized in the aged cerebellum differed from that in the neonate by having (i) an increased specific activity, (ii) a faster migrating species upon electrophoresis, (iii) an inhibition by dCTP, and (iv) a lower affinity for the substrate thymidine (higher Km). Mathematical calculations indicated the appearance of a larger number of smaller sized cells in the aged cerebellum, when compared with the young adult. Histological analysis established that the newly synthesized cells were localized in the molecular layer of the old cerebellum. It appears that senescence in the mouse cerebellum may be associated with an increased synthesis of glial cells.

Aging

Studies on the mechanism of sprouting of noradrenergic terminals in rat and mouse cerebellum after neonatal 6-hydroxydopa.

The effect of various pharmacologic agents on the noradrenergic innervation of rat cerebellum was observed. It was found that the neurotoxin 6-hydroxydopa (6-OHDOPA), when given to rats at birth, caused a 46% reduction at 5 weeks of age in tyrosine hydroxylase activity in the locus coeruleus, the nucleus of origin for noradrenergic fibers innervating the cerebellum. At the same time, however, both tyrosine hydroxylase activity and NE content were elevated by 50% in the cerebellum. By treating gravid mice with the 6-OHDOPA, which crosses the placental barrier to affect the brains of developing pups, a dissociation has been shown between the elevated cerebellar NE levels and reduced telencephalic NE content. None of the other assorted pharmacological agents--namely amphetamine, metaraminol, apomorphine, alpha-methyl-p-tyrosine. L-dihydroxyphenylalanine and tyramine--when given at birth, caused a permanent elevation in cerebellar NE content. This series of studies suggests that a reduced number of noradrenergic perikarya are providing a greater innervation of the cerebellum than in control rats. Also, alteration of the telencephalic noradrenergic fibers, which are also derived from the locus coeruleus, does not appear to be a necessary event for the initiation of sprouting of noradrenergic fibers in the cerebellum. Because none of the acute-acting pharmacological agents caused a permanent elevation of NE in the cerebellum, it appears that damage, and not mere stimulation or blockade, is a necessary event for initiation of sprouting.

Animals

On the development of the cerebellum of the trout, Salmo gairdneri. I. Patterns of cell migration.

Patterns of cell migration in the cerebellum of Salmo gairneri RICHARDSON, 1836 were studied in fish ranging in length from 4.5 to 230 mm. Sagittal and transverse series were stained with haematoxylin-eosin or according to Nissl or Golgi. The cerebellum of the trout comprises three main parts, i.e. the massive corpus cerebelli, the folded valvula cerebelli and the transversely oriented lobus vestibulolateralis. The early cerebellar anlage is a simple plate, which is delimited from the tectum mesencephali by the fissura rhombo-mesencephalica. The histogenesis may be divided into three phases. During the first phase the matrix layer produces the mantle layer. During the second phase the three typical cerebellar layers are formed. The third phase is characterized by growth. As regards the first phase, the mantle layer develops throughout almost the entire extent of the cerebellar anlage. Only in a narrow paramedian strip (matrix zone M) this layer does fail to appear. In regions where the mantle layer is formed, the matrix no longer occupies the whole width of the wall and is termed the ventricular matrix. The largest part of the ventricular matrix is gradually exhausted. However, in some places this matrix persists as a layer of proliferating cells. This holds for the matrices of the caudal border of the cerebellum; matrix zone L, surrounding the lateral recesses of the fourth ventricle, and matrix zone P, connecting the matrix zones L. The mantle layer produced in the first phase of histogensis mainly develops into the ganglionic layer. The second phase of histogenesis is characterized by the formation of a secondary matrix. Newly produced cells of the matrix zones M, L and P migrate away from their sites of origin towards the regions where a mantle layer prevsiously has been formed. The majority of these cells develops into granule cells. Migration of the cells produced in the first phase of histogenesis occurs in the radial direction. Because of the curvature of the cerebellum this direction changes with respect to the main longitudinal axis of the brain from region to region. The migration paths of granule cells show variable directions, namely (a) tangential followed by radial, for granule cells in the corpus cerebelli and in the medial parts of the valvula cerebelli and the lobus vestibulolaterialis, (b) tangential, for granule cells in the lateral parts of the valvula and (c) radial, for granule cells in the lateral parts of the lobus vestibulolateralis. The analysis of these migration patterns elucidates both the histogenesis and the morphogenesis of the cerebellum of the trout.

Animals

Impairment of DNA synthesis in Gunn rat cerebellum.

Brain DNA synthesis was developmentally investigated in Gunn rat with marked cerebellar hypoplasia due to hereditary hyperbilirubinemia. In this mutant rat, the Purkinje cell was nearly selectively affected in the cerebellar cortex by bilirubin. The impaired DNA synthesis was observed in homozygous (jj) Gunn rat cerebellum, in which the DNA content and [3H]thymidine incorporation rate into DNA decreased after 10 days of age compared to those in the heterozygous (Jj)littermate. In contrast, these impairments were not found in the non-cerebellar parts of the brain and liver of jj Gunn rat. The activity of cerebellar thymidine kinase in jj Gunn rat decreased from a very early stae, being 80% of Jj rat at 6 days, and 50% at 10 days of age. The enzyme activity was not affected in the non-cerebellar parts of the brain. Although bilirubin competitively inhibited cerebellar thymidine kinase activity in vitro (15% at 10(-5) M), such bilirubin level was found to be about 1000-fold that in vivo. Moreover, photo-degradation of bilirubin in jj cerebellum exhibited no improvement in thymidine kinase activity, and the presence of an enzyme inactivator was not suggested in jj cerebellum. These results seem to indicate that the induction of thymidine kinase might be affected in jj Gunn rat cerebellum. The possibility that the impaired DNA synthesis in the external granular cells in jj cerebellum may be due to Purkinje cell damage is discussed.

Animals

A chemical study on the development of the human forebrain and cerebellum during the brain 'growth spurt' period. I. Gangliosides and plasmalogens.

Following upon previous studies on the lipid composition of the developing human brain, a further study is presented with the main object of tracing the chemical changes underlying the period of brain 'growth spurt'. Gangliosides and plasmalogens were selected as approximate markers of synaptogenesis and myelination, respectively, and these lipids were compared in cerebrum and cerebellum to establish the time, if any, at which their rate of accretion increases in a significant way. In the forebrain the rate of increase in concentration of these lipids accelerated at about the 32nd week of gestational age. Although there were too few postnatal cases to draw very firm conclusions, it seemed that the ganglioside concentration levelled off at about two months postnatal age and that the plasmalogen concentration reached a plateau between the 4th and the 6th postnatal months. In the cerebellum the concentration of gangliosides was clearly lower than that in the forebrain until about one year of age, the maximum rate of increase occurring between the last weeks of gestation and the second postnatal month. The plasmalogen concentration was somewhat higher in the cerebellum than in the forebrain but the concentration profile was similar to that followed by the gangliosides. In clear contrast with the concentration profiles in the cerebrum, in the cerebellum both lipids apparently continued to increase up to the second postnatal year. A mainly perinatal period of vulnerability is suggested for the forebrain, and a more prolonged one (probably until the second year of life) for the cerebellum.

Cerebellum

A chemical study on the development of the human forebrain and cerebellum during the brain 'growth spurt' period. II. Phosphoglyceride fatty acids.

The changes of the fatty acid composition of ethanolamine phosphoglycerides (EPG) and choline phosphoglycerides (CPG) that are associated with the maturation of the human forebrain and cerebellum have been studied. The increase in the n-3 fatty acids and the 22:4(n-6)/22:5(n-6) index in the forebrain during the second half of gestation was confirmed in the present series. In the cerebellum, on the other hand, these two parameters were higher than in the cerebrum and did not show any significant change throughout the period studied. The percentage of 18:1(n-9) changed in an opposite sense in the cerebrum and in the cerebellum, i.e. it decreased with gestational age in the cerebrum, whereas it increased markedly in the cerebellum. Consequently, the 18:0/18:1(n-9) index, which increased with maturation in the cerebrum, decreased in the cerebellum.

Cerebellum

Thyroid hormone and cell formation in the developing rat cerebellum.

Effects of neonatal hyperthyroidism on cell formation in the developing rat cerebellum were reinvestigated. Administration at birth of excessive doses of thyroxine or triiodothyronine led to an early stimulation of cell acquisition, followed by a permanent deficit of cells in the cerebellum. The corrective effects of physiological doses of thyroxine on the troubles of the histological and biochemical development of the cerebellum in thyroid-deficient animals were also studied. As early as 6 days, cell maturation and formation were already retarded in animals treated with propylthiouracil, but, as previously reported, cell formation was prolonged and the final number of cells was normal. Administration to thyroid-deficient animals of progressively increasing doses of thyroxine, nearly equal to the amounts of hormone secreted by the thyroid gland of the developing normal rat, returned the evolution of the cerebellar wet weight and of the cerebellar DNA to normal, as well as the histological maturation of the cerebellum, even if it did not entirely correct the retardation of body growth. These results are consistent with the view that thyroid hormone early stimulates maturation of the cerebellar germinative cells and subsequently interacts with cell formation in the cerebellum, and that this action is physiological.

Animals

Reciprocal transplantations between the optic tectum and the cerebellum in adult goldfish.

1. The topographic pattern of re-established visual projections after a reciprocal transplantation between tectal and cerebellar tissues was studied in adult goldfish. 2. A rectangular tissue was dissected from the left tectum, and a similar piece from the cerebellum in the same fish. The cerebellar piece was rotated by either 180 or 0 degrees around the dorsoventral axis, and transplanted into the tectum in place of the tectal piece. This tectal tissue was likewise grafted into the cerebellum after either 180 or 0 degrees rotation in the same fish. 3. The tectal graft disappeared from the cerebellum within 2 months after surgery. The operated cerebellum showed a remarkable capability for healing its excised part. No visual responses were recorded from the cerebellum. 4. The cerebellar grafts remained in place within the operated tectum in twenty fish. In fifteen of these fish, tested 3 or 4 months after surgery, the cerebellar grafts did not give any visual responses, unlike the surrounding responsive area of the tectum. These fish showed a partial scotoma in the central area of the visual field, which corresponded to the unresponsive transplanted area of the tectum. Autoradiographic examination after intraocular injection of L-[3H]proline showed that these cerebellar grafts did not contain any noticeable label, in contrast to the extensively labelled surrounding tectal tissues. 5. Sporadic visual responses were recorded from deep layers in the transplanted area of the tectum in five of the twenty fish at early post-operative periods. The receptive fields of these responses were distributed in a correct retinotopic order, regardless of whether the cerebellar tissue had been rotated by either 180 or 0 degrees. Autoradiographic examination, however, revealed that these cerebellar grafts were not invaded by regenerating optic fibres. Instead, they bypassed the interposed cerebellar tissue by making detours beneath the graft on the way towards their appropriate target zones within the tectal tissue. 6. This selective avoidance of a foreign (cerebellar) tissue and the orderly reinnervation of the proper tectal tissue by regenerating optic fibres provide us with further evidence for neuronal specificity.

Animals

Experimental analysis of embryogenesis of cerebellum in rat. II. Morphogenetic malformations following x-ray irradiation on day 18 of gestation.

Rat embryos of 18 days gestation were exposed in utero to 170 R of X-ray irradiation. Embryos were collected six hours, 1, 2, and 3 days after irradiation, and animals of 2-, 6-, 15- and 30-day-old postnatal age were sacrificed. Six hours after irradiation pyknosis of cells was notices in the external granular layer along the posterior aspect of the cerebellum. Neuroblasts, destined to differentiate into Purkinje cells, were found arrested in their migratory path. During subsequent periods of embryogenesis the external granular layer was found recovered, and clustering of the neuroblasts were disorganized and fragmented. This abnormal clustering of neuroblasts was permanent, and the external granular layer followed the same abnormal pattern in its growth. During postnatal development the internal granular layer also was found to follow the abnormal pattern of Purkinje cell layer. These abnormal developmental events were seen to lead to malformed folia in the anterior regions of the cerebellum. In addition to it the cerebellum of X-ray irradiated animals appeared smaller than the normal. Issues having a bearing on the differential radiosensitivity of different cells, factors determining the small size of the cerebellum, and cellular events determining the morphogenetic malformations are discussed.

Animals

On the development of the cerebellum of the trout, Salmo gairdneri. V. Neuroglial cells and their development.

The neuroglia of the cerebellum of Salmo gairdneri Richardson, 1836, has been studied in mature and developing specimens with light and electron microscopy. The light microscopic observations were largely carried out on Golgi material. The cerebellum of the trout contains all of the neurologlial cell types described for the mammalian cerebellum, viz. ependymal cells, Golgi epithelial cells, velate protoplasmic astrocytes, smooth protoplasmic astrocytes and oligodendrocytes. In addition two types of glial elements, which combine characteristics of ependymal cells and of velate astrocytes, are found. These elements are designated as ependymoid astrocytes and astrocytoid ependymal cells. Smooth astrocytes and oligodendrocytes were observed only in later stages of development and possibly arise from the secondary matrix. The other glial cell types, as well as transitional forms between these types, are present in rather early stages, and show a similar ultrastructure. It is plausible that all these types develop from the glioblasts produced by the ventricular matrix layer. Many glial cells are radially oriented and keep in contact with the meningeal surface throughout development. The lattice formed by matrix cells in the earliest stages, and by glial cells and the axons of granule cells later on, plays a role in directing the migration of cells. Other functions of the glia, such as dividing the cerebellar cortex in synaptic compartments, are suggested. It may be concluded that the high degree of differentiation of the teleostean cerebellum is also reflected by the morphology of the neuroglia.

Animals

Resting and reactive macrophages in the developing cerebellum: an experimental ultrastructural study.

The whole heads of 6 days old rats were exposed to 150R of X-ray irradiation to induce cell-death in the external granular layer of the cerebellum. The animals were sacrificed in a developmental sequence, and the tissue obtained from the cerebellum was prepared for electron microscopy. On the basis of the cytological criteria established for the macrophages in the cerebellum of the normal animals, characteristics of the resting and reactive macrophages and their transformation from one state to the other in the experimental animals are described. In their reactive state the macrophages showed hypertrophic and nuclear changes which were found identical to those seen in the reactive microglial elements. Issues pertaining to the ultrastructural characteristics of the macrophages, their endogenous presence in the developing cerebellum, and their transformation into the microglia cells are discussed.

Animals

The effects of postnatal hyper- and hypothyroidism on the development of D-amino acid oxidase in rat cerebellum and brain stem.

Treatment of rats with propylthiouracil for the first 30 days of postnatal life drastically retards the ontogenesis of D-amino acid oxidase in the brain stem and cerebellum. There is a marked terminal deficit of D-AAO in both the brain stem (--64%) and cerebellum (--67%) at 94 days (adults) despite the near euthyroid status at this age. If initiated early enough, thyroxine replacement therapy reverses the effects of PTU on the development of D-AAO. Hyperthyroidism significantly accelerates the development of D-AAO in both brain stem and cerebellum. Nonetheless, animals treated with thyroxine the first month of life display a net deficit of cerebellar D-AAO content in adulthood. The results are discussed in terms of the localization of D-AAO in cell types especially sensitive to thyroid hormone: (1) a cell type which is among the last to derive from the external germinal zone in the developing cerebellum, and which in the adult is located adjacent to the Purkinje cell soma; and (2) mossy fiber neurons and cerebellar glomeruli.

Animals

Morphological identification and biochemical characterization of isolated brain cell nuclei from the developing rat cerebellum.

Cell nuclei from developing rat cerebellum were isolated and the various types of nuclei were characterized and quantified. Nuclear pellets appeared to be both quantitatively and qualitatively representative of the entire cerebellum, and of sufficient purity to perform biochemical studies as well as morphological comparison with histological sections. Isolated nuclei were classified into 6 groups based on nuclear size and shape, heterochromatin aggregations, and nucleoplasmic density. The total population of cerebellar cells primarily consisted of two types of nuclei after day 10. One group of nuclei, resembling those of internal granule neurons or external germinal cells, contributed at least 70% of the total isolated cell nuclei from day 1 to day 90, whereas another nuclear group that was identified as dark oligodendrocytes constituted 8-9% of the total population on days 45 and 90. Nuclear DNA, RNA, and protein content of the cerebellum also were determined throughout postnatal development. DNA concentration markedly declined after day 15, while the RNA/DNA ratio increased until day 3 and remained constant to day 90. The nuclear protein/DNA ratio increased from birth to day 3, decreased to its lowest value on day 10, and increased to day 90. Utilizing DNA values, the total cell population as well as contributions of different cell types were calculated. At birth the cerebellum was estimated to contain 5.9 million cells, increasing to 94 million by day 21. By day 90, 107 million cells were present, of which 8.6 million oligodendrocytes and 93.6 million internal granule cells were estimated.

Aging

Role of cerebellum on ventilatory change due to muscle-receptor stimulation in the dog.

The role of the cerebellum in reflex increase of ventilation due to muscle-receptor stimulation was studied in dogs anesthetized with pentobarbital sodium. Stimulilike pressure application or stretch of gastrocnemius muscle produced increase in ventilation. Ablation or cooling of the anterior lobe of cerebellum significantly reduced this ventilatory response to application of the same degree of pressure or stretch of the gastrocnemius muscle. Ablation or cooling of the posterior lobe of the cerebellum did not have any effect on ventilation due to muscle-receptor stimulation. It was concluded that the anterior lobe of the cerebellum is in some way concerned with the ventilatory change produced by muscle-receptor activation.

Animals

Prenatal BPA exposure perturbs RNA-binding protein-mediated splicing regulation and synaptogenesis in the developing cerebellum in a sex-dependent manner.

BACKGROUND: Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social communication deficits, exhibiting a male bias in prevalence. Emerging evidence suggests that prenatal exposure to bisphenol A (BPA) may perturb neurodevelopmental trajectories relevant to ASD. While the cerebellum is increasingly recognized as a brain region implicated in ASD pathophysiology, the impact of gestational BPA exposure on its post-transcriptional alternative splicing machinery remains fundamentally undefined. METHODS: Here, we investigated sex-dependent effects of prenatal BPA exposure on the alternative splicing landscape of the neonatal rat cerebellum. We utilized RNA-seq to profile differential alternative splicing (DAS) events. Ingenuity Pathway Analysis (IPA) was used to predict biological functions and canonical pathways, and to construct the interactome network of DAS genes. To explore candidate upstream regulatory mechanisms, we performed in silico molecular docking and used high-resolution melting (HRM) qRT-PCR to validate selected splicing events. Furthermore, we assessed in vitro cellular phenotypes in primary cerebellar neurons by measuring MTS-based viability and Syn1/Psd95 puncta colocalization. RESULTS: Prenatal BPA exposure was associated with widespread DAS in genes enriched for ASD-relevant pathways in the neonatal rat cerebellum. To our knowledge, this study is the first to report molecular docking analyses predicting favorable interactions between BPA and several candidate RNA-binding proteins (RBPs), including CPEB1, RALYL, HNRNPDL, and ACO1. Our findings support a model in which BPA may perturb RBP-associated splicing regulation, including altered splicing of chromatin regulators such as Ccar1 in males. These molecular and cellular findings were accompanied by sex-stratified differences in neuronal viability and synaptic puncta measurements. BPA exposure was associated with an increased MTS viability signal in male primary cerebellar neurons, together with significant reductions in Psd95 and Syn1 puncta density, whereas female neurons showed significantly increased synaptic puncta colocalization together with reduced viability. CONCLUSIONS: In this study, we propose that prenatal BPA may be relevant to ASD-related neurodevelopmental pathways through sex-dependent changes in RBP-associated alternative splicing, including altered splicing of Ccar1 in males, together with distinct cellular outcomes. Together, these findings identify the developing cerebellum as a sensitive target of prenatal BPA exposure and highlight alternative splicing as a candidate pathway relevant to ASD biology.

Animals

The superior surface lesion of the cerebellum in children with myelomeningocele.

The lobular pattern of the superior surface of the cerebellum has been described in 100 children with myelomeningocele. There is a wide range of abnormality. The inferior displaced cerebellar segment shortens with age, but the superior surface deformity probably remains unchanged and is, therefore, useful in indicating the original extent of the caudal part of the defect in the older child. The most severe change showed the cerebellar h emispheres to be separated by a deep midline identation (split cerebellum); this was associated with hypoplasia of the superior vermis which supports an inception during the organogenetic period of development. Other cerebellums showed less severe deformities and their inception was comparatively later in development. Thus the degree of deformity of the cerebellum is probably related to its time of onset. Furthermore, the findings suggest that we are dealing with a secondary disturbance. It is evident that the cerebellar defect is not limited to its caudal aspect; this should increase the specificity of the hindbrain malformation is children with myelomeningocele.

Cerebellum