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Giriş ve Amaç: Cerebellum merkezi sinir sisteminde gelişimine embriyonik (E) olarak en erken dönemde başlayıp, postnatal (P) dönemde en geç olarak tamamlayan yapılardan biridir. Bu tez çalışmasında, farklı çevresel koşullarda yetiştirilen sıçanların motor davranışlarında ve cerebellum‟larında meydana gelen morfolojik değişikliklerin karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: Spraque-Dawley cinsi sıçanlar (her iki cins ve grup için sekiz adet olmak üzere), E14-P44 günleri arasında standart, zenginleştirilmiş veya öngörülemeyen tekrarlı stres ortamı koşullarında yetiştirilmiştir. Deney hayvanlarının motor becerileri ve koordinasyon düzeylerinde meydana gelen değişiklikler erken (P27-P29) ve geç (P42-P44) evrede uygulanan modifiye grip ve rota-rod testleri ile değerlendirilmiştir. Daha sonra uygun anestezi koşulları altında kardiyak perfüzyonla sakrifiye edilen hayvanların sağ serebellar hemisfer ve vermis bölgelerinden alınan histolojik kesitlerde stereolojik yöntemlerle sayımlar yapılmıştır. Sol serebellar hemisferler ise Golgi-Cox metodu ile boyanarak, Purkinje hücrelerindeki dendritik dikensi çıkıntı yoğunlukları ve tipleri analiz edilmiştir. Bulgular: Zenginleştirilmiş koşullarda yetiştirilen yavruların modifiye grip testindeki skorları diğer gruplara göre daha yüksek bulunmuştur. Bu gruptaki hayvanların adrenal bez ağırlığının vücut ağırlığına oranlarında ise anlamlı bir düşüş gözlenmiştir. Morfometrik analizlerde granüler tabakanın (GT) moleküler tabaka (MT) hacmine oranı vermis bölgesinden alınan histolojik kesitlerde benzerlik gösterirken, serebellar hemisferden alınan kesitlerde, zenginleştirilmiş veya stres ortamında yetiştirilen erkeklerde kontrol gruplarınınkine kıyasla daha yüksek bulunmuştur. Öte yandan birim mesafeye düşen Purkinje hücre sayısı kontrol gruplarındaki erkeklerde daha yüksek bulunmuştur. Derin serebellar çekirdeklerden nucleus fastigii‟de optik parçalama yöntemiyle hesaplanan toplam nöron sayısında gruplar arasında fark görülmemesine rağmen, cinsiyetler arasındaki karşılaştırmalarda dişilerin lehine bir artış olduğu gözlenmiştir. Nucleus dentatus‟ta ise zenginleştirilmiş ortamda yetiştirilen erkeklerdeki toplam nöron sayısı kontrol ve stres gruplarına göre anlamlı artış göstermiştir. Purkinje nöronlarındaki dikensi çıkıntıların yoğunlukları her iki cinsiyette de zenginleştirilmiş ortamda yetiştirilen hayvanlarda daha yüksek bulunmuştur. Ġki yönlü varyans analizi sonuçları dikensi çıkıntı yoğunluğu ile yetiştirme koşulları arasında anlamlı bir etkileşim olduğunu göstermiştir. Sonuç ve Öneriler: Purkinje hücrelerinin aksine postnatal dönemde de gelişimlerine devam eden granüler hücreler periferden ve kortikal merkezlerden gelen liflerle çok sayıda sinaptik bağlantılar kurmaktadır. Bu süreçte maruz kalınan farklı çevresel koşullar kortikal tabaka hacimlerinde, bu tabakalarda yerleşim gösteren nöronların sayısal yoğunluklarında ve dendritik dikensi çıkıntı morfolojileri üzerinde değişikliklere yol açmak suretiyle sinaptik plastisite düzeylerinde, cinsiyet faktörüne de bağımlı olarak, önemli farklılıklara neden olmaktadır. Serebellar kortikal hacim oranlarında meydana gelen değişiklikler filogenetik açıdan değerlendirildiğinde, gelişimini daha erken evrelerde tamamlayan bölgelerin çevresel koşul değişikliklerinden daha az etkilendiği gözlenmektedir. Tam tersine serebellar hemisferlerde ve bu bölgelerle bağlantılı olan derin serebellar çekirdeklerde gözlenen farklılıklar cerebellum‟un, motor koordinasyondaki rolüne ilaveten, emosyonel ve bilişsel işlevlerin bütünleştirilmesinde ve düzenlenmesinde de önemli görevler üstlendiğine işaret etmektedir. Introduction and Aim: Cerebellum is one of the structures of the central nervous system in which development starts as early as embryonic (E) and completes as late as postnatal (P) periods. In this thesis study, we aimed to compare motor behaviors and morphological changes of the cerebellum in rats raised in different environmental conditions. Materials and Methods: Spraque-Dawley rats (eight for both sexes and groups) were grown in standard, enriched or unpredictable repetitive stress conditions between E14-P44 days. Changes in motor skills and coordination levels of experimental animals were evaluated with modified grip and rota-rod tests applied at early (P27-P29) and late (P42-P44) stages. The histological sections obtained from the right cerebellar hemisphere and vermis regions of the animals, sacrificed by cardiac perfusion under appropriate anesthesia conditions, were then counted by stereological methods. Left cerebellar hemispheres were stained with Golgi-Cox method to analyze dendritic spine densities and types in the Purkinje cells. Results: In the modified grip test, scores of animals raised in enriched conditions were higher than those of other groups. A significant decrease was observed in the adrenal to body weight ratio of animals in this group. Morphometric analyzes showed similar ratios in the volumes of granular (GL) to molecular layer (ML) in the histological sections taken from the vermis. Whereas in sections taken from the cerebellar hemisphere, this ratio was higher in males raised in enriched or stressed conditions than those raised in control conditions. On the other hand, the number of Purkinje cells per unit distance was higher in the males of control group. Although there was no significant difference in the total number of neurons in the fastigial nucleus, calculated by the optical fractionator method, among the groups; gender comparisons displayed an increase in favor of the females. In the dentate nucleus, the total number of neurons in males grown in enriched conditions increased significantly compared to the control and stress groups. In both genders, the densities of dendritic spines in the Purkinje cells were higher in animals grown in enriched conditions. Two-way analysis of variance results showed a significant interaction between dendritic spine density and environmental conditions. Conclusion and Suggestions: In contrast to the Purkinje cells, granular cells continue to develop in the postnatal period and form numerous synaptic connections with fibers coming from the periphery and cortical centers. Different environmental conditions exposed during this period cause significant differences in the synaptic plasticity levels by causing alterations in the volumes of cortical layers, the numerical densities of the neurons located in these layers, and the dendritic spine morphologies, in a gender-dependent way. When the changes in the cerebellar cortical volume ratios are evaluated from a phylogenetic point of view, it is observed that the regions completing their development at the earlier stages are less affected by the environmental condition changes. On the contrary, differences observed in the cerebellar hemispheres and the deep cerebellar nuclei associated with these regions indicate that the cerebellum, in addition to its role in motor coordination, plays important roles in the integration and regulation of emotional and cognitive functions.

SUMMARY In contrast to the pathology of the so-called temporal or psychomotor epilepsy which has been thoroughly investigated in recent times, there has been, until now, no corresponding research into the so-called petit mal or centrencephalic epilepsy. We are therefore making a detailed examination of the clinico-anatomical connections between a case of idiopathic epilepsy with impulsive petit mal (also called myoclonic petit mal with multi-spikes-waves) and grand mal on awakening. The case in question concerns a 28-year old woman who ever since the age of 16 had suffered from convulsions of varying severity, occurring either singly or several at a time, in her shoulders, neck and arms, without however losing consciousness, frequently following lack of sleep and consumption of alcohol, and mainly after waking in the morning. During the whole course of the disease only 7 grand mal occurred which appeared mainly after waking and were characterized by opisthotonus during the seizure and extreme cyanosis. The cause of death was probably suicide. With reference to our pathological examination the following remarks can be made: 1. No evidence was discovered which could be diagnosed as responsible for causing the disease. 2. In view of the clinically benign course of the disease, the extent of the ictal damage was surprisingly great. We interpreted this as a consequence of the especially serious impulsive grand mal which took the form of paroxysmal herniations. 3. The sequence of ictal damage usually expected in idiopathic epilepsies according to Scholz varied somewhat in our case, in that the Ammon's horn was affected least of all. On the other hand, the most serious changes took place in the cerebellar cortex, the nucleus dentatus and, strangely enough, in the nucleus ruber. The predilection towards ictal damage in mesencephalic and cerebellar structures is completely consistent with the functional structures of the rubro-neuronal system, which for clinical reasons have been diagnosed already as responsible for this type of petit mal. 4. The discovery of inhibited migration in the cerebellar cortex seemed significant to us in explaining the age dependency of impulsive petit mal, as well as a series of anomalies of constitution and growth characteristic of this manifestation of the disease. The question is raised as to how far disturbances of the development of this kind, which are too minor to be decisive for the aetiology, are an aid to lending profile to the characteristic features of the special clinical picture. RESUME Au contraire de ce qui a ete fait pour la pathologie de l'epilepsie dite temporale ou psycho-motrice, qui a ete etudiee a fond ces derniers temps, on n'a pas effectue jusqu'a present de recherches analogues concernant ce qu'on appelle le petit mal ou epilepsie centrencephalique. Pour cette raison, nous faisons un examen detaille des rapports clinico-anatomiques entre un cas d'epilepsie idiopathique avec petit mal impulsif (aussi appele petit mal myoclonique avec polypointes-ondes) et le grand mal au reveil. Le cas en question concerne une femme de 28 ans qui, depuis l'age de 16 ans a souffert de convulsions de gravite variable, se manifestant seules ou plusieures a la fois, dans les epaules, le cou et les bras, sans pourtant qu'elle perde connaissance, et generalement a la suite d'un manque de sommeil et de consommation d'alcool, et presque toujours le matin, apres le reveil. Durant tout le cours de la maladie, il n'y a eu que 7 crises de grand mal, generalement au reveil, avec opisthotonos au cours de la crise et une cyanose extrěme. La cause de la mort est probablement le suicide. Nous referant a notre etude pathologique, nous pouvons faire les remarques suivantes: 1. On n'a pu decouvrir aucune preuve qui puisse ětre consideree comme responsable d'avoir provoque la maladie. 2. Si l'on considere le cours, cliniquement benin, de la maladie, la lesion causee par les crises est extrěmement etendue. Nous avons interprete ceci comme la consequence des crises de grand mal impulsif particulierement graves, qui ont pris l'aspect de formations de hernies paroxysmiques. 3. La succession des dommages causes par ictus que, selon Scholz, on rencontre generalement dans les cas d'epilepsie idiopathique, a ete legerement differente dans le cas que nous avons etudie; en effet, c'est la corne d'Ammon qui a ete le moins affectee. D'autre part, les modifications les plus graves ont ete constatees dans le cortex cerebelleux, le corps rhomboidal et, chose curieuse, dans le noyau rouge de Stilling. La predominance de dommages dans les structures mesencephaliques et cerebelleuses s'explique par le fait que, pour des raisons cliniques, les structures fonctionnelles du systeme des neurones du noyau rouge ont deja ete diagnostiquees comme responsables de ce type de petit mal. 4. La decouverte d'une migration inhibee dans le cortex cerebelleux nous semble significative pour expliquer la dependance du petit mal impulsif de l'ǎge du malade, ainsi qu'une serie d'anomalies de constitution et de croissance qui characterisent cette manifestation de la maladie. La question qui se pose est celle de savoir jusqu'a quel point de telles perturbations du developpement, qui sont trop peu importantes pour ětre decisives pour l'etiologie, pourraient former le profile de l'image clinique speciale.

Background/Aim. Dentate nucleus (nucleus dentatus) is the most distant of the cerebellar nuclei and the major system for information transfer in the cerebellum. So far, dendritic branches of four different kinds of large neurons of dentate nucleus, have been considered mainly qualitatively with no quantification of their morphological features. The aim of the study was to test the qualitative hypothesis that the human dentate nucleus is composed of various types of the large neurons by quantitative analysis of their dendritic branching patterns. Methods. Series of horizontal sections of the dentate nuclei were taken from 15 adult human brains, free of diagnosed neurological disorders. The 189 Golgi-impregnated images of large neurons were recorded by a digital camera connected to a light microscope. Dendritic branching patterns of digitized neuronal images were analyzed by modified Sholl and fractal analyses. Results. The number of intersections (Nm), critical radius (rc) and fractal dimension (D) of dendritic branching pattern for four types of the large neurons were calculated, statistically evaluated and analyzed. The results show that there is a significant difference between four neuronal types in one morphometric parameter at least. Conclusion. The present study is the first attempt to analyze quantitatively the dendritic branching pattern of neurons from the dentate nucleus in the human. The hypothesis that the four types of the large neurons exist in this part of human cerebellum is successfully supported.

The veins of the dentate nucleus are composed of several channels draining the external surface and one single vein draining the internal surface. We analyzed specimens of the human cerebellum and described the central vein of the nucleus dentatus as the main venous outflow of the nucleus. The central vein of the nucleus dentatus is formed by a network of smaller vessels draining the sinuosities of the gray matter; it emerges from the hilum of the nucleus and runs along the superior cerebellar peduncle, opening in the anterior vermian vein. We looked for this structure and for the surrounding veins on ultra-high-field (7 Tesla) MR, using susceptibility-weighted imaging. An anatomical and radiological description of the veins of the dentate nucleus is provided, with some remarks on the future clinical applications that these findings could provide.

In recent years, abnormal eye movements in patients with cerebellar disturbances are receiving the attention of many workers.We think that rebound nystagmus is an indication of these relationships and is one of the most representative of the cerebellar signs which cause abnormal eye movements. We treated 11 patients with Vertical Rebound Nystagmus (VRN) disected upwards following a rapid shift from downward gaze to forward gaze. This was confirmed by ENG. We conclude that rebound nystagmus is a form of intention tremor affecting eye movements.It appears only in bilateral disturbances of all these structurs nucleus dentatus and its efferent pathway (superior pedunculus), nucleus fastigii and vestibulo cerebellum.

Presentation of a new apparatus which allows the rapid performance – with great precision and a minimum of calculations – of several simultaneous penetrations of double sagittal and frontal obliquity, in a manner that is comfortable for both patient and surgeon. Furthermore, it should permit the approach of extra-encephalic structures: posterior percutaneous cordotomy (Hitchcock), intra-hypophyseal implantation or cryodestruction, for example.

An Hand von funf Beobachtungen nicht symmetrischer Spindel- und Rundzell-dysgenesien im inneren und auseren Dentatumvlies bei Neugeborenen wird der Genese dieser bisher noch nicht beschriebenen Fehlbildung nachgegangen. Die Entwicklung aus der Grenzzone zwischen ventrikularer und akzidentieller Matrix in enger raumlicher Beziehung zum Dentatum zur Zeit der Dentatumfaltelung, last sich nachweisen.

The idea that lesion of the nucleus dentatus may stop the pathological mechanism of Ramsey-Hunt disease led us to perform a dentatotomy in a female patient aged 28, who suffered from myoclonic movements for 6 years. Surgery was carried out by transtentorial approach from a burr hole in the right temporo-occipital region. The coagulation electrode was introduced first into the right nucleus dentatus; after its coagulation, myoclonic movements in the right extremities disappeared. For this reason, the left nucleus dentatus was also destroyed by introducing the electrode into the left side from the same right side burr hole through the midline. All myoclonic movements stopped at least transitorily.

The neurolipofuscin of the oliva inferior and nucleus dentatus has been investigated by means of histochemical, and light- and electron microscopical methods. The pigments of both nuclei contain hydrolytic enzymes and can be demonstrated by lipid stains. The PAS-reaction and the performic acid-aldehyde-fuchsin staining give different results. The pigment of oliva inferior is PAS-positive and gives a strong reaction with aldehydefuchsin or astrablue, the pigment of the nucleus dentatus, on the contrary, does not react at all or only faintly. On the electron microscopical level the two types of pigments differ in their shape, diameter, electron density, and composition. It is assumed, that the pigment of oliva inferior consists to a large extent of a sulfur containing melanin-like substance, which is linked with a PAS-positive autoxidised and polymerised lipid component. This compound is lacking in the pigment of the nucleus dentatus or is present only in small amounts.

SUMMARY Brain sections were studied from 34 infants who died following an episode of clinical hypoxia in the perinatal period. They were divided into two groups of 17 each depending on the additional presence or absence of a recorded episode of hypoglycaemia. Attention was confined mainly to alterations of the neurones in the grey matter. Histologically, both groups of infants, who had been exposed to essentially similar degrees of hypoxia, were characterised by the presence of ‘ischaemic’ nerve-cell change, the cells involved being shrunken with hyperchromatic cytoplasm and pyknotic nuclei. The distribution of these changes was similar, with predominant involvement of the brain-stem nuclei, dentate nucleus, thalamus and Ammon's horn. Involvement of the cerebral cortex was less common. The frequency and severity of these changes at the various sites differed slightly but not significantly between the two groups. It appears that in infants who suffer hypoxia in the newborn period, exposure to a limited degree of hypoglycaemia produces no histological evidence of central nervous system damage over and above that produced by the hypoxia. RESUME Des coupes cerebrales ont eteetudiees chez 34 nouveaux-nes morts a la suite d'un episode d'hypoxie clinique durant la periode neo-natale. Us ont ete divises en deux groupes de 17, selon la presence ou l'absence d'un episode associe et mis en evidence d'hypoglycemie. L'etude a ete concentree sur les alterations des neurones de la substance grise. Histologiquement, chez les deux groupes d'enfants, exposes au meme degre d'hypoxie, on a observe des modifications des cellules nerveuses de type ‘ischemique’, les cellules alterees etant retrecies avec un cytoplasme hyperchromatique et des noyaux pycnotiques. La repartition de ces modifications etait identique, predominant dans les noyaux du tronc cerebral, le noyau dentele, le thalamus et la come d'Ammon. L'atteinte du cortex cerebral etait moins frequente. La frequence et la gravite de ces modifications dans les differents sieges lesionnels presentaient des differences legeres mais non significatives entre les deux groupes. II semble done que l'exposition a un degre leger d'hypoglycemie pendant la periode neo-natale n'ajoute pas de lesions du systeme nerveux central a celles qui sont produites par une hypoxie concomittante. ZUSAMMENFASSUNG Es wurden Hirnschnitte von 34 Kindern untersucht, die in der Perinatalperiode nach einer Episode klinischer Hypoxie gestorben waren. In Abhangigkeit vom zusatzlichen Vorhandensein oder Fehlen einer registrierten Hypoglykamie wurden sie in zwei Gruppen von je 17 Kindern geteilt. In der Hauptsache lag das Interesse bei den Veranderungen der Neurone der grauen Hirnsubstanz. Beide Gruppen der Kinder, die einem grundsatzlich gleichen Ausmaβ von Hypoxie ausgestezt waren, waren histologisch charakterisiert durch eine ‘ischamische’ Nervenzellveranderung, bei der die Zellen geschrumpft sind und ein hyperchromatisches Zytoplasma und einen pyknotischen Kern aufweisen. Die Verteilung dieser Veranderungen war gleichmaβig, wobei die Hirnstammkerne, der Nucleus dentatus, der Thalamus und das Ammonshorn vorwiegend betroffen waren. Die Groβhirnrinde war seltener beteiligt. Die Haufigkeit und Schwere der Veranderungen an den verschiedenen Stellen differierten nur leicht und nicht significant zwischen den beiden Gruppen. Offenbar wird durch eine Hypoglykamie begrenzten Ausmaβes wahrend der Neugeborenenperiode der Schaden am ZNS, der durch eine gleichzeitige Hypoxie verursacht wird, nicht weiter vergroβert. RESUMEN Se estudiaron cortes de cerebro de 34 ninos que murieron tras un episodio de hipoxia clinica en el periodo perinatal. Fueron divididos en dos grupos de 17 segun hubiera o no un episodio de hipoglucemia. Se puso atencion especialmente en las alteraciones de las neuronas de la substancia gris. Histologicamente, ambos grupos de ninos que habian sido expuestos a grados de hipoxia esencialmente similares, se caracterizaron por la presencia de un cambio neuronal ‘isquemico’ con las celulas afectadas retraidas, con un citoplasma hipercromico y nucleos picnoticos. La distribucion de estos cambios era similar, con afectacion predominante de los nucleos del tronco, nucleo dentado, talamo y asta de Ammon. La afectacion del cortex cerebral era menos corriente. La frecuencia y gravedad de estos cambios en las diversas localizaciones diferia ligeramente, pero sin significacion entre los dos grupos.

Report of a case of histiocytosis X with adult onset, widespread skin lesions and rare central nervous system involvement resulting in dizziness and ataxia. On autopsy histiocytosis X infiltrates in the central nervous system were demonstrated with granuloma formation in the temporal lobe and nucleus dentatus of the cerebellum.

THE comments by Comfort on Dawkins's1 memory theory struck a sympathetic chord, late though they were received here. We failed to detect any of the changes claimed2 for the nucleus dentatus and found but a fraction3 of the neurones estimated. Counts covering newborn to presenescent age produced no age correlation in the human olivary nucleus4. The need for the provision of more cell counts stressed by Comfort was emphasized too by Blinkow5 at a recent meeting here. Neuronal population studies done by count are certainly more tedious than those based on general estimates. They render figures more like those of bankers than of economists. Delorenzo6 found no evidence for the loss of Purkinje cells in man reported by Ellis7. Thus not only for rodents, but in man too, the more recent studies based on larger material, fail to demonstrate loss of neurones with advancing age. Available information about the regular Purkinje cell layer is so contradictory, the multilayered cerebral cortex with cell number estimates ranging8,9 from 2.6 × 109 to 16.5 × 109, that it is even less likely to provide unequivocal data easily. The billion range is not of variability but one of uncertainty. Side by side illustrations demonstrating age changes suffer from what may be called the Kara Mustapha fallacy*. Recent work by Dayan10 raises doubts about some more tenets of the neuropathology of ageing. Dawkins's model of memory helps to bring to light the narrow base supporting neurone loss as an uncontestable axiom.