Sensitivity of Purkinje cell dendrites to glutamic acid

Summary The distribution of glutamate sensitive sites was studied in vitro in thin cerebellar sections from guinea-pigs, in which Purkinje cell bodies and some of the principal dendrites were identified microscopically. Glutamate administered near the cell body induced firing. Stronger excitation, however, was produced when glutamate was administered to the molecular layer along a strip of tissue extending from the soma of the cell under study towards the pial surface of the slice. Excitation induced by glutamate slowly declined in some cells during prolonged administration. D-Glutamate was a weaker excitant than the L-isomer. These results suggest that the dendrite of the Purkinje cell is more sensitive to glutamate than the cell soma.     

Perturbed step initiation in cerebellar subjects 1. Modifications of postural responses

Recent experiments in healthy subjects have demonstrated that automatic postural responses can be suppressed when subjects are instructed to step instead of maintain stance in response to the surface translation. The aim of the present study was to investigate the role of the cerebellum in coordinating this interaction between the central command to step and peripherally triggered automatic postural responses. Eight subjects with cerebellar degeneration and eight control subjects were instructed to either maintain stance or step forward in response to a backward translation. In order to determine whether prediction of perturbation amplitude assisted suppression of postural responses, three platform translations were presented in both a serial (predictable) and a random (unpredictable) order. Cerebellar subjects were able to suppress their initial postural responses to the same amount as control subjects when instructed to step forward in response to backward translations, despite their hypermetria and inability to scale responses to predictable perturbation amplitudes. Control, but not cerebellar, subjects scaled the size of their postural responses to predictable perturbation amplitudes. The perturbation amplitude, however, had no effect on the size of early automatic responses when they were suppressed by instruction to step. The size of the suppressed postural response was independent of predictability of perturbation amplitudes in both control and cerebellar subjects. The dynamic interaction between automatic postural responses to an external perturbation and anticipatory postural adjustments for step initiation seems independent of prediction of perturbation amplitude and the integrity of the cerebellum. Although cerebellar subjects show larger-than-normal magnitude and variability of postural responses and an inability to scale the size of responses to predictable perturbation amplitudes, the cerebellum does not seem to be critical for suppression of the early postural response with a centrally intended movement. Received: 2 September 1996 / Accepted: 18 August 1997     

Timing of onset of afferent responses and of use of kinesthetic information for control of movement in normal and cerebellar-impaired subjects

A coordinated triggering task requiring use of kinesthetic information was employed to assess the timing of use of kinesthetic information in normal subjects and patients with cerebellar dysfunction. Passive movements of varying velocity were imposed in the flexor direction about the metacarpophalangeal joint of the right index finger. Subjects attempted to depress a switch with their left thumb when the index finger moved, past a specified angle that was learned during a training session. The velocities ranged from 10°/s to 88°/s in 2°/s increments. After 200 trials, subjects were then instructed instead to react as quickly as possible (reaction-time task) to the onset of movement for an additional 200 trials. For the same movements, the timing of onset of responses of muscle spindle afferents and cutaneous mechanoreceptors was determined by recording the responses of these afferents using microneurography. For slow velocities, patients were able to perform similarly to normals but at faster velocities patients triggered too late compared with normals. Patients required more time to use kinesthetic information than did normal subjects. An estimate of kinesthetic processing was not longer in patients. The chief explanation for the prolonged time required to use kinesthetic information in patients was that their reaction times were prolonged by 93 ms. In addition, the movement time was also prolonged, but this accounted for only 23 ms. Impaired motor performance in tasks requiring the use of kinesthetic information in cerebellar patients can be explained largely by their prolonged reaction times. Muscle spindle afferents responded on average much sooner than cutaneous mechanoreceptors. Because of the limited time available to perfomr the kinesthetic triggering task, the role for cutaneous mechanoreceptors, to provide singals for on-line coordination of movement appears limited compared with muscle spindle afferents.     

Damage of purkinje cell axons following chronic phenytoin administration: An animal model of distal axonopathy

Summary An animal model of central distal axonopathy following chronic administration of phenytoin is described. Male C57/BL6J mice received diphenylhydantoin (DPH) in the daily diet (liquid diet Stardit, supplemented with vitamins) over a period of 8 weeks. Control and experimental animals were pair-fed.Twelve mice of both groups were perfused via the left ventricle with glutaraldehyde. Representative samples of the cerebral cortex (area 3), cerebellum (vermis and deep cerebellar nuclei), thalamus, hypothalamus, and liver were embedded in araldite. Semithin sections and electron microscopy of the cerebellar vermis revealed marked dystrophic changes in the Purkinje cell axons. The presynaptic segments of Purkinje cell axons in the deep cerebellar nuclei showed massive enlargement and swelling due to accumulation of spherical particles and tubular structures in the axoplasm. These structures represent a proliferation of the smooth endoplasmic reticulum.Identical changes were found in hepatocytes of treated animals. Because phenytoin induces hepatic microsomal enzymes, we suggest that phenytoin-related Purkinje cell damage may be produced by an induction of Purkinje cell microsomes with proliferation of the smooth endoplasmic reticulum which causes a swelling and enlargement of presynaptic segments of Purkinje cell axons in deep cerebellar nuclei. Chronic phenytoin administration to mice is a new model of phenytoin-induced encephalopathy and of distal axonopathy of cerebellar neurons.Supported by the Deutsche ForschungsgemeinschaftPresented in Part at the Joint Meeting of the German and Scandinavian Neuropathologists, Turku, Finland, June 3–4, 1983     

Damage and repair of the immature rat cerebellum after cis-dichlorodiammineplatinum II (cis-DDP) treatment. An ultrastructural study

Summary The aim of this electron microscopy study was to further investigate the effects of cis-dichlorodiammineplatinum (cis-DDP) on the cerebellum of the immature rat. Ten-day-old animals were treated with cis-DDP subcutaneously and killed after 1, 7, 15 or 21 days. On postinjection day 1, cis-DDP effects were evident mainly in the external granular layer, with nuclear damage in many dividing cells, while their cytoplasm appeared to be less affected. Some binucleate cells were also present. On the contrary, in postmitotic or more differentiated cells, only cytoplasmic alterations were found. At later stages (postinjection day 7), the frequency of damaged cells in the external granular layer decreased, but there was a cellular deficit in the internal granular layer. Many postmitotic neurons underwent coagulative necrosis. Finally (postinjection days 15 and 21), the cellular deficit was partly compensated for by reactive structures, e.g., glial cell fibers, which underwent hypertrophy after initial edema. Moreover, packing densities of Bergmann astrocytes and oligodendrocytes were higher.This study is a part of the scientific exchange program Proliferation and differentiation of normal and tumor cells between the Italian National Research Council and the Czechoslovak Academy of Sciences     

急性后颅窝血肿的微创穿刺术治疗

目的：探讨应用IL－2型特种针进行微创穿刺术治疗后颅窝血肿的可行性及临床应用。材料及方法：回顾性分析我们自1995年9月至1999年9月对28例后颅窝高血压性或外伤性脑内血肿及硬膜外血肿进行微创穿刺引流治疗的病例。结果：28例病例中除1例于穿刺成功后死于脑干功能衰竭外,其余病例均获成功,病人无后遗症,痊愈出院,其中1例伴发再出血,经血肿腔内止血药冲洗引流治疗再出血停止,结论：此穿刺针特点为针钻一体,解决了针在颅骨上固定问题,也解决了立体定向不能留置针管问题,微创穿刺方法治疗后颅窝血肿可避免传统后颅窝开颅手术,安全性高,疗效良好,操做简便,费用较低,易于在各级医院普遍开展,具有较大推广使用价值。     

Specific cerebellar reductions in children with chromosome 22q11.2 deletion syndrome

Children with chromosome 22q11.2 deletion syndrome commonly are found to have morphological brain changes, cognitive impairments, and elevated rates of psychopathology. One of the most commonly and consistently reported brain changes is reduced cerebellar volume. Here, we demonstrate that, in addition to the global cerebellum reductions previously reported, volumetric reductions of the anterior lobule and the vermal region of the neo-cerebellum in the mid-sagittal plane best differentiate children with the deletion from typically developing children. These results suggest that the morphological changes of specific portions of the cerebellum may be an important underlying substrate of cognitive impairments and increased incidence of psychopathology in this group.     

Expression of the axon growth-related neural adhesion molecule TAG-1/axonin-1 in the adult mouse brain

 TAG-1/axonin-1 is a neuronal cell adhesion molecule of the immunoglobulin superfamily. It is predominantly expressed during neural development and has been reported to be involved in axonal growth and pathfinding. Here, the expression of TAG-1/axonin-1 was investigated anatomically in the adult mouse brain by in situ hybridization using digoxigenin-labeled cRNA probes. Low levels of TAG-1/axonin-1 could be detected in cerebellar granule cells, in tufted and mitral cells of the olfactory bulb, and in pyramidal cells of area CA1 and CA3 of the hippocampus. We suspect that the expression of TAG-1/axonin-1 in these structures of the adult brain may serve neural plasticity. Accepted: 8 September 1997     

Serotonergic inhibition of the mossy fibre—granule cell glutamate transmission in rat cerebellar slices

Summary The glutamatergic mossy fibre granule cell pathway has been investigated in rat cerebellar slices. Exposure to 35 mM KCI, a concentration of K⁺ known to elicit Ca²⁺-dependent releases of excitatory amino acids from cerebellar slices, raised cGMP levels. The cGMP response was decreased in a concentration-dependent manner by D-(–)-2-amino-5-phosphonopentanoic acid (D-AP5) and by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) indicating the involvement of ionotropic glutamate receptors of both the N-methyl-D-aspartate (NMDA) and the non-NMDA type. The K⁺-evoked production of cGMP was potently inhibited (EC₅₀ = 1.21 nM) by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT₂ receptor agonist. The effect of DOI (0.01 M) was antagonized by 0.03 M of the 5-HT₂ receptor antagonists ketanserin and methiothepin. At concentrations higher than 0.1 M, both antagonists increased on their own the cGMP response elicited by high-K⁺. This effect was insensitive to tetrodotoxin.It had been previously shown that rat mossy fibre endings release glutamate upon depolarization and that such release can be inhibited by activation of 5-HT₂ receptors sited on the mossy fibre endings. Altogether the available data suggest the following conclusions: (a) the glutamate/aspartate endogenously released in cerebellar slices during K⁺ depolarization increase cGMP synthesis through the activation of both NMDA and non-NMDA receptors; (b) a portion of the cGMP response can be prevented by 5-HT₂ receptor activation and may reflect the activity of the mossy fibre-granule cell pathway. Thus serotonin is likely to exert a potent inhibitory control of the excitatory mossy fibre input to the cerebellum by acting at receptors of the 5-HT₂ type. Correspondence to M. Raiteri at the above address