Underdevelopment of the Human Hippocampus in Callosal Agenesis: An In Vivo Fetal MRI Study.

BACKGROUND AND PURPOSE: In subjects with agenesis of the corpus callosum, a variety of structural brain alterations is already present during prenatal life. Quantification of these alterations in fetuses with associated brain or body malformations (corpus callosum agenesis and other related anomalies) and so-called isolated cases may help to optimize the challenging prognostic prenatal assessment of fetuses with corpus callosum agenesis. This fetal MR imaging study aimed to identify differences in the size of the prenatal hippocampus between subjects with isolated corpus callosum agenesis, corpus callosum agenesis and other related anomalies, and healthy controls. MATERIALS AND METHODS: Eighty-five in utero fetal brain MR imaging scans, (20-35 gestational weeks) were postprocessed using a high-resolution algorithm. On the basis of multiplanar T2-TSE sequences, 3D isovoxel datasets were generated, and both hippocampi and the intracranial volume were segmented. RESULTS: Hippocampal volumes increased linearly with gestational weeks in all 3 groups. One-way ANOVA demonstrated differences in hippocampal volumes between control and pathologic groups (isolated corpus callosum agenesis: left, P = .02; right, P = .04; corpus callosum agenesis and other related anomalies: P < .001). Differences among the pathologic groups were also present for both sides. Intracranial volume and right and left hippocampal volume ratios were different between corpus callosum agenesis cases and controls (P < .001). When we corrected for intracranial volume, no differences were found between corpus callosum agenesis and other associated anomalies and isolated corpus callosum agenesis (left, P = .77; right, P = .84). Hippocampal size differences were more pronounced at a later gestational age. CONCLUSIONS: Callosal agenesis apparently interferes with the normal process of hippocampal formation and growth, resulting in underdevelopment, which could account for certain learning and memory deficits in individuals with agenesis of the corpus callosum in later life.

Suppression of Smad-1 mRNA expression level by Smad-2 likely control dichotomy of NF-κB and Smads mediated activation.

The aim of this study was to find out how NF-κB and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs. In wild type cells no significant activation of NF-κB was observed while genetically modified cells exhibited somewhat different pattern of NF-κB activation depending on the Smad constructs combination used. The absence of NF-κB activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-κB and Smads mediated signaling pathways. The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-κB and Smads mediated pathways.

Involvement of the cranial nerves and their nuclei in spinocerebellar ataxia type 2 (SCA2).

Although the cranial nerves, their nuclei and related fiber tracts are crucial for a variety of oculomotor, somatomotor, somatosensory, auditory, vestibular-related, autonomic and ingestion-related functions, knowledge regarding the extent of their involvement in spinocerebellar ataxia type 2 (SCA2) patients is incomplete. Accordingly, we performed a pathoanatomical analysis of these structures in six clinically diagnosed SCA2 patients. Unconventionally thick serial sections through the brainstem stained for lipofuscin pigment (aldehyde-fuchsin) and Nissl material (Darrow red) showed that all oculomotor, somatomotor, somatosensory, auditory, vestibular and autonomic cranial nerve nuclei may undergo neurodegeneration during SCA2. Similarly, examination of myelin-stained thick serial sections revealed that nearly all cranial nerves and associated fiber tracts may sustain atrophy and myelin loss in SCA2 patients. In view of the known functional role of the affected cranial nerves, their nuclei and associated fiber tracts, the present findings provide appropriate pathoanatomical explanations for some of the disease-related and unexplained symptoms seen in SCA2 patients: double vision, gaze palsy, slowing of saccades, ptosis, ingestion-related malfunctions, impairments of the optokinetic nystagmus and the vestibulo-ocular reaction, facial and tongue fasciculation-like movements, impaired centripetal transmission of temperature-related information from the face, dystonic posture of the neck, as well as abnormalities of the brainstem auditory evoked potentials.

Spinocerebellar ataxias types 2 and 3: degeneration of the pre-cerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum.

The pre-cerebellar nuclei act as a gate for the entire neocortical, brainstem and spinal cord afferent input destined for the cerebellum. Since no pathoanatomical studies of these nuclei had yet been performed in spinocerebellar ataxia type 2 (SCA2) or type 3 (SCA3), we carried out a detailed postmortem study of the pre-cerebellar nuclei in six SCA2 and seven SCA3 patients in order to further characterize the extent of brainstem degeneration in these ataxic disorders. By means of unconventionally thick serial sections through the brainstem stained for lipofuscin pigment and Nissl material, we could show that all of the pre-cerebellar nuclei (red, pontine, arcuate, prepositus hypoglossal, superior vestibular, lateral vestibular, medial vestibular, interstitial vestibular, spinal vestibular, vermiform, lateral reticular, external cuneate, subventricular, paramedian reticular, intercalate, interfascicular hypoglossal, and conterminal nuclei, pontobulbar body, reticulotegmental nucleus of the pons, inferior olive, and nucleus of Roller) are among the targets of both of the degenerative processes underlying SCA2 and SCA3. These novel findings are in contrast to the current neuropathological literature, which assumes that only a subset of pre-cerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the pre-cerebellar nuclei separates all three phylogenetically and functionally defined regions of the cerebellum, impairs their physiological functions and thus explains the occurrence of gait, stance, limb and truncal ataxia, dysarthria, truncal and postural instability with disequilibrium, impairments of the vestibulo-ocular reaction and optokinetic nystagmus, slowed and saccadic smooth pursuits, dysmetrical horizontal saccades, and gaze-evoked nystagmus during SCA2 and SCA3.

Can the occurrence of bronchial asthma in potroom workers be prevented?

Bronchial reactivity was evaluated in a group of 35 workers at preemployment examination using the metacholine test. Three workers showed an increased bronchial reactivity, the rate being in accordance with the previous experience. Ten randomly chosen subjects with normal reactivity, who were engaged as potroom workers, were followed up during a two-to-five-year period. None of them experienced any significant respiratory complaints and their bronchial reactivity also remained normal. Only one worker had a borderline finding (PD20FEV1). Although selection at preemployment medical examination is a measure that has to be used only exceptionally, based on the finding obtained by non-specific bronchoprovocation challenge it seems that it can be recommended in the case of that particular exposure.