p75NTR independent oligodendrocyte death in cuprizone-induced demyelination in C57BL/6 mice

Feeding C57Bl/6 J mice the copper chelator cuprizone leads to selective apoptosis of mature oligodendrocytes and concomitant demyelination predominantly in the corpus callosum. The process of oligodendrocyte apoptosis in this animal model for multiple sclerosis (MS) involves early microglial activation, but no infiltration of T-lymphocytes. Therefore, this model could mimic early stages of oligodendrocyte degeneration Affected oligodendrocytes express the common neurotrophin receptor, p75(NTR), a 'stress-receptor' which under certain circumstances can induce apoptosis. Only affected oligodendrocytes in MS lesions and MS animal models express this receptor. In order to study the significance of p75(NTR) in the fate of oligodendrocytes, we have exposed wild-type as well as p75(NTR)-knockout mice to a 0.2% (w/w) cuprizone diet and performed a comparative immunohistochemical analysis of the corpus callosum at various time points. Surprisingly, our results show that the absence of p75(NTR) did not alter cuprizone-induced oligodendrocyte death (and subsequent de- or remyelination). Apparently, intracellular apoptosis pathways in adult oligodendrocytes do not require p75(NTR) activated signal transduction in the absence of T-lymphocytes and T-lymphocyte derived cytokines.     

Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease

Morphological alterations in microvasculature occur as a common finding in the brains of non-demented aged persons and patients with Alzheimer's disease. Quantifying the extent of this vascular pathology, however, has been complicated by systematic error (bias) associated with the applications of assumption- and model-based morphometric techniques to human and animal tissues. The current study used novel assumption- and model-free stereological approaches to quantify capillary parameters in the corpus callosum of a double amyloid precursor protein/presenilin-1 transgenic murine model of Alzheimer's disease. The results revealed significant reductions in the total number of capillary segments in white matter of transgenic mice compared to non-transgenic littermates, with no differences in total capillary length. These findings support the view that the expression of mutant human genes for beta-amyloid peptides alters the normal architecture of cerebral capillary vessels in the white matter of mouse brain, which may model microvasculature changes reported in Alzheimer's disease.     

Reversible cytotoxic edema in the splenium of the corpus callosum related to antiepileptic treatment: report of two cases and literature review

PURPOSE: Clinically silent lesions localized in the splenium of the corpus callosum (SCC) are a rare finding in the magnetic resonance imaging (MRI) of patients receiving antiepileptic drugs (AEDs). They are usually of benign character but may induce unnecessary complementary examinations if their nature is unrecognized. So far, 22 cases have been described in the literature, for which different etiologies have been proposed. We describe two further cases and discuss the probable lesion etiology. METHODS: We report two cases including a 25-year-old male patient and a 12-year-old female patient with a transient SCC lesion discovered in the context of a presurgical epilepsy evaluation. RESULTS: Comprehensive MRIs, including diffusion tensor imaging-based fiber tracking of the lesion, revealed a cytotoxic edema not disrupting neuronal fibers. Serum arginine vasopressin (AVP) measurements revealed an altered secretion during the acute phase in one patient. CONCLUSIONS: On the basis of our results, we hypothesize that the lesion consists of a cytotoxic edema, possibly induced by abrupt AED concentration changes and associated to alterations of AVP secretion.     

Cellular and molecular tunnels surrounding the forebrain commissures of human fetuses

Glial cells and extracellular matrix (ECM) molecules surround developing fiber tracts and are implicated in axonal pathfinding. These and other molecules are produced by these strategically located glial cells and have been shown to influence axonal growth across the midline in rodents. We searched for similar cellular and molecular structures surrounding the telencephalic commissures of fetal human brains. Paraffin-embedded brain sections were immunostained for glial fibrillary acidic protein (GFAP) and vimentin (VN) to identify glial cells; for microtubule-associated protein-2 (MAP-2) and neuronal nuclear protein (NeuN) to document neurons; for neurofilament (NF) to identify axons; and for chondroitin sulfate (CS), tenascin (TN), and fibronectin (FN) to show the ECM. As in rodents, three cellular clusters surrounding the corpus callosum were identified by their expression of GFAP and VN (but not MAP-2 or NeuN) from 13 to at least 18 weeks postovulation (wpo): the glial wedge, the glia of the indusium griseum, and the midline sling. CS and TN (but not FN) were expressed pericellularly in these cell groups. The anterior commissure was surrounded by a GFAP+/VN+ glial tunnel from 12 wpo, with TN expression seen between the GFAP+ cell bodies. The fimbria showed GFAP+/VN+ cells at its lateral and medial borders from 12 wpo, with pericellular expression of CS. The fornix showed GFAP+ cells somewhat later (16 wpo). Because these structures are similar to those described for rodents, we concluded that the axon guiding mechanisms postulated for commissural formation in nonhuman mammals may also be operant in the developing human brain.     

Comprehension of humor in primary agenesis of the corpus callosum

Individuals with agenesis of the corpus callosum (ACC) can, in some cases, perform normally on standardized intelligence tests. Nevertheless, recent studies suggest that individuals with ACC and normal IQ scores have deficits in domains of fluid and social intelligence. Anecdotal reports from families suggest diminished appreciation of the subtleties of social interactions, and deficits in the comprehension of jokes and stories. In this research, both the cartoon and narrative joke subtests of a humor test (developed by Brownell et al. [Brownell, H., Michel, D., Powelson, J., & Gardner, H. (1983). Surprise but not coherence: sensitivity to verbal humor in right-hemisphere patients. Brain and language, 18(1), 20-27] and Bihrle et al. [Bihrle, A. M., Brownell, H. H., Powelson, J. A., & Gardner, H. (1986). Comprehension of humorous and non-humorous materials by left and right brain-damaged patients. Brain and Cognition, 5(4), 399-411]) were given to 16 adults with complete ACC (all with IQs>80) and 31 controls of similar age and IQ. Individuals with ACC performed worse than controls on the narrative joke subtest (p<.025) when VIQ was controlled. However, on the cartoon subtest the two groups were not significantly different. Covarying age, forms of IQ, narrative memory, set-switching, and literal language comprehension did not substantially alter the group difference. However, covarying comprehension of nonliteral language and proverbs eliminated the difference, suggesting a common origin for the comprehension of jokes, nonliteral language, and proverbs, most likely related to capacity for understanding second-order meanings.     

The effects of redundant stimuli on visuospatial processing in developmental dyslexia

The interhemispheric deficit theory of dyslexia postulates that reading difficulties can arise from abnormal communication/collaboration between the cerebral hemispheres. A currently popular way to gather information about interhemispheric processing and integration is with the redundant stimuli task, where participants respond to stimuli presented to the left visual field, right visual field, or both visual fields simultaneously. In neurologically normal individuals, response times to bilateral simple stimulus presentations are faster than response times to a single stimulus in either visual field alone (referred to as redundancy gain). In contrast, individuals with no corpus callosum exhibit greater redundancy gains than would be expected by probability summation. In the present study, 11 children with phonological dyslexia showed a similar "over violation" of the probability (race) model when responding with the left but not the right hand. This asymmetry was not found in age- and IQ-matched control children. The results are at least partially consistent with the notion of phonological dyslexia involving deficits in the transfer of information across the corpus callosum.     

Investigation of the mechanism of nicotine induced relaxation in rabbit corpus cavernosum in vitro

In order to determine whether nicotine acts on corporal smooth muscle, the mechanism of its effect on strips of rabbit corpus cavernosum was studied in vitro. Rabbit corpus cavernosum muscle strips were mounted in an organ bath with modified Krebs-Henseleit solution and aerated with 95% O₂ and 5% CO₂. Tension was measured with isometric force transducers, and muscle relaxation was expressed as the percent decrease of precontraction induced by phenylephrine. Nicotine produced concentration dependent relaxation when preparations were precontracted by phenylephrine (10^–5 M). The maximum nicotine-induced relaxation was 60.4±4.2% of the phenylephrine contraction and was not affected by indomethacin (10^–5 M), N^w-nitro L-arginine methyl ester (3×10^–5 M), methylene blue (10^–5 M), glibenclamide (10^–5 M), clotrimazole (10^-6 M), tetraethylammonium (3×10^–4 M), or 4-aminopyridine (10^–3 M). Nicotine did not exhibit a calcium antagonizing effect. From these results, we conclude that nicotine-induced relaxation of the rabbit corpus cavernosum is not mediated by the release of nitric oxide, prostaglandins or a related substance, by the activation of potassium channels, or by the stimulation of nicotinic cholinoceptors. Further work is needed to determine the cellular mechanism(s) of the action by which nicotine acts on corporal smooth muscle.     

Phagocytosis of<Emphasis Type="Italic"> Escherichia coli</Emphasis> by amoeboid microglial cells in the developing brain

Amoeboid microglial cells (AMC) in the corpus callosum of 1-day-old rats receiving a single intracerebral injection of Escherichia coli (E. Coli) were examined at various time intervals following the injection. A large number of E. coli were internalized by the AMC at 1–3 h after the injection. However, no E. coli were identifiable at 1 day after the injection, but large phagosomes were observed in the cytoplasm of AMC. With time, the phagosomes in the AMC were reduced so that by 7 days the cells appeared comparable to the controls. Apoptotic or necrotic AMC were not encountered during the study period. This is consistent with the results of cell counts, which showed no significant change in the AMC population following E. coli injection compared with controls. The present results suggest that AMC are capable of removing live bacteria from their vicinity. Up-regulation of complement type 3 receptors and induction of major histocompatibility complex class II antigens were observed in the AMC at days 1–3 and 7 following E. coli administration. This may be related to their involvement in mediating endocytosis and their possible role in antigen presentation.     

Effective binocular integration at the midline requires the corpus callosum

To study the role of the corpus callosum (CC) in midline binocular integration, the effects of late callosotomy and congenital CC agenesis on the ability to perceive dichoptic plaid motion was assessed. Coherent motion was well perceived at all locations in the visual field under dioptic viewing but not along the vertical meridian (VM) when the components were dichoptically presented. This deficit was totally abolished in the agenesis subject and reduced in the callosotomized individual when stimulus size was increased beyond the VM. Electrophysiological correlates were also examined by recording visual evoked potentials and these showed that the P1/N2 components were abnormal for small dichoptic stimuli presented on the midline. These findings attest to the importance of the contribution of CC to midline binocular integration and the effects of cerebral plasticity.     

Pituitary duplication associated with oral dermoid and corpus callosum hypogenesis

We report a case of pituitary duplication in a neonate girl whose magnetic resonance (MR) images showed unusual findings of hypogenesis of the corpus callosum and oral dermoid. Pituitary duplication is an extremely rare malformation, with only a few previously reported cases. It occurs most commonly in association with complicated midline and skull base anomalies. We present a case of this malformation with special emphasis on the hypogenesis of splenium of the corpus callosum and oral dermoid.