Genetics of human hydrocephalus

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions

In a case of longstanding low vision regions of visual cortex that respond to tactile stimulation of the finger with Braille characters are not causally involved in the discrimination of those same Braille characters

Braille reading and other tactile discrimination tasks recruit the visual cortex of both blind and normally sighted individuals undergoing short-term visual deprivation. Prior functional magnetic resonance imaging (fMRI) work in patient 'S', a visually impaired adult with the rare ability to read both highly magnified print visually and Braille by touch, found that foveal representations of S's visual cortex were recruited during tactile perception, whereas peripheral regions were recruited during visual perception. Here, we test the causal nature of tactile responses in the visual cortex of S by combining tactile and visual psychophysics with repetitive transcranial magnetic stimulation. First, we replicate the previous fMRI findings in S. Second, we demonstrate that transient disruption of S's foveal visual cortex has no measurable impact on S's tactile processing performance compared to that of healthy controls - a pattern not predicted by the fMRI results. Third, stimulation of foveal visual cortex maximally disrupted visual processing performance in both S and controls, suggesting the possibility of preserved visual processing within S's foveal representation. Finally, stimulation of somatosensory cortex induced the expected disruption to tactile processing performance in both S and controls. These data suggest that tactile responses in S's foveal representation reflect unmasking of latent connections between visual and somatosensory cortices and not behaviourally relevant cross-modal plasticity. Unlike studies in congenitally blind individuals, it is possible that the absence of complete visual loss in S has limited the degree of causally impactful cross-modal reorganisation