Congenital Hydrocephalus and Abnormal Subcommissural Organ Development in Sox3 Transgenic Mice

Congenital hydrocephalus (CH) is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage) of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles) is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO) a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF), a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner

The Socratic Method in Cognitive Behavioural Therapy: A Narrative Review

The Socratic Method has been described as an important component of CBT interventions yet an empirical case for its use has not been made. The objective of this paper is to review the role of the Socratic Method in CBT in four stages. First, a review of the literature describes how the Socratic Method is applied and defined within CBT, with assumptions regarding its proposed benefits identified. Second, a review of empirical literature demonstrates that multiple challenges to the evaluation of the Socratic Method exist and that no direct evidence supports the premise that it is beneficial in CBT. Evidence is examined which may suggest why the Socratic Method could be beneficial in therapy. Finally, the hypothesised function of the Socratic Method within therapy is discussed in reference to the Interacting Cognitive Subsystems framework. A number of avenues for future research are proposed in order to determine whether this potentially valuable therapeutic component contributes to the efficacy of CBT

Connatal (fetal) hydrocephalus - an acquired pathology?

We investigated the etiology of hydrocephalus present at birth, i.e. of fetal hydrocephalus. Both inherited and dysraphic major malformations are very rare. Intraventricular hemorrhages and viral infections during pregnancy are among the proposed etiologies; they are supported more by anatomical, physiopathological and experimental findings than by clinical evidence. Cases of fetal intraventricular hemorrhages cited in the literature are anecdotical, and the reports fail to identify maternal or fetal predisposing factors. The role of viruses in the etiology of connatal hydrocephalus has been postulated on the basis of epidemiological considerations in human pathology and of a considerable amount of experimental studies in animals. Investigations were generally focused on aqueduct ependyma, but research should also address other structures involved in the genesis of hydrocephalus (choroid plexus, extraventricular CSF pathways, including arachnoid villi). Furthermore, experimental evidence has emerged concerning a number of toxins and of drugs administered during pregnancy, which are thought to be involved in the genesis of hydrocephalus: once more, the conclusions reached in these experimental trials lend further credence to the human epidemiological data linking pregnancy disturbances with fetal hydrocephalus. Since most of these toxic agents are also thought to induce major malformations, we could assume the degree of their effect to depend on the embryonal stage affected: the earlier the action, the worse the malformatio