To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH.

Background A multi-user competitive game within the virtual world Second Life for undergraduate radiology learning was adapted for team participation. This study aimed to assess student perception, impact on learning, and eventual correlation of game results with post-exposure tests and course grades. Methods The game consisted of six weekly stages, dedicated to thoracic, abdominal, and musculoskeletal radiological anatomy and semiology. Participants had several days a week to review self-guided radiology educational content and then complete individual multiple-choice tests and solve team tasks to progress through the game's ranking. Additionally, they completed a cognitive load test, a questionnaire about the experience and a post-exposure knowledge test. Results Fifty-two students organised into 13 teams participated in the game and assessed different aspects of the experience with a mean score ≥ 7.8 on a 10-point scale, highlighting the participation of the teacher (9.3 ± 1.1), the educational contents (8.8 ± 1.4) and the usefulness for their education (8.7 ± 1.4). Participants obtained better post-exposure test results (p < 0.007) and better course grades (p < 0.021) than non-participants did. Conclusion A multi-user game adapted to team competition to learn radiology in Second Life was very positively perceived by third-year medical students, who highly valued its content, organisation, and usefulness for their training. Most of the participants agreed that they had collaborated as a team and that playing in competitive environments helps them learn better. The best post-exposure and academic results compared to non-participating students indicate the potential impact of the game on learning.

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Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.