Mikaela Barresi

Cortical folding is a defining feature of mammalian brain evolution widely attributed to spatially patterned cell proliferation, neuronal differentiation, and migration that drive regional expansion of the cerebral cortex. Growth-centric models have dominated theories of gyrification for decades; however, cortical morphogenesis is not governed by expansion alone. In this hypothesis-driven review, we reconceptualize cell death as a potential driver of cortical folding. We synthesize evidence indicating that apoptosis is spatiotemporally regulated during healthy brain development, influences cortical size and structure when perturbed, and functions differently in cell type- and layer-specific contexts. Apoptosis has been largely overlooked as an instructive contributor to gyral and sulcal formation. We explore the possibility that spatially patterned apoptosis may directly modulate cell density, radial units, and cortical topology, acting in concert with, rather than a consequence of, proliferation and migration to sculpt the developing brain. We propose that this is a substantial area of investigation given the limited data on spatially patterned apoptosis and gyrification and the evidence that would be required to substantiate this hypothesis. Recognizing the potential for apoptosis as a candidate driver of gyrification expands current developmental models and provides a new testable framework for interpreting both evolutionary cortical expansion and malformations.

Neonatal brain injuries, such as stroke, cause focal ischaemic lesions that often result in lifelong neurological disabilities, yet effective treatments remain limited. Early-phase therapeutic screening requires models that can reliably reproduce injury severity while minimising confounding variables, including prolonged or variable anaesthesia, surgical stress, and invasive procedures that themselves affect injury progression. Existing models of neonatal focal ischaemia often exhibit high mortality, technical complexity, and substantial variability in lesion location and volume. As a result, there is a critical need for a rapid, ethically refined, and scalable neonatal model that produces consistent cortical injury suitable for screening neuroprotective, biomaterial-based, and regenerative therapies. We established a minimally invasive photothrombotic ischaemia model in postnatal day 10 rats by administering intraperitoneal Rose Bengal (25, 40, or 60 mg/kg) and activating it with a fixed 10-minute exposure to 565-nm light through the intact scalp and skull. This incision-free protocol allowed a total procedure duration of 19 min. We characterized dose-dependent effects on infarct volume and anatomical distribution, cortical atrophy, ventricular enlargement, apoptosis (cleaved caspase-3), astrocytic and microglial reactivity (glial fibrillary acidic protein, GFAP; ionized calcium-binding adapter molecule 1, Iba1), and sensorimotor outcomes (wire hang, cylinder rearing, adhesive tape removal) at 1, 7, and 14 days after injury. Additional analyses assessed the reproducibility of lesion size across litters and explored sex-specific differences. A 25 mg/kg dose induced a reliable and well-localized motor cortex infarct with no mortality. Higher doses of Rose Bengal produced proportionally larger infarcts with greater subcortical involvement and more pronounced secondary atrophy. Across all groups, apoptotic signalling and glial reactivity remained elevated through 14 days, indicating persistent tissue injury. Sensorimotor impairments were robust at all stages, with deficits in forepaw use, endurance, and tactile response correlating with lesion volumes in the 25 mg/kg group. No significant sex differences were observed for any histological or behavioural outcomes. This refined neonatal photothrombotic model provides a reproducible, simple, scalable, and ethically optimized platform for inducing severe focal cortical injury. The model’s stable injury territory, short, standardized procedure, and consistent functional readouts fill a major gap in current research tools and provide a practical foundation for early-phase testing of neuroprotective and regenerative interventions.

Introduction: Automatic exposure control (AEC) is a device used in radiographic practice which terminates a radiographic acquisition when a certain exposure threshold is reached. The AEC is commonly utilised for in‐bucky imaging, such as for the chest, abdomen, pelvis and spine. There are many benefits to utilising the AEC where awareness and knowledge of the technology are thoroughly understood. Poor technique when utilising the AEC, however, will alter dose, and by extension, image quality. This study aimed to assess how changes in patient positioning when using AEC for chest, abdomen, lumbar spine and pelvic x‐ray examinations affect patient dose and image quality? Methods: An anthropomorphic phantom was marked every 1 cm from the ideal centring point in each direction; superior, inferior, left lateral and right lateral, for up to 5 cm of off‐centring. Exposures were taken at each position and the tube current, air kerma and signal‐to‐noise ratios recorded for each exposure. Results: Air‐kerma changes ranged from a maximum reduction of 6.06%, 74.72%, 76.07%, and 35.66% for the chest, abdomen, pelvis and lumbar spine, respectively, to a maximum increased air kerma of 50.09%, 8.00% and 10.32% for the chest, pelvis and lumbar spine. The abdomen did not demonstrate any increased air‐kerma results. Statistically significant changes ( p < 0.05) to dose were observed in 54 of the 80 (67.5%) separate recordings. Changes to signal‐to‐noise ratio varied from a maximum negative change of 49.14% to a maximum positive change of 25.10%. Conclusion: Statistically significant differences in dose were commonly discovered for mis‐positioning beyond 1–2 cm, which will likely occur within the clinical environment. Such variation in dose and signal‐to‐noise ratio identifies potential impacts to image quality and dose burdens to patients. The results highlight the need for careful consideration when using the AEC and the requirement for accurate positioning technique by the radiographer.

The size and shape of the cerebral cortex have changed dramatically across evolution. For some species, the cortex remains smooth (lissencephalic) throughout their lifetime, while for other species, including humans and other primates, the cortex increases substantially in size and becomes folded (gyrencephalic). A folded cortex boasts substantially increased surface area, cortical thickness, and neuronal density, and it is therefore associated with higher-order cognitive abilities. The mechanisms that drive gyrification in some species, while others remain lissencephalic despite many shared neurodevelopmental features, have been a topic of investigation for many decades, giving rise to multiple perspectives of how the gyrified cerebral cortex acquires its unique shape. Recently, a structurally unique germinal layer, known as the outer subventricular zone, and the specialized cell type that populates it, called basal radial glial cells, were identified, and these have been shown to be indispensable for cortical expansion and folding. Transcriptional analyses and gene manipulation models have provided an invaluable insight into many of the key cellular and genetic drivers of gyrification. However, the degree to which certain biomechanical, genetic, and cellular processes drive gyrification remains under investigation. This review considers the key aspects of cerebral expansion and folding that have been identified to date and how theories of gyrification have evolved to incorporate this new knowledge.