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Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

Background: Optic pathway glioma (OPG) is a feared complication to neurofibromatosis type 1 (NF1) since it can cause visual impairment in young children. The main goal of screening is to detect symptomatic OPGs that require treatment. Optical coherence tomography (OCT) has been suggested as a tool for detection of neuro-retinal damage. Aims: To investigate whether the ganglion cell layer assessed by OCT is a reliable measure to identify and detect relapses of symptomatic OPGs in children with NF1. Methods: Children (3–6 years) with NF1, with and without known OPG and children with sporadic OPG (S-OPG) resident in the Stockholm area, were invited and followed in a prospective study during a three-year period. Brain magnetic resonance tomography (MRI) had been performed in children with symptoms of OPG. Outcome measures were VA in logMAR, visual field index (VFI), average thicknesses of the ganglion cell-inner plexiform layer (GC-IPL), and peripapillary retinal nerve fiber layer (pRNFL). Results: There were 25 children with MRI-verified OPG and 52 with NF1 without symptomatic OPG. Eyes from NF1 patients without symptoms of OPG showed significantly better results in all four analyzed parameters compared to eyes with NF1-associated OPG. Mean GC-IPL measurements seemed stable and reliable, significantly correlated to pRNFL (correlation coefficient (r) = 0.662, confidence interval (CI) =.507 to.773 p<0.001), VA (r = -0.661, CI = -7.45 to -.551, p<0.001) and VFI (r = 0.644, CI =.452 to.774, p<0.001). GC-IPL measurements were easy to obtain and acquired at considerably younger age than pRNFL (5.6±1.5 vs 6.8±1.3; p<0.001). Conclusions: The mean GC-IPL thickness could distinguish well between eyes with OPG and eyes without symptomatic OPG in children with NF1. As thinning of GC-IPL assessed with OCT could indicate underlying OPG, it should be included in the screening protocol of children with questionable VA measurements and in particular in children with NF1. [ABSTRACT FROM AUTHOR]

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7-10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxic-ischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development.

Background: Survivors of pediatric brain tumors are at high risk of late complications that may affect their daily life in both short‐ and long‐term perspectives. Methods: In this nationwide registry‐based study we explored the occupational outcomes, including employment, sickness or activity compensation and parental leave, in 452 individuals in Sweden, born 1988–1996, and diagnosed with a brain tumor before their 15th birthday. Their results were compared with 2188 matched controls. Results: There were significant differences between cases and controls for all assessed variables. The cases had benefitted from sickness or activity compensation 11 times more often than controls (CI 7.90–15.83; p < 0.001) between 2005 and 2016. Controls were almost three times more likely to have an employment (OR 0.36; CI 0.28–0.47; p < 0.001) and nearly twice as likely to have been on parental leave (OR 0.56; CI 0.39–0.80; p = 0.002). Although cases treated for high‐grade tumors typically fared worse than those treated for low‐grade tumors, significant differences for all assessed variables were also observed for cases treated for a low‐grade tumor compared with controls. Conclusions: Our findings emphasize the need for follow‐up programs for all brain tumor diagnoses, not only those known to be at most risk. This is evident, for example, from the high number of cases who received sickness or activity compensation. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals treated for brain tumors in childhood are at high risk of cognitive and other late complications. The aim of this nationwide registry study was to explore further education following the nine years of compulsory school in Sweden in teenagers and young adults treated for childhood brain tumors. Individuals treated for embryonal tumors, low grade astrocytomas, optic pathway gliomas, craniopharyngiomas, and neuronal and mixed neuronal–glial tumors, were analyzed separately. All individuals treated for brain tumors were compared to about five times as many matched controls without cancer diagnoses or treatments. Our results demonstrate significant differences between cases and controls regarding attendance in high school, folk high school, and university. Individuals treated for embryonal tumors or optic pathway gliomas attended post-compulsory education less frequently than other analyzed diagnoses. There was a positive correlation between parental education levels and attendance in high school and university for both cases and controls. The risk of late complications after a brain tumor in childhood is high. Both the tumor itself and the treatments give rise to sequelae that affect daily life activities. In this registry study, we explored post-compulsory education, i.e., further education following the nine compulsory years in school, in 452 cases born 1988–1996 and diagnosed with a brain tumor before their fifteenth birthday. They were compared with 2188 individual controls who were not treated for cancer. Significantly fewer teenagers and young adults treated for brain tumors in childhood attended high school or university compared with controls, especially individuals treated for embryonal tumors or optic pathway gliomas. A significantly larger proportion of subjects treated for embryonal tumors and craniopharyngiomas attended folk high schools, a type of post-compulsory school with a more accessible learning environment. For both cases and controls, we observed a positive correlation between parental education levels and attendance in high school and university. In our previous studies we have shown that children treated for brain tumors, as a group, tend to perform worse during their last year of compulsory school compared with their peers, and the current study confirms that these differences remain over time. [ABSTRACT FROM AUTHOR]