Cell Transplantation for Repair of the Spinal Cord and Prospects for Generating Region-Specific Exogenic Neuronal Cells.

Spinal cord injury (SCI) is associated with currently irreversible consequences in several functional components of the central nervous system. Despite the severity of injury, there remains no approved treatment to restore function. However, with a growing number of preclinical studies and clinical trials, cell transplantation has gained significant potential as a treatment for SCI. Researchers have identified several cell types as potential candidates for transplantation. To optimize successful functional outcomes after transplantation, one key factor concerns generating neuronal cells with regional and subtype specificity, thus calling on the developmental transcriptome patterning of spinal cord cells. A potential source of spinal cord cells for transplantation is the generation of exogenic neuronal progenitor cells via the emerging technologies of gene editing and blastocyst complementation. This review highlights the use of cell transplantation to treat SCI in the context of relevant developmental gene expression patterns useful for producing regionally specific exogenic spinal cells via in vitro differentiation and blastocyst complementation.

Sensitivity to the initial rewarding effects of alcohol: Influence of age, sex, and ß-endorphin.

BACKGROUND: Alcohol use disorders (AUDs) are widespread, devastating and complex. About 20% of people who consume alcohol develop problem use, accounting for over 5% of worldwide deaths. While numerous animal models have facilitated understanding of the consequences of excessive drinking, translational models allow for experimental manipulation of factors thought to contribute to AUD liability. METHODS: We employ a single-exposure conditioned place preference assay (SE-CPP) to investigate the influence of age, sex and the opioid peptide ß-endorphin (bE) on the initial rewarding effects of ethanol, a strong predictor of AUDs. Adolescent (PND28-35) and adult (PND70-90) male and female, control C57BL/6J and bE-deficient mice were tested following a single injection of 1.5 g/kg of ethanol. Following the SE-CPP test, animals were deeply anesthetized, sacrificed, and perfused, and the brains were subsequently sectioned at 40 microns and processed for immunohistochemical localization of c-fos. One-sample, two-tailed t-tests were used to assess drug preference or aversion and the locomotor effects of alcohol. RESULTS: In general, adults were more sensitive to the effects of alcohol than adolescents, and outcomes depended on sex and bE. For example, among females, adolescents were stimulated by the drug, but insensitive to locomotor effects as adults, while among males, adolescents were insensitive and adults sedated. Wild-type adolescents of both sexes failed to evince initial subjective reward from the drug, but bE-deficient adolescents, and all adult subjects, preferred a context once associated with ethanol over one that had been paired with saline. c-fos immunoreactivity in multiple brain regions was attenuated in bE-deficient animals, though influences of both sex and bE grew stronger with age. CONCLUSIONS: This study demonstrates the utility of the SE-CPP paradigm for elucidating factors that contribute to the liability for AUDs, and supports the growing body of research that shows that sensitivity to the rewarding effects of alcohol changes during the course of development. Our results also suggest that developmental contributions are sex-dependent, and may also depend on the influence of endogenous opioid signaling.

Stage IV Neuroblastoma with Metastatic Spread to the Mandible in a Young Child: Case Report and Review of the Literature.

BACKGROUND: Infants and young children with neuroblastoma (NB) may present with metastases. The primary tumor most commonly originates in the abdomen and metastasizes to lymph nodes, liver, and bone marrow. Infants and young children presenting with multiple skull metastases are rare. METHODS: We present a rare case of a 20-month-old child who presented with metastatic neuroblastoma and multiple skull lesions. The child responded well to induction chemotherapy followed by myeloablative busulfan/melphalan consolidation. RESULTS: The child had substantial tumor reduction after chemotherapy was started. There was a significant decrease in tumor sizes and uptake, as seen in the metaiodobenzylguanidine study. The 6-month follow-up examination showed complete remission, and the remission continues. CONCLUSIONS: Infants and young children with neuroblastoma rarely present with metastatic lesions to the skull. Even large lesions involving the skull base may be successfully treated with chemotherapy. The use of myeloablative busulfan/melphalan consolidation after induction chemotherapy can decrease the overall metastatic tumor burden. Craniofacial specialists should be aware of treatment options for these young children.