Stroke is a devastating neurological disorder and a leading cause of death and long-term disability. Despite many decades of research, there are still very few therapeutic options for patients suffering from stroke or its consequences. This is partially due to the limitations of current research models, including traditional in vitro models which lack the three-dimensional (3D) architecture and cellular make-up of the in vivo brain. 3D spheroids derived from primary postnatal rat cortex provide an in vivo-relevant model containing a similar cellular composition to the native cortex and a cell-synthesized extracellular matrix. These spheroids are cost-effective, highly reproducible, and can be produced in a high-throughput manner, making this model an ideal candidate for screening potential therapeutics. To study the cellular and molecular mechanisms of stroke in this model, spheroids were deprived of glucose, oxygen, or both oxygen and glucose for 24 hours. Both oxygen and oxygen-glucose deprived spheroids demonstrated many of the hallmarks of stroke, including a decrease in metabolism, an increase in neural dysfunction, and an increase in reactive astrocytes. Pretreatment of spheroids with the antioxidant agent N-acetylcysteine (NAC) mitigated the decrease in ATP seen after 24 hours of oxygen-glucose deprivation. Together, these results show the utility of our 3D cortical spheroid model for studying ischemic injury and its potential for screening stroke therapeutics.
OBJECTIVE US allopathic medical schools have experienced improvements in racial and ethnic diversity among matriculants in the past decade. It is not clear, however, whether better representation of historically excluded racial and ethnic groups at medical school entry impacts subsequent stages of the medical training pipeline leading into a specific field. The aim of this study was to examine these trends as they relate to the neurosurgical medical education pipeline and consider the drivers that sustain barriers for underrepresented groups. METHODS Race and ethnicity reports from the American Association of Medical Colleges were obtained on allopathic medical school applicants, acceptees, and graduates and applicants to US neurosurgical residency programs from 2012 to 2020. The representation of groups categorized by self-reported race and ethnicity was compared with their US population counterparts to determine the representation quotient (RQ) for each group. Annual racial composition differences and changes in representation over time at each stage of medical training were evaluated by estimating incidence rate ratios (IRRs) and 95% confidence intervals (CIs) using non-Hispanic Whites as the reference group. RESULTS On average, Asian and White individuals most frequently applied and were accepted to medical school, had the highest graduation rates, and applied to neurosurgery residency programs more often than other racial groups. The medical school application and acceptance rates for Black individuals increased from 2012 to 2020 relative to Whites by 30% (95% CI 1.23–1.36) and 42% (95% CI 1.31–1.53), respectively. During this same period, however, inequities in neurosurgical residency applications grew across all non-Asian racialized groups relative to Whites. While the incidence of active Black neurosurgery residents increased from 2012 to 2020 (0.6 to 0.7/100,000 Black US inhabitants), the prevalence of White neurosurgery residents grew in the active neurosurgery resident population by 16% more. CONCLUSIONS The increased racial diversity of medical school students in recent years is not yet reflected in racial representation among neurosurgery applicants. Disproportionately fewer Black relative to White US medical students apply to neurosurgery residency, which contributes to declining racial representation among all active neurosurgery resident physicians. Hispanic individuals are becoming increasingly represented in neurosurgery residency but continue to remain underrepresented relative to the US population. Ongoing efforts to recruit medical students into neurosurgery who more accurately reflect the diversity of the general US population are necessary to ensure equitable patient care.
Purpose Ischemic brain injury occurs when there is reduced or complete disruption of blood flow to a brain region, such as in stroke or severe traumatic brain injury. Even short interruptions can lead to devastating effects including excitotoxicity and widespread cell death. Despite many decades of research, there are still very few therapeutic options for patients suffering from brain ischemia. Methods We developed an in vitro brain ischemia model using our previously established 3D spheroids derived from primary postnatal rat cortex. These spheroids provide an in vivo-relevant model containing a similar cellular composition to the native cortex and a cell-synthesized extracellular matrix. This model is cost-effective, highly reproducible, and can be produced in a high-throughput manner, making it an ideal candidate for screening potential therapeutics. To study the cellular and molecular mechanisms of stroke in this model, spheroids were deprived of glucose, oxygen, or both oxygen and glucose for 24 h. Results Both oxygen and oxygen-glucose deprived spheroids demonstrated many of the hallmarks of ischemic brain injury, including a decrease in metabolism, an increase in neural dysfunction, breakdown in the neurovascular unit, and an increase in reactive astrocytes. Pretreatment of spheroids with the antioxidant agent N-acetylcysteine (NAC) mitigated the decrease in ATP after oxygen-glucose deprivation, was partially neuroprotective, and enhanced the expression of laminin. Conclusion This 3D cortical spheroid model provides a platform for studying ischemic injury and has the potential for screening therapeutics. Keywords 3D in vitro models • Brain ischemia • Screening • Central nervous system
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