Role of the Dynorphin/KOR System in Mediating the Stress Response in Mice

Alcohol and drug abuse represent two of today’s greatest unsolved public health problems. The dynorphin/kappa opioid receptor (KOR) system has been shown to mediate the increased rewarding effects of drugs of abuse and the increased anxiety and stress seen during alcohol withdrawal. In the present study, we examined the role of the dynorphin/KOR system in the Bed Nucleus of the Stria Terminalis (BNST) in stress related behaviors using an animal model. We stereotaxically injected mice with an inducible caspase construct to selectively destroy dynorphin cells in the BNST and tested mice using the elevated plus maze (EPM), open field, and forced swim stress (FSS) behavioral paradigms. Our results show that under basal, non-stress conditions, ablating dynorphin from the BNST does not produce significant changes in behavior. However, dynorphin and KORs may play an important role in mediating behavior following a stressful event (FSS). Using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we show that functionally inhibiting dynorphin neurons in the BNST may have an anxiogenic effect under stressful conditions faced in the FSS-EPM behavioral paradigm. These results, along with an ongoing set of behavioral experiments with the DREADD mice, may provide novel insight for the role of the dynorphin/KOR system in mediating the stress response relevant to alcohol and drug use disorders.Bachelor of Scienc

Magnetic Hyperthermia Therapy for High-Grade Glioma: A State-of-the-Art Review

Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward

Prevalence of anemia and its relationship with neurological status in patients undergoing surgery for degenerative cervical myelopathy and radiculopathy: A retrospective study of 2 spine centers

Both degenerative cervical myelopathy (DCM) and anemia are common among older patients, however insufficient data exists evaluating their co-occurrence and the influence of anemia on baseline neurological status. To address this, we examined a retrospective multicenter series of patients treated for DCM or radiculopathy. Myelopathy was graded using the Nurick scale. Established criteria for diagnosing abnormalities were used to identify blood abnormalities, including macrocytic and microcytic anemia. Multivariable regression was used to determine the impact of hematological anomalies on Nurick grades. In our analysis, we included 725 patients (age of 57.1 ± 11.7), of whom 398 presented with myelopathy and 327 presented with radiculopathy alone. Twenty six percent of all patients were anemic at baseline and the mean preoperative Nurick grade across all patients was 2.09 ± 1.29; mean Nurick grade amongst those with DCM was 2.98 ± 1.12. Compared to those with myelopathy, patients with radiculopathy were significantly younger (53.8 ± 11.0 vs 59.8 ± 11.6, p < 0.001) and less likely to be anemic (16.8% vs 33.7%, p < 0.0001). Nurick grading was significantly higher in myelopathy patients with anemia (3.13 ± 1.19 vs 2.91 ± 1.07, p = 0.05) and macrocytic anemia (4.00 ± 1.41 vs 2.97 ± 1.11, p = 0.04). Multivariate regression demonstrated that anemia (p < 0.001), age (p < 0.0001), and posterior surgical approach (p < 0.0001) were related to worse preoperative Nurick grade. In sum, these data suggest that anemia and degenerative cervical spine pathologies commonly co-occur. Anemia, and macrocytic anemia specifically, is associated with poorer neurological status in myelopathic patients. These data suggest anemia may influence baseline neurological status and impact surgical recovery in patients treated for DCM or radiculopathy

Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺1-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺1-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺1-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19