ABSTRACT
BACKGROUND: The brain extracellular environment is involved in many critical processes associated with neurodevelopment, neural function, and repair following injury. Organization of the extracellular matrix and properties of the extracellular space vary throughout development and across different brain regions, motivating the need for platforms that provide access to multiple brain regions at different stages of development. We demonstrate the utility of organotypic whole hemisphere brain slices as a platform to probe regional and developmental changes in the brain extracellular environment. We also leverage whole hemisphere brain slices to characterize the impact of cerebral ischemia on different regions of brain tissue. RESULTS: Whole hemisphere brain slices taken from postnatal (P) day 10 and P17 rats retained viable, metabolically active cells through 14 days in vitro (DIV). Oxygen-glucose-deprivation (OGD), used to model a cerebral ischemic event in vivo, resulted in reduced slice metabolic activity and elevated cell death, regardless of slice age. Slices from P10 and P17 brains showed an oligodendrocyte and microglia-driven proliferative response after OGD exposure, higher than the proliferative response seen in DIV-matched normal control slices. Multiple particle tracking in oxygen-glucose-deprived brain slices revealed that oxygen-glucose-deprivation impacts the extracellular environment of brain tissue differently depending on brain age and brain region. In most instances, the extracellular space was most difficult to navigate immediately following insult, then gradually provided less hindrance to extracellular nanoparticle diffusion as time progressed. However, changes in diffusion were not universal across all brain regions and ages. CONCLUSIONS: We demonstrate whole hemisphere brain slices from P10 and P17 rats can be cultured up to two weeks in vitro. These brain slices provide a viable platform for studying both normal physiological processes and injury associated mechanisms with control over brain age and region. Ex vivo OGD impacted cortical and striatal brain tissue differently, aligning with preexisting data generated in in vivo models. These data motivate the need to account for both brain region and age when investigating mechanisms of injury and designing potential therapies for cerebral ischemia.
ABSTRACT
Primary hyperparathyroidism (PHPT) predominantly affects older adults, and parathyroidectomy can achieve definitive cure in symptomatic PHPT and asymptomatic meeting surgical criteria. As the population continues to age, the treatment of PHPT in octogenarians and nonagenarians presents a clinical conundrum. This case series presents the management of eight patients 85 years of age and older diagnosed with PHPT. A retrospective chart review of patients diagnosed with primary hyperparathyroidism were identified in a single institution. Those patients 85 years of age and older who were followed up for over one year were included in this case series. The literature on treatment options for this age group was also reviewed. Eight cases of PHPT patients aged 88 ± 2.5 years old with a follow-up average of 5.6 ± 4.4 years were reported in our case series. Six PHPT patients were medically managed and two PHPT patients underwent parathyroid resection. Most of the medically managed PHPT patients except for one had long-term stability of disease for over five years. The treatment of PHPT diagnosed in patients over 85 years of age presents a clinical challenge for which there is no clear consensus guideline. Our case series supports that medical therapy is a feasible option for PHPT patients over 85 years old.
