Molecular and histological correlates of cognitive decline across age in male C57BL/6J mice.

INTRODUCTION: Increasing age is the number one risk factor for developing cognitive decline and neurodegenerative disease. Aged humans and mice exhibit numerous molecular changes that contribute to a decline in cognitive function and increased risk of developing age-associated diseases. Here, we characterize multiple age-associated changes in male C57BL/6J mice to understand the translational utility of mouse aging. METHODS: Male C57BL/6J mice from various ages between 2 and 24 months of age were used to assess behavioral, as well as, histological and molecular changes across three modalities: neuronal, microgliosis/neuroinflammation, and the neurovascular unit (NVU). Additionally, a cohort of 4- and 22-month-old mice was used to assess blood-brain barrier (BBB) breakdown. Mice in this cohort were treated with a high, acute dose of lipopolysaccharide (LPS, 10 mg/kg) or saline control 6 h prior to sacrifice followed by tail vein injection of 0.4 kDa sodium fluorescein (100 mg/kg) 2 h later. RESULTS: Aged mice showed a decline in cognitive and motor abilities alongside decreased neurogenesis, proliferation, and synapse density. Further, neuroinflammation and circulating proinflammatory cytokines were increased in aged mice. Additionally, we found changes at the BBB, including increased T cell infiltration in multiple brain regions and an exacerbation in BBB leakiness following chemical insult with age. There were also a number of readouts that were unchanged with age and have limited utility as markers of aging in male C57BL/6J mice. CONCLUSIONS: Here we propose that these changes may be used as molecular and histological readouts that correspond to aging-related behavioral decline. These comprehensive findings, in the context of the published literature, are an important resource toward deepening our understanding of normal aging and provide an important tool for studying aging in mice.

Cholesterol granulomas presenting as sellar masses: a similar, but clinically distinct entity from craniopharyngioma and Rathke's cleft cyst.

PURPOSE: Cholesterol granulomas in the sella are rare and can mimic the appearance of craniopharyngioma or Rathke's cleft cysts. Information regarding the clinical presentation, imaging characteristics, and clinical course of sellar cholesterol granulomas can help clinicians to differentiate these lesions from other sellar cystic lesions. METHODS: We present three cases of sellar cholesterol granulomas. A literature review was performed for all cases of sellar cholesterol granulomas with individual patient data reported. RESULTS: We identified 24 previously reported cases in addition to our three cases. Mean age was 36.6 years (range 5-68). There were 16 (59%) females. The most common (74%) presenting symptom was endocrinological deficits, typically either isolated diabetes insipidus (DI) or panhypopituitarism. Location was intrasellar in 3 (11%), suprasellar in 6 (22%), and intrasellar/suprasellar in 18 (67%) patients. Lesions were most commonly (83%) T1 hyperintense. Gross total resection was achieved in 16 (64%) and subtotal resection in 9 (36%) patients. Of the seventeen (63%) patients presenting with varying degrees of bitemporal hemianopsia, all had improvement in vision postoperatively. It is worth noting that no cases of preoperative hypopituitarism or DI improved postoperatively. Even though gross total resection was only achieved in 64%, there was only one recurrence reported. CONCLUSION: Sellar cholesterol granulomas are characterized by T1 hyperintensity, younger age, and more frequent and severe endocrinological deficits on presentation. Our review demonstrates high rates of improvement of visual deficits, but poor rates of endocrine function recovery. Recurrence is uncommon even in cases of subtotal resection.