Overexpression of α-Klotho isoforms promotes distinct Effects on BDNF-Induced Alterations in Dendritic Morphology.

α-Klotho (α-Kl) is a modulator of aging, neuroprotection, and cognition. Transcription of the Klotho gene produces two splice variants-a membrane protein (mKl), which can be cleaved and released into the extracellular milieu, and a truncated secreted form (sKl). Despite mounting evidence supporting a role for α-Kl in brain function, the specific roles of α-Kl isoforms in neuronal development remain elusive. Here, we examined α-Kl protein levels in rat brain and observed region-specific expression in the adult that differs between isoforms. In the developing hippocampus, levels of isoforms decrease after the third postnatal week, marking the end of the critical period for development. We overexpressed α-Kl isoforms in primary cultures of rat cortical neurons and evaluated effects on brain-derived neurotrophic factor (BDNF) signaling. Overexpression of either isoform attenuated BDNF-mediated signaling and reduced intracellular Ca2+ levels, with mKl promoting a greater effect. mKl or sKl overexpression in hippocampal neurons resulted in a partially overlapping reduction in secondary dendrite branching. Moreover, mKl overexpression increased primary dendrite number. BDNF treatment of neurons overexpressing sKl resulted in a dendrite branching phenotype similar to control neurons. In neurons overexpressing mKl, BDNF treatment restored branching of secondary and higher order dendrites close, but not distal, to the soma. Taken together, the data presented support the idea that sKl and mKl play distinct roles in neuronal development, and specifically, in dendrite morphogenesis.

The Accreditation Council for Graduate Medical Education 20-Year Trends in Diversity, Equity, and Inclusion in the United States: How Does Neurological Surgery Compare?

BACKGROUND: Within the current medical workforce, diversity is limited among surgical specialties. However, diversity allows physicians to provide culturally competent care. This paper discusses the trends in racial, ethnic, and gender representation within different surgical subspecialties with an emphasis on neurosurgery over a 20-year time frame. METHODS: A retrospective review of data collected by the Accreditation Council for Graduate Medical Education over the past twenty years, as reported in Journal of the American Medical Association, was conducted. Residents from 5 surgical specialties were evaluated based on gender, race, and ethnic identifications from 2002 to 2022. One-way analysis of variance was performed to compare the levels and retention rates of racial, ethnic, and gender diversity within these specialties. RESULTS: Analysis of resident demographics of the 5 surgical specialties reveals an overall trend of increasing diversity over the study period. Over the past 20 years, neurosurgery had an overall increase in Asian (+5.1%), Hispanic (+3.0%), and female (+11.4%) residents, with a decrease in White residents by 2.1% and Black residents by 1.1%. Among the surgical specialties analyzed, otolaryngology had the greatest overall increase in minority residents. Notably, there has been an overall increase in female residents across all 5 surgical specialties, with the highest in otolaryngology (+20.3%) which was significantly more than neurosurgery (P < 0.001). CONCLUSIONS: This chronological analysis spanning 20 years demonstrates that neurosurgery, like other specialties, has seen a growth in several racial and ethnic categories. Relative differences are notable in neurosurgery, including Black, Asian, Hispanic, and White ethnic categories, with growth in females, but at a significantly lesser pace than seen in otolaryngology and plastic surgery.

Neurovascular considerations in patients with Down syndrome and moyamoya syndrome.

In this article, we describe a rare and complex case of moyamoya syndrome in a 7-year-old boy with Down syndrome and atlantoaxial subluxation. The patient presented with an ischemic stroke in the left hemisphere and cervical cord compression with increased cord edema. Diagnostic digital subtraction angiography revealed unique patterns of vascular involvement, with retrograde flow through the anterior spinal artery, ascending cervical artery, occipital artery, and multiple leptomeningeal arteries compensating for bilateral vertebral artery occlusion. This case underscores the underreported phenomenon of upward retrograde flow through the anterior spinal artery in bilateral vertebral artery occlusion. We address the rare manifestation of posterior circulation involvement in moyamoya syndrome, highlighting the importance of considering atlantoaxial instability as a contributing factor, as the absence of atlantoaxial stability is a risk factor for vertebral artery dissection. This study contributes valuable insights into the intricate relationship of moyamoya syndrome, Down syndrome, and atlantoaxial instability, urging clinicians to consider multifaceted approaches in diagnosis and treatment. It also emphasizes the potential significance of the anterior spinal artery as a compensatory pathway in complex vascular scenarios.