<b><i>Introduction:</i></b> Neonatal hypoxic-ischemic brain injury (HIBI) results in significant morbidity and mortality despite current available therapies. Seeking a potential supplemental therapy for HIBI, we investigated the neuroprotective effects of extracellular vesicles derived from neural stem cells (NSC-EVs) and hypoxia-preconditioned brain cells (brain-EVs). <b><i>Methods:</i></b> HIBI was induced in postnatal day 9 mice by carotid ligation followed by hypoxia. Following injury, NSC-EVs, brain-EVs, or saline were administered intranasally. Brains were assessed for infarct size, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and caspase-3 expression. Additionally, brain-EV microRNA (miRNA) contents were analyzed by miRNA sequencing. <b><i>Results:</i></b> Both EV treated groups showed decreased infarct size (brain-EVs <i>p</i> = 0.004 and NSC-EVs <i>p</i> = 0.052), and although NSC-EV administration resulted in significantly fewer TUNEL+ cells (<i>p</i> = 0.0098), there was no change in caspase-3 expression after NSC-EV administration, suggesting a caspase-3-independent mechanism. Brain-EVs resulted in a nonsignificant decrease in TUNEL+ cells (<i>p</i> = 0.167) but significant decreases in caspase expression (cleaved <i>p</i> = 0.015 and intact <i>p</i> = 0.026). Brain-EVs consistently expressed several miRNAs, including two which have been shown to be downregulated after HIBI: miR-342-3p and miR-330-3p. <b><i>Conclusion:</i></b> Understanding the regenerative effects and contents of NSC-EVs and brain-EVs could allow for the development of targeted EV-based therapies that could reduce morbidity and mortality for neonates affected by HIBI.
SUMMARY This article describes a unique approach for reconstruction of large helical rim defects. By raising bilateral chondrocutaneous flaps of the helical rim while including a semicircular chondrocutaneous excision of the adjacent scapha and antihelix, large defects can be repaired with minimal loss to the overall external ear circumference. This is a technically simple and reliable method that has resulted in excellent cosmetic outcomes and minimal morbidity in our practice.
Migraine headache is a widespread and complex neurobiological disorder that is characterized by unilateral headaches that are often accompanied by photophobia and phonophobia. Migraine is one of the leading chief complaints in the emergency department with negative impacts on quality of life and activities of daily living. The high number of emergency presentations also results in a significant economic burden. Its risk factors include family history, genetics, sex, race, socioeconomics, the existence of comorbid conditions, and level of education. Triggers include stress, light, noise, menstruation, weather, changes in sleep pattern, hunger, dehydration, dietary factors, odors, and alcohol. The International Headache Society has defined criteria for the diagnosis of migraine with and without aura. The pathophysiology of migraine headaches is multifactorial so there are a variety of treatment approaches. The current treatment approach includes abortive medications and prophylactic medications. Abortive medications include the first-line treatment of triptans, followed by ergot alkaloids, and calcitonin gene-related peptide (CGRP) receptor antagonists along with supplemental caffeine and antiemetics. Trigeminal afferents from the trigeminal ganglion innervate most cranial tissues and many areas of the head and face. These trigeminal afferents express certain biomarkers such as calcitonin gene-related peptide (CGRP), substance P, neurokinin A, and pituitary adenylate cyclase-activating polypeptide that are important to the pain and sensory aspect of migraines. In this comprehensive review, we discuss Zavegepant, a calcitonin gene-related peptide receptor antagonist, as a new abortive medication for migraine headaches.
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