Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders.

In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.

Aim: Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies for the treatment of functionally compromised tissue beds and organ sites. Here we aimed to highlight multiple administration routes for the potential treatment of various forms of brain injury. Methods: Human neural stem cell-derived EV were isolated from conditioned media and administered via three distinct routes: intrahippocampal transplantation, retro-orbital vein injection, and intranasal. EV were administered after which brains were evaluated to determine the capability of EV to translocate into normal tissue. Results: Data showed no significant differences in the amount of EV able to translocate across the brain, indicating the functional equivalence of each administration route to effectively deliver EV to the brain parenchyma. Conclusion: Findings show that both systemic administration routes (retro-orbital vein or intranasal delivery) afforded effective penetrance and perfusion of EV throughout the brain in a minimally invasive manner, and point to a translationally tractable option for treating certain neurological disorders including those resulting from cranial irradiation procedures.

Purpose: To evaluate outcomes of proton therapy and x-ray radiation treatments for head and neck paragangliomas. Patients and Methods: Between 2004 and 2014, 13 patients with paragangliomas were treated with radiation using proton therapy (n ¼ 7) or x-ray modalities (n ¼ 6). Paragangliomas were jugular fossa, vagal, tympanic, and carotid body in 5, 4, 2, and 2 patients, respectively. Patients were treated definitively (n ¼ 8), for recurrence or progression after prior surgery (n ¼ 4), or for residual tumor after surgery (n ¼ 1). The median age was 55 years (range, 35 to 77 years). The median dose of proton therapy was 35 Gy (RBE) in 15 fractions, and 50.4 Gy in 28 fractions for those treated with xrays. Tumor volume was delineated at treatment planning and on follow-up images to assess volumetric changes over time. The median follow-up time after proton therapy was 52 months (range, 6 to 105 months) and 73 months (range, 37 to 91 months) after xray therapy. Results: No acute grade 3 or greater toxicities occurred. After radiation therapy, tumor control was maintained and performance status was unchanged or improved in all patients. Of the patients, 10 had stable findings, 2 had improvement in preexisting cranial nerve deficits, and 1 had progression of previously intermittent vocal cord paresis to paralysis, compensated by vocal-fold injection. No secondary malignancies have been observed. Volumetric tumor response assessment found 1 patient with an increase in tumor volume of 0.4 cm 3 at first postradiation assessment, followed by 6 years of stable tumor size. The remaining 12 patients had reduction in tumor volume over time with a median tumor volume reduction of 33% at the last follow-up. The median tumor regression slope for the proton cohort was À1.21 cm 3 /y compared with À0.27 cm 3 /y in the x-ray cohort (P ¼ .02). Conclusion: Both proton and x-ray radiation were effective in treating paraganglioma and had minimal acute side effects and few long-term complications.

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