Tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) is a signal transducer in the TNF receptor superfamily. TRAF7 is unique among its superfamily in that it does not contain a TRAF-C domain but does contain WD-40 domains. TRAF7 interacts with mitogen-activated protein kinases (MAPK), which are known regulators of inflammation and shear stress response. Notably, these molecular interactions have profound implications for the function of brain endothelial cells (ECs), which are pivotal for sustaining the integrity of the blood–brain barrier (BBB), orchestrating neurovascular coupling (NVC), and modulating the vascular architecture. By directly influencing MAPK signaling pathways, particularly the shear stress-responsive MAPK kinase kinase 3 (MEKK3)–MAPK kinase 5 (MEK5)–extracellular-regulated protein kinase 5 (ERK5) cascade, TRAF7 contributes to vascular homeostasis, as exemplified by its role in phosphorylating ERK5. Such molecular events underpin the capacity of brain ECs to regulate substance exchange, adjust blood flow in response to neural activity, and maintain efficient cerebral perfusion, all of which are essential for preserving brain health and cognitive performance. By synthesizing the current evidence regarding TRAF7’s molecular functions and its impact on brain endothelial integrity, cerebrovascular aging, and exploring implications for therapeutic strategies targeting vascular dysfunction in the aging brain, this review fills a crucial gap in the literature. Given the limited number of original studies directly addressing these contexts, the review will integrate broader insights from related literature to provide a foundational overview for future research in this developing field. The culmination of this literature will provide a rationale for the development of novel TRAF7-targeted therapies to restore vascular integrity in the context of aging, which could maintain cognitive health. Although TRAF7 has been implicated in regulating endothelial permeability during inflammation, its precise functions in brain ECs and the subsequent effects on cerebrovascular structure and cognitive function remain to be fully elucidated.
3 February 2019 in Journal of Neurological Surgery Part B: Skull Base
The presence of calcification is uncommon in pituitary adenomas, and often lends support to other diagnoses including craniopharyngioma. The majority of calcified pituitary adenomas are prolactin-secreting tumors. We report two patients with calcified macroprolactinomas, one that was treated medically with a biochemical response and partial tumor response, and one that was treated successfully via an endoscopic endonasal transsphenoidal approach. Suspected calcified prolactinomas can be initially managed medically as per standard treatment for typical prolactinomas; however, the presence of diffuse calcification may hinder tumor shrinkage. Tumors that are refractory to medical treatment can be safely managed with surgery.
BACKGROUND: Medical management is the first line of treatment for trigeminal neuralgia (TN). Patients with medically refractory TN may undergo a variety of invasive surgical interventions with varying success rates. Management of TN refractory to both medical and surgical intervention remains somewhat controversial. OBJECTIVE: To assess the effectiveness of Gamma Knife radiosurgery (GKRS; Elekta Instruments AB) for medically refractory TN. METHODS: A retrospective review was conducted for 57 cases (47 patients) who underwent GKRS for refractory TN at our institution between 2005 and 2018. TN pain outcomes were evaluated using the Barrow Neurological Institute (BNI) Pain Scale. A good outcome was defined by post-GKRS BNI score of I-III, whereas treatment failure was defined BNI score IV-V. RESULTS: Of the total 57 GKRS procedures, 47 (82.5%) had good outcomes. A total of 22 patients (46.8%) experienced complete pain relief off medications (BNI I). The average time to pain relief was 30 d (range 1-120 d). Prior invasive surgical treatment for TN was not found to have a significant impact on GKRS outcomes (P = .32). Target and treatment volumes were not found to correlate significantly with GKRS outcomes (.47 and .47, respectively). Complications included 2 cases (4.2%) of facial numbness. A total of 37 patients (78.7%) did not have any additional invasive surgical interventions following GKRS treatment. CONCLUSION: GKRS is a safe and effective treatment modality for both medically and surgically refractory TN. Complete symptom relief was possible in patients with prior surgical or GKRS treatments. Recurrent symptoms following surgery or GKRS should not exclude a patient from future GKRS consideration.