Background: Myostatin (MSTN) is a well-known negative regulator of skeletal muscle growth, and its pharmacological blockade, such as with follistatin (FST), an endogenous MSTN inhibitor, is under active investigation as a treatment for muscle-wasting conditions. However, the dynamics of MSTN signaling during in vitro myogenesis and its modulation by culture conditions remain incompletely understood. Methods: Primary myoblasts were isolated from wild-type (WT), Mstn-/-, and FST transgenic (F66) mice to evaluate the effects of MSTN inhibition on myotube formation. Myoblasts were differentiated on Matrigel-coated surfaces in the presence of horse serum. Myotube maturation was evaluated by confocal microscopy and reverse transcription-polymerase chain reaction; protein synthesis was assessed using a puromycin incorporation assay; and MSTN concentrations in serum were quantified by enzyme-linked immunosorbent assay. Results: Mstn expression peaked at 24 hr of differentiation, coinciding with early myotube formation, and progressively declined as myotubes matured. Both Mstn-/- and F66 myotubes showed increased thickness and protein synthesis compared to WT controls, with more pronounced effects observed in F66 myotubes. Consistent with this, F66 myotubes also displayed higher expression of myogenic maturation markers. Notably, horse serum used in the culture medium contained detectable levels of MSTN, which may have partially restored MSTN signaling in Mstn-/- cultures and masked the full knockout phenotype. Conclusions FST overexpression induces greater myotube hypertrophy and protein synthesis than Mstn deletion, likely due to its broader inhibition of both endogenous and serum-derived MSTN. These findings highlight the importance of serum composition in interpreting phenotypes from in vitro knockout models targeting secreted factors such as MSTN.

Basilar artery (BA) perforator aneurysms are exceedingly rare causes of subarachnoid hemorrhage. Therefore, the natural history and optimal treatment have not been established, and surgical, endovascular, and conservative management have been used. However, there is no consensus on the optimal treatment strategy. Herein, we report the case of a 52-year-old man presenting with a ruptured BA perforator aneurysm. First, we deployed an Enterprise stent from the left P1 segment to the BA because the microcatheter could not enter the aneurysm. Then, we deployed a helical coil on the orifice of the BA perforator. Finally, we deployed another Enterprise stent, sandwiching the helical coil between the two Enterprise stents. The aneurysm was completely obliterated without recurrence on the follow-up angiography. Our technique of sandwiching the small helical coil between two Enterprise stents might help other surgeons by offering another feasible treatment option for ruptured BA perforator aneurysms.

Myostatin, also known as growth differentiation factor 8 (GDF8), is a transforming growth factor-β (TGF-β) family member that functions to limit skeletal muscle growth. Accordingly, loss-of-function mutations in myostatin result in a dramatic increase in muscle mass in humans and various animals, while its overexpression leads to severe muscle atrophy. Myostatin also exerts a significant effect on bone metabolism, as demonstrated by enhanced bone mineral density and bone regeneration in myostatin null mice. The identification of myostatin as a negative regulator of muscle and bone mass has sparked an enormous interest in developing myostatin inhibitors as therapeutic agents for treating a variety of clinical conditions associated with musculoskeletal disorders. As a result, various myostatin-targeting strategies involving antibodies, myostatin propeptides, soluble receptors, and endogenous antagonists have been generated, and many of them have progressed to clinical trials. Importantly, most myostatin inhibitors also repress the activities of other closely related TGF-β family members including GDF11, activins, and bone morphogenetic proteins (BMPs), increasing the potential for unwanted side effects, such as vascular side effects through inhibition of BMP 9/10 and bone weakness induced by follistatin through antagonizing several TGF-β family members. Therefore, a careful distinction between targets that may enhance the efficacy of an agent and those that may cause adverse effects is required with the improvement of the target specificity. In this review, we discuss the current understanding of the endogenous function of myostatin, and provide an overview of clinical trial outcomes from different myostatin inhibitors.

BACKGROUND AND PURPOSE: The prevalence of unruptured cerebral aneurysms (UCAs) in ischemic stroke patients is not clearly defined. This study aimed to measure the prevalence and characteristics of UCAs in patients with acute ischemic stroke (AIS) and to compare our findings with those of the general population. In addition, we investigated the factors associated with cerebral aneurysms in AIS patients. METHODS: We retrospectively reviewed the brain magnetic resonance angiography images of 955 patients with AIS and 2,118 controls who had received a brain magnetic resonance angiography as part of a health check-up. We investigated the prevalence, size, location, and risk factors of the subjects in the context of UCAs. RESULTS: UCAs were found in 74 patients with AIS (7.7%) and in 79 who received a health check-up (3.7%). The prevalence of UCAs was significantly higher in the AIS group than in the health check-up group (odds ratio 2.17, 95% confidence interval 1.56-3.01). The mean aneurysm diameter was larger in the AIS group than in the health check-up group (3.75 mm vs. 3.02 mm, P=0.009). UCAs were primarily located in the internal carotid artery in both groups, and aneurysms in the middle cerebral artery were particularly common in the AIS group. According to multivariate analysis, hypertension alone was associated with an increased prevalence of UCAs in stroke patients. CONCLUSIONS: This study identified a higher prevalence and larger size of UCAs in AIS patients than in the general population. Hypertension was an independent risk factor of UCA in AIS.
Aneurysm ; Brachyura ; Brain ; Carotid Artery, Internal ; Humans ; Hypertension ; Intracranial Aneurysm* ; Magnetic Resonance Angiography ; Middle Cerebral Artery ; Multivariate Analysis ; Prevalence* ; Retrospective Studies ; Risk Factors ; Stroke*

PURPOSE: The operative risk and natural history rupture risk for the treatment of unruptured intracranial aneurysms (UIAs) should be evaluated. The purpose of this study was to report our experience with treating UIAs and to outline clinical risk factors associated with procedure-related major neurological complications. MATERIALS AND METHODS: We treated 1158 UIAs in 998 patients over the last 14 years. All patients underwent operation performed by a single microvascular surgeon and two interventionists at a single institution. Patient factors, aneurysm factors, and clinical outcomes were analyzed in relation to procedure-related complications. RESULTS: The total complication rate was 22 (2.2%) out of 998 patients. Among them, complications developed in 14 (2.3%) out of 612 patients who underwent microsurgery and in 8 (2.1%) out of 386 patients who underwent endovascular procedures. One patient died due to intraoperative rupture during an endovascular procedure. The procedure-related complication was highly correlated with age (p=0.004), hypertension (p=0.002), and history of ischemic stroke (p<0.001) in univariate analysis. The multivariate analysis revealed previous history of ischemic stroke (p=0.001) to be strongly correlated with procedure-related complications. CONCLUSION: A history of ischemic stroke was strongly correlated with procedure-related major neurological complications when treating UIAs. Accordingly, patients with UIAs who have a previous history of ischemic stroke might be at risk of procedure-related major neurological complications.
Aged ; Aneurysm, Ruptured ; Endovascular Procedures/*methods ; Female ; Humans ; Intracranial Aneurysm/epidemiology/*surgery ; Male ; Microsurgery ; Middle Aged ; Nervous System Diseases ; Neurosurgical Procedures ; Postoperative Complications/*epidemiology ; Risk ; Risk Assessment ; Risk Factors ; Treatment Outcome

OBJECTIVE: There are two established surgical treatment options for carotid artery stenosis. Carotid endarterectomy (CEA) has been accepted as a gold standard for surgical treatment while carotid artery stenting (CAS) has recently become an alternative option. Each treatment option has advantages and disadvantages for the treatment outcomes. We propose a protocol for selection of a proper surgical treatment option for carotid artery stenosis. MATERIALS AND METHODS: A total of 192 published articles on management of carotid artery stenosis were reviewed. Preoperatively considerable factors which had been repeatedly noted in those articles for the risk/benefits of CEA or CAS were selected. According to those factors, a protocol with four categories was established. RESULTS: CEA or CAS is indicated when the patient has a symptomatic stenosis > or = 50%, or when the patient has an asymptomatic stenosis > or = 80%. Each treatment option has absolute indications and favorable indications. Each absolute indication is scored with three points, and each favorable indication, one point. Based on the highest scores, a proper treatment option (CEA or CAS) is selected. CONCLUSION: We have been treating patients according to this protocol and evaluating the outcomes of our protocol-based decision because this protocol might be helpful in assessment of risk/benefit for selection of a proper surgical treatment option in patients with carotid artery stenosis.
Carotid Arteries ; Carotid Stenosis* ; Constriction, Pathologic ; Endarterectomy, Carotid ; Humans ; Stents