Coenzyme Q10 inhibits intracranial aneurysm formation and progression in a mouse model.

BACKGROUND: The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10), a commonly used nutritional supplement, on intracranial aneurysm (IA) initiation and progression in a mouse model, as well as the mechanism. METHODS: Hydrogen peroxide (H2O2) was used to treat mouse-derived vascular smooth muscle cells (VSMCs) to induce oxidative injury, followed by incubation with CoQ10. In the mouse IA model established by elastase injection, CoQ10 was orally administered at 10 mg/kg every other day for 14 days, during which the incidence of IA, rupture rate, symptom-free survival, and systolic blood pressure were recorded. RESULTS: CoQ10 promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes. In H2O2-treated VSMCs, reactive oxygen species and cell apoptosis were reduced by CoQ10. In IA mice, CoQ10 treatment decreased the rupture rate of IA, improved the symptom-free survival, and reduced systolic blood pressure. Macrophage infiltration and expression of pro-inflammatory cytokines in the cerebral arteries were mitigated by CoQ10 treatment. CONCLUSIONS: CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice. CoQ10 also alleviates inflammation and restores normal phenotypes of VSMCs in the cerebral arteries. Our data suggest that CoQ10 is a potentially effective drug for managing IA. IMPACT: To investigate the effect of CoQ10, a commonly used nutritional supplement, on IA initiation and progression in a mouse model, as well as the mechanism. CoQ10 promoted the expression of Nrf2 and antioxidant enzymes. In H2O2-treated VSMCs, ROS and cell apoptosis were reduced by CoQ10. CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice.

Multiple overlapping stent-assisted coiling improves efficacy and safety of treatment for complex intracranial aneurysms: a randomized trial.

BACKGROUND: Intracranial aneurysm rupture is the main cause of subarachnoid hemorrhage, leading to high disability and mortality. This study aimed to evaluate the clinical treatment effects of multiple overlapping stent-assisted coiling for complex intracranial aneurysms. METHODS: We conducted a randomized, controlled, single-blinded clinical trial among 168 patients diagnosed with complex intracranial aneurysms. Treatment allocation to either single stent (SS) group or multiple stent (MS) group was randomized at 1:1 ratio using a Web-based platform. The O'Kelly-Marotta (OKM) grading scale was used to evaluate the degree of aneurysm occlusion after operation and during follow-up. Good aneurysm occlusion was defined as OKM grade C-D. The modified Rankin Scale (mRS) was used to evaluate the neurological status and the clinical outcome of patients. RESULTS: Efficacy comparative analysis demonstrated that major recurrence of aneurysms was significantly reduced in the MS group (P = 0.012). In addition, the MS group displayed significantly reduced number of patients with mRS between 3 and 6 (P = 0.007) and increased number of patients with mRS between 0 and 1 (P = 0.034). Furthermore, the MS group showed increased percentage of patients with OKM grade C-D (P = 0.041). Compared with the SS group, the MS group exhibited decreased mortality (P = 0.037) and morbidity (P = 0.035). CONCLUSIONS: Multiple overlapping stent-assisted coiling significantly improved the clinical treatment effects and provided a new method for complex intracranial aneurysms.

Protective effects of BP-1-102 against intracranial aneurysms-induced impairments in mice.

The development of non-invasive pharmacological therapies to prevent the progression and rupture of intracranial aneurysms (IAs) is an important field of research. This study attempts to reveal the role of BP-1-102, an oral bioavailable signal transducer and activator of transcription 3 (STAT3) inhibitor, in IA. We first constructed an IA mouse model by injecting elastase into the cerebrospinal fluid with simultaneous induction of hypertension by deoxycorticosterone acetate (DOCA) implantation. The results showed that the proportion of IA rupture in mice after BP-1-102 administration was significantly reduced, and the survival time was significantly extended. Further research showed that compared with the vehicle group, the proportion of macrophages infiltrated at the aneurysm and the expression of pro-inflammatory cytokines in the BP-1-102 administration group were significantly reduced. The contractile phenotype vascular smooth muscle cell (VSMC) specific markers, SM22α and αSMA, were significantly upregulated in the BP-1-102 group. Furthermore, we found that BP-1-102 inhibited the expression of critical proteins in the nuclear factor kappa-B and Janus kinase 2/STAT3 signalling pathways. Our study shows that BP-1-102 significantly decreases the rupture of IA, reduces the inflammatory responses and modulates the phenotype of VSMCs, suggesting that BP-1-102 could be utilised as a potential intervention drug for IA.

Pharmacological inhibition of STAT3 by BP-1-102 inhibits intracranial aneurysm formation and rupture in mice through modulating inflammatory response.

As an inhibitor of STAT3, BP-1-102 can regulate the inflammation response caused by vascular smooth muscle cells (VSMCs) by inhibiting the JAK/STAT3/NF-κB pathway, thereby attenuating the symptoms of intracranial aneurysm (IA). IA mouse model was established by stereotactic injection of elastase to evaluate the effect of BP-1-102. The expression levels of smooth muscle markers and matrix metalloproteinases (MMPs) were detected by qRT-PCR, and the levels of inflammatory factors were detected by ELISA and qRT-PCR. The protein levels of the NF-κB signaling pathway factors were examined by Western blot. BP-1-102 reduced blood pressure in aneurysm mice, up-regulated smooth muscle cell markers MHC, SMA, and SM22, and down-regulated the expression of MMP2 and MMP9 in vascular tissues. At the same time, BP-1-102 also down-regulated the expression levels of inflammatory response factors and the NF-κB pathway proteins. In the IA model, BP-1-102 can reduce the expression of inflammatory factors and MMPs bound to NF-κB by inhibiting the activation of the JAK/STAT3/NF-κB pathway proteins, and then restore the vascular wall elastin to reduce blood pressure, thereby treating aneurysm.

STAT3 Contributes to Intracranial Aneurysm Formation and Rupture by Modulating Inflammatory Response.

Intracranial aneurysm (IA) is a common type of refractory cerebrovascular diseases. Inflammatory responses have been reported to be associated with the pathogenesis of IA. We aimed to study the role of STAT3 on IA formation and inflammatory response. STAT3 expression and clinicopathological factors were analyzed in IA and normal cerebral arteries. mRNA level of STAT3 was detected in normal, unruptured, and ruptured IA tissues by RT-PCR and Western blot. Inflammatory cytokines were examined by ELISA in unruptured, ruptured IA tissues, as well as cells with STAT3 overexpression or knockdown. mRNA of phenotypic modulation-related factors was tested by RT-PCR in STAT3 overexpressing or knockdown VSMCs. STAT3 expression was upregulated in ruptured IA tissues and highly associated with IA diameter and IA type. Inflammatory cytokine secretion was increased in ruptured IA samples and positively correlated with STAT3 expression. STAT3 overexpression led to enhanced expression of SM-α actin, SM-MHC, MMP2, and MMP9, and increased secretion of inflammatory cytokines. Our findings have demonstrated that STAT3 is a key regulator in IA formation by modulating inflammatory cytokine expression.

Catechin attenuates traumatic brain injury-induced blood-brain barrier damage and improves longer-term neurological outcomes in rats.

NEW FINDINGS: What is the central question of this study? We investigated the potential neuroprotective effects of catechin after traumatic brain injury and explored the underlying mechanisms. What is the main finding and its importance? Catechin treatment had neuroprotective effects in a rat model of traumatic brain injury, and these effects might be mediated by intervention in the self-perpetuating process of blood-brain barrier disruption and excessive inflammatory reaction. Traumatic brain injury (TBI) resulting from external force on the head usually leads to long-term deficits in motor and cognitive functions. Catechin has shown neuroprotective effects in neurodegenerative diseases and ischaemia models. We therefore investigated the potential neuroprotective effects of catechin after TBI and explored the underlying mechanisms. Male rats were subjected to controlled cortical impact injury and then treated with catechin. Brain damage, motor and cognitive functions, blood-brain barrier (BBB) integrity and neuro-inflammation were examined. Catechin treatment ameliorated brain damage and motor and cognitive deficits after TBI. Catechin was shown to protect BBB integrity, alleviate the TBI-induced loss of the junction proteins occludin and zonula occludens protein-1 and suppress local inflammatory reactions. Catechin treatment had neuroprotective effects in a rat model of TBI, and these effects might be mediated by intervention in the self-perpetuating process of BBB disruption and excessive inflammatory reaction.

Intraoperative electrocorticography-guided microsurgical management for patients with onset of supratentorial neoplasms manifesting as epilepsy: a review of 65 cases.

AIM: We reviewed the surgical procedures guided by intraoperative electrocorticography and outcome of 65 patients with onset of supratentorial neoplasms manifesting as epilepsy. METHOD: Clinical data were obtained for 65 patients with supratentorial neoplasms who received surgery, with the aid of intraoperative electrocorticography to screen epileptogenic foci before and after removal of neoplasms, and depth electrodes when needed. According to electrocorticography findings, appropriate surgical procedures were performed to treat the epileptogenic foci. In the control group, 72 patients received simple lesionectomy. Postoperative seizure outcomes were documented and analysed retrospectively. RESULTS: In the case group, 33 patients received lesionectomy only, while the other 32 patients underwent intraoperative electrocorticography-guided tailored epilepsy surgery. In total, 57 patients (87.7%) in the case group and 38 patients (52.8%) in the control group were seizure-free (Engel Class I). Comparing outcomes of patients with temporal lesions between the two groups, 80.0% patients (12/15) in the case group and 20.0% (3/15) in the control group were seizure-free. Furthermore, comparing the seizure outcomes of patients who finally underwent tailored epilepsy surgery and simple lesionectomy (33 after electrocorticography and 72 without electrocorticography), intraoperative electrocorticography-guided tailored epilepsy surgery demonstrated superiority over lesionectomy (Engel Class I; 87.5% vs. 63.8%, respectively). CONCLUSIONS: Electrocorticography plays an important role in the localisation of epileptogenic foci and evaluation of the effects of microsurgical procedures intraoperatively. Isolated lesionectomy is not usually sufficient for better postoperative seizure outcome. In addition, for patients with temporal tumours, especially in the non-dominant hemisphere, a more aggressive strategy, such as an anterior temporal lobectomy, is recommended.