FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

Comparison of Aggressive Surgical Treatment and Palliative Treatment in Elderly Patients with Poor-Grade Intracranial Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To compare the current treatment approach in elderly patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) and identify the independent predictors of the outcome after aggressive surgical treatment. METHOD: This prospective, multicenter cohort study included 104 poor-grade aneurysmal SAH elderly patients, 60 years or older, treated in our institution from October 2010 to March 2013. Patients were grouped according to three treatment arms. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at baseline and at a 12-month follow-up. Univariate and multivariate analysis were performed using the following factors: sex, age, smoking history, breathing ability, alcohol consumption, cerebral hernia, aneurysm location, aneurysm diameter, WFNS grade, CT Fisher grade, treatment approach, and the timing of the aneurysm surgery. RESULTS: At the 12-month follow-up, patients in the coiling group and clipping group had better prognosis than patients in the palliative treatment group. Univariate analysis confirmed that the treatment approach, WFNS grade, CT Fisher grade, and age are critical factors for neurological outcomes in poor-grade SAH. Multivariate analysis indicated that WFNS grade V, CT Fisher grades 3-5, and palliative treatment were independent predictors of poor prognoses. CONCLUSION: Aggressive surgical treatment improves the prognoses in poor-grade aneurysm elderly patients with SAH. Elderly Patients of WFNS grade IV and CT Fisher grades 1-2 are more likely to have a better outcome.

[Analysis of prognostic factors on posterior communicating artery aneurysm caused oculomotor nerve palsy].

OBJECTIVE: To study and analyze the factors affecting the recovery of posterior communicating artery aneurysm-induced oculomotor nerve palsy (ONP). METHODS: The clinical and follow-up data of posterior communicating artery aneurysm-induced ONP in 23 patients from May 2005 to May 2009 were retrospectively compared. There were 7 male and 16 female with a mean age of 50.4 years. Among the 23 patients, 13 patients underwent endovascular coiling (endovascular group) and 10 patients underwent surgical clipping (surgical group). RESULTS: Of the patients with 2 year of follow-up, 6 patients recovered completely and 7 patients recovered partially in the endovascular group, compared with 6 patients recovered completely and 4 patients recovered partially in the surgical group (P = 0.407). Compared to the patients with preoperative complete ONP, the rate of complete recovery was higher in the patients with preoperative partial ONP, while the results did not reach the significance (P = 0.095). Patients accepted treatment in 14 days since the onset of symptoms recovered significantly than who accepted treatment after 14 days since the onset of symptoms (P = 0.045). CONCLUSIONS: There is no significant difference in recovery from ONP between endovascular coiling and surgical clipping as treatment for posterior communicating artery aneurysm patients with ONP. Timing of treatment after onset of symptoms is a factor affects the recovery of ONP.

Computed tomography angiography based emergency microsurgery for massive intracranial hematoma arising from arteriovenous malformations.

BACKGROUND: Digital subtraction angiography (DSA) and magnetic resonance angiography are the imaging modalities for the detection of intracranial arteriovenous malformations. However, these modalities are time consuming and cannot be used in emergency conditions. Computed tomography angiography (CTA) has also been shown to reliably detect vascular disorders such as cerebral arteriovenous malformations (AVMs). AIMS: The purpose of this study was to evaluate the usefulness CTA in the surgical treatment of AVMs and the hematoma evacuation. PATIENTS AND METHODS: Case records of 18 patients with massive intracranial hematoma secondary to AVMs were retrospectively reviewed. All patients had emergent brain CT and CTA. Follow-up DSA was performed two to three weeks after surgery. The outcome was assessed using Glasgow Outcome Scale (GOS). Results : Emergent CTA demonstrated AVMs and defined the feeding arteries, abnormal vascular nest, and draining veins in all the patients. Fourteen patients underwent hematoma evacuation and total resection of the AVMs, and four patients had hematoma evacuation and a partial resection. Follow-up DSA demonstrated complete resection of AVM in 14/18 patients and partial resection in 4 patients. There were no deaths and none of the patients had rebleeding in the follow up. A GOS scores during follow-up were: GOS 3 in 12 patients, GOS 4 in 4 patients and GOS 2 in 2 patients. CONCLUSIONS: CTA can be a reliable and rapid diagnostic tool for detecting underlying AVM in patients presenting with intracranial hematoma and for the pretreatment planning of emergency craniotomy.

Diagnostic value of CTA and MRA in intracranial traumatic aneurysms.

OBJECTIVE: To investigate the diagnostic value of computerized tomographic angiography (CTA) and magnetic resonance angiography (MRA) for intracranial traumatic aneurysms (TAs). METHODS: CTA and MRA of six patients with intracranial TAs verified by digital subtraction angiography (DSA) and surgery were retrospectively analysed. All patients were examined by nonenhanced computerized tomography (CT) and two by CTA. The source data were reconstructed by volume rendering (VR) and multi-planar reconstruction (MPR) from CTA. Four of them had maximum intensity project (MIP) from MRA. RESULTS: Of the six patients, a total of seven TAs were detected by CTA and MRA examinations. Five cases had only one TA and one case had two TAs. The average diameter was 2.3 cm (1.1-3.3 cm). CTA demonstrated two TAs appeared at the cavernous segment of the internal carotid artery (ICA) and the middle cerebral artery (MCA) respectively. MCA TA was definitely and clearly demonstrated on VR images, whereas VR images failed to depict the cavernous ICA TA, which was detected on MPR images. Two TAs were found irregular saccular shape, irregular margin of parent artery and wide neck on CTA. Four MRA examinations demonstrated five TAs, including the cavernous segment ICA TAs (2 cases), the supraclinoid segment ICA TA (1 case), and the cavernous segment associated with opposite side of the petrosal segment ICA TA (1 case). In a cavernous ICA TA, MRA only revealed aneurysm body, whereas aneurysm neck and distal segment of the parent artery were not revealed. In the remaining cases, MRA clearly depicted aneurysm body and parent artery, whereas the neck was not displayed. ICA TAs showed irregular capsule-like high signal intensity on MRA images. Four TAs exhibited irregular distal segment of the parent artery. TAs at the supraclinoid segment or MCA failed to find fracture signs on nonenhanced CT. CONCLUSIONS: Both CTA and MRA examinations are the effective non-invasive method of imageology for diagnosing intracranial TAs, while CTA is more eligible for diagnosing TAs after nonenhanced CT has demonstrated skull base fractures.