Kaiwei Han

Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia

Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neurons. However, the role of VEGF in the regulation of ischemic brain injury remains unclear. In this study, rats were subjected to MCAO (middle cerebral artery occlusion) followed by intraperitoneal injection of VEGF165 (10 mg/kg) immediately after surgery and once daily until the day 10. The expression of target genes was assayed using qPCR, western blot and immunofluorescence to investigate the role of VEGF165 in regulating ischemic brain injury. We found that VEGF165 significantly inhibited MCAO‐induced up‐regulation of Scavenger receptor class A (SR‐A) on microglia in a VEGFR1‐dependent manner. VEGF165 inhibited lipopolysaccharide (LPS)‐induced expression of proinflammatory cytokines IL‐1β, tumor necrosis factor alpha (TNF‐α) and iNOS in microglia. More importantly, the role of VEGF165 in inhibiting neuroinflammation is partially abolished by SR‐A over‐expression. SR‐A further reduced the protective effect of VEGF165 in ischemic brain injury. These data suggest that VEGF165 suppresses neuroinflammation and ischemic brain injury by inhibiting SR‐A expression, thus offering a new target for prevention of ischemic brain injury.

Management of Penetrating Skull Base Injury: A Single Institutional Experience and Review of the Literature

Background Penetrating skull base injury (PSBI) is uncommon among head injuries, presenting unique diagnostic and therapeutic challenges. Although many cases of PSBIs have been reported, comprehensive understanding of its initial diagnosis, management, and outcome is still unavailable. Materials and Methods A retrospective review was performed for patients treated in neurosurgical department of Changzheng Hospital for PSBIs. Presurgical three-dimensional (3D) Slicer-assisted reconstructions were conducted for each patient. Then we reviewed previous literature about all the published cases of PSBIs worldwide and discussed their common features. Results A total of 5 patients suffering PSBIs were identified. Penetrating points as well as the surrounding neurovascular structures were clearly visualized, assisting in the presurgical planning of optimal surgical approach and avoiding unexpected vascular injury. Four patients underwent craniotomy with foreign bodies removed successfully and 1 patient received conservative treatment. All of them presented good outcomes after proper management. Conclusion Careful physical examination and radiological evaluation are essential before operation, and angiography is recommended for those with suspected vascular injuries. 3D modeling with 3D Slicer is practicable and reliable, facilitating the diagnosis and presurgical planning. Treatment decision should be made upon the comprehensive evaluation of patients clinicoradiological features and characteristics of foreign bodies.

CCNG2 Overexpression Mediated by AKT Inhibits Tumor Cell Proliferation in Human Astrocytoma Cells

The cyclin family protein CCNG2 has an important inhibitory role in cancer initiation and progression, but the exact mechanism is still unknown. In this study, we examined the relationship between CCNG2 and the malignancy of astrocytomas and whether the AKT pathway, which is upregulated in astrocytomas, may inhibit CCNG2 expression. CCNG2 expression was found to be negatively associated with the pathological grade and proliferative activity of astrocytomas, as the highest expression was found in control brain tissue (N = 31), whereas the lowest expression was in high-grade glioma tissue (N = 31). Additionally, CCNG2 overexpression in glioma cell lines, T98G and U251 inhibited proliferation and arrested cells in the G0/G1 phase. Moreover, CCNG2 overexpression could increase glioma cells apoptosis. In contrast, AKT activity increased in glioma cells that had low CCNG2 expression. Expression of CCNG2 was higher in cells treated with the AKT kinase inhibitor MK-2206 indicating that the presence of phosphorylated AKT may inhibit the expression of CCNG2. Inhibition of AKT also led to decreased colony formation in T98G and U251 cells and knocked down of CCNG2 reversed the result. Finally, overexpression of CCNG2 in glioma cells reduced tumor volume in a murine model. To conclude, low expression of CCNG2 correlated with the severity astrocytoma and CCNG2 overexpression could induce apoptosis and inhibit proliferation. Inhibition of AKT activity increased the expression of CCNG2. The present study highlights the regulatory consequences of CCNG2 expression and AKT activity in astrocytoma tumorigenesis and the potential use of CCNG2 in anticancer treatment.

miR-448-3p controls intracranial aneurysm by regulating KLF5 expression

microRNAs (miRNAs) control several processes known to be involved in progression of aneurysm. Here, intracranial aneurysms (IAs) were surgically induced in Sprague-Dawley rats, and we found that miR-448-3p was downregulated and KLF5 was upregulated in IA rats. We identified Klf5 as a direct target of miR-448-3p in smooth muscle cells (SMCs). In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p-treated group. miR-448-3p treatment protected the wall thickness ratio and suppressed macrophage infiltration after IA induction. IAs caused a significant increase in KLF5 expression and were alleviated by miR-448-3p. Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. These data suggest that miR-448-3p plays the inhibitory role in IA progression, indicating that miR-448-3p overexpression is crucial for preventing the development of IA through downregulation of macrophage-mediated inflammation.

Clinical features and management of nonfunctioning giant pituitary adenomas causing hydrocephalus

We evaluated the features of clinically nonfunctioning giant pituitary adenomas (NFGPAs) causing hydrocephalus to highlight the timing of hydrocephalus management and surgical approaches. A total of 24 patients with NFGPAs and hydrocephalus were included. Eighteen patients underwent endoscopic transsphenoidal surgery. Ten patients received pterional surgery, including 6 patients as first treatment and 4 cases with recurrence after transsphenoidal approach. Gross total resection was achieved in 10 patients, including 6 cases (6/18, 33.3%) with endoscopic transsphenoidal surgery and 4 cases (4/10, 40%) with pterional surgery. All patients were divided into preoperative EVD group and non-preopoerative EVD group. The proportion of patients receiving postoperative EVD or shunt was significantly higher in non-preoperative EVD group than that in preoperative EVD group (9/15 vs. 1/9, P = 0.033). Visual impairment score (VIS) was evaluated for each patient. We detected significant vision improvement according to the preoperative and postoperative VIS (median, interquartile range: 62, 48.25–77 vs. 36.5, 0–50.75, P < 0.001). Conclusively, for patients with NFGPAs and hydrocephalus, preoperative EVD might reduce the need for a second shunt or EVD. Surgical approach should be decided based on the clinicoradiological features and surgeons’ experience for individualized treatment, and endoscopic transsphenoidal resection of pituitary adenomas was suggested for most NFGPAs.