Volume 36 · Issue 05 · 2020

The incidence of intracranial aneurysms in the general population is about 3% ~5%, and the probability of aneurysm rupture in patients every year is about 0.95%^[1]。 However, once an aneurysm ruptures and develops subarachnoid hemorrhage (SAH), the fatality rate can reach 40%^[2]。 Therefore, timely intervention for intracranial aneurysms is very important. Currently, the safety and efficacy of endovascular therapy for intracranial aneurysms have been studied by the International Study of Unruptured Intracranial Aneurysms (international study of unrup-tured intracranial aneurysms, ISUIA)^[3]And the International Subarachnoid Hemorrhage Aneurysm Trial (international subarachnoid aneurysm trial, ISAT)^[4]And many other large-scale clinical trial studies have confirmed. However, endovascular treatment of complex intracranial aneurysms (such as giant aneurysms, wide-neck aneurysms, fusiform aneurysms and dissecting aneurysms, etc.) is still a great challenge because of its complex treatment process, high complication rate and high recurrence rate after treatment^[5]。 In recent years, with the emergence of flow diverter (FD), clinicians and patients have more treatment options. FD is a blood flow remodeling device developed on the basis of hemodynamic study of intracranial aneurysms. Its appearance has changed the concept of endovascular treatment of intracranial aneurysms, and shifted the previous intracapsular embolization to the reconstruction of tumor-bearing artery. Because it has a finer mesh and stronger blood flow guidance ability than ordinary intracranial stents, it is more conducive to the transitional growth of arterial endothelial cells and the covering and closure of tumor neck^[6]。 Through the design of high metal coverage and high mesh ratio of FD, the local blood flow is remodeled, and the impact blood flow from the tumor-bearing artery to the aneurysm is guided into the distal normal blood vessel, thus reducing the impact of local blood flow to the aneurysm, improving the hemodynamic condition in the aneurysm, and finally forming thrombosis in the aneurysm, thus realizing the occlusion of the aneurysm^[7]。

To study the gene mutation characteristics of neurofibromatosis type 2 (NF2) in children and to analyze its clinical features.

From January 2015 to July 2018, 12 children diagnosed with NF2 (children′s group) were treated at Department of Neurosurgery, the First Center of Chinese PLA General Hospital and enrolled into this retrospective study, and 20 adult patients of NF2 (adult group) admitted during the same period served as control group. The age of onset, age of diagnosis, latency to diagnosis, initial symptoms, NF2-related lesions, NF2-affected systems, number of surgical interventions and other clinical data were compared between the 2 groups. The peripheral blood samples of 25 patients (7 others were sequenced in other hospitals) and 41 direct relatives of the patients underwent whole exome sequencing. In addition, the preli-minary screening of common gene mutations was carried out. We compared the difference in NF2 gene mutation types and severity grades between children and adult groups.

Compared with the adult group, the age of onset (33.4±8.3 years old vs. 11.3±4.4 years old, P< 0.001) and the age of diagnosis (37.6±8.4 years oldvs. 18.9±4.4 years old, P<0.001) in the children group were earlier than those in the adult group, and the average latency to diagnosis (7.6±4.3 yvs. 4.2±3.0 y, P=0.014) was longer than that in the adult group. In terms of initial symptoms, the numbers of cases with non-hearing related symptoms (9/12 vs. 3/20, P=0.002) and cases with skin symptoms (6/12 vs. 1/20, P=0.006) were more than those in the adult group. The proportion of non-vestibular schwannoma(6/12 vs. 1/20), spinal cord lesions(9/12 vs. 4/20), and skin lesions(10/12 vs. 4/20) in the children group was higher than those in the adult group (all P<0.01). There were more disease-affected systems in children than adults(P<0.001). The number of NF2 related interventions was 1.2±0.7 in the adult group and 2.3±1.2 in the children group, and the difference between the 2 groups was statistically significant (P=0.002). In terms of NF2 gene mutations, the proportion of nonsense mutations (6/12 vs. 3/20, P=0.049), truncated mutations (7/12 vs. 3/20, P=0.018) and gene mutation grade 3 (7/12 vs. 3/20, P=0.018) in the children group were higher than those in the adult group.

It is preliminarily concluded that the onset age of childhood NF2 seems earlier and the latency to diagnosis is longer, which, in addition, more commonly presents atypical symptoms such as skin-related ones, affects multiple systems and has high gene mutation grade. Therefore, active intervention and long-term management plan are needed.

To explore the clinical characteristics and surgical outcomes of patients with mixed gangliocytoma-pituitary adenoma.

We retrospectively reviewed the clinical profiles from 23 patients with mixed gangliocytoma-pituitary adenoma admitted to Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University between January 2006 and November 2019. All 23 patients underwent surgical resection via transnasal transsphenoidal approach . Postoperative cranial MRI was performed to determine the extent of tumor resection. Immunohistochemical staining of tumor tissue samples obtained during operation was performed. All patients were followed up at the outpatient clinic for cranial MRI and endocrine reexamination to determine tumor recurrence. Kaplan-Meier survival analysis was conducted to investigate all patients′ overall survival (OS) and progression-free survival (PFS).

Postoperative cranial MRI indicated that total resection was achieved in 19 cases (82.6%) and subtotal resection in 4 (17.4%). Postoperative pathological examination showed that all cases were classified as mixed gangliocytoma-pituitary adenoma (WHO Ⅰ). Of those, there were 3 (13.0%) cases of growth hormone (GH) subtype, 1 (4.4%) case of prolactin (PRL) subtype, 6 (26.1%) cases of PRL-GH subtype, 10 (43.5%) cases of silent subtype and 3 (13.0%) cases of null cell subtype. Neuronal marker staining was applied in 11 patients and the results showed that synaptophysin was positive in 8 cases (8/8), neurofilament proteins positive in 6 (6/6), neurofilament protein positive in 3 (3/3), chromogranin A positive in 3 (3/3) and microtubule-associated protein 2 positive in 1 (1/1). Besides, 2 cases underwent transcriptional factor examination and both were positive in pituitary-specific transcription factor 1 (Pit-1). The median follow-up time of 23 patients was 54 months (5-113 months). There were 4 cases (17.4%) of recurrence and 1 case of death during follow-up. The 10-year PFS and OS rate were 79.1% and 94.4% respectively, which was suggested by Kaplan-Meier survival analysis.

The clinical manifestations of mixed neuroblastoma-adenoma are not specific and its diagnosis is confirmed by postoperative pathological results. Surgical resection via transsphenoidal approach seems to be the main treatment method and most patients could have a relatively good outcome.

To explore the effect of repetitive transcranial magnetic stimulation (rTMS) on the recovery of motor dysfunction in patients with gliomas involving the supplementary motor area (SMA).

The clinical data and follow-up results of patients with lower-grade gliomas involving SMA who presented postoperative motor dysfunction were retrospectively analyzed. A total of 5 patients underwent surgical treatment at Department of Neurosurgery, Beijing Tiantan Hospital from October 2018 to December 2019 and were enrolled in this study. All patients underwent awake craniotomy. During operation, neuronavigation and direct electrical cortical stimulation were performed to identify the anatomical boundaries of tumor and motor cortices, and resection was further performed. The patient's motor function recovery was documented dynamically on the first day after surgery, and at least 3 rTMS treatments were initiated on the 7th day after surgery, with a total treatment time of 2 weeks. All patients did not undergo radiotherapy or chemotherapy during rTMS therapy. Muscle strength was evaluated according to the sacle set by Medical Research Council (MRC) of the United Kingdom

Of the 5 glioma patients, 2 underwent complete resection and 3 underwent partial resection. Postoperative histopathological results showed that there were 2 cases of oligodendroglioma, 2 cases of astrocytoma and 1 case of anaplastic oligodendroglioma. After surgery, 4 patients developed hypertonic dyskinesia, i. e. SMA syndrome, and 1 patient developed hypotonic dyskinesia. After rTMS treatment, the motor function recovery time of 4 patients with SMA syndrome was 14.0±2.3 d (9-20 d) whose motor function was restored to preoperative level within 1 month. Motor function of the patient with hypotonic dyskinesia did not return to preoperative level within 2 month post surgery.

This study suggests that the technique of rTMS can speed up the recovery of motor function in glioma patients with postoperative SMA syndrome and provide new ideas for postoperative motor function rehabilitation in such patients.

To construct a Cox proportional hazards regression model of glioma based on the Cancer Gene Atlas (TCGA) project database, and to validate it in Chinese Glioma Genome Atlas (CGGA) project database and explore its value in prognosis prediction.

The clinical data and RNA sequencing data of 668 glioma patients (experimental group) along with 5 control samples in the TCGA database and 619 glioma patients in the CGGA database (validation group) were retrospectively analyzed. We screened the differential genes between glioma samples and normal tissues in the TCGA database. Cox regression method was used to establish the risk model in the experimental group. In the experimental and validation groups, Kaplan-Meier method was used to draw survival curves and log-rank method was used to test the difference of survival time between high and low risk patients. Univariate and multivariate Cox regression models were used to analyze the prognostic factors of glioma patients. Independent prognostic factors were included in the analysis and a nomogram was drawn. The genes that were highly expressed in the high-risk group were used for gene enrichment analysis of gene ontology (GO).

There was no statistically significant difference in age (<40 years or ≥ 40 years), gender or survival time between the experimental and validation groups (allP>0.05), while there were statistically significant differences in WHO grade classification, pathological type distribution, andIDH1/2 mutation rate (all P<0.05). A total of 10 genes (SHD,MRC2, RPLP0P6, HOXA5, SULF2, FOXJ1, CDKN2A, NKX2-5, PLEKHA4 and CDK4) were screened for the construction of Cox regression model. The model risk value > 0.646 was considered as high risk and that ≤0.646 as low risk. The 1-, 3- and 5-year survival rates of the high risk patients in the experimental group were 66.2%, 27.7%, and 17.8% respectively, while those of the low risk patients were 98.4%, 88.2%, and 73.6% respectively. The 1-, 3- and 5-year survival rates of the high risk patients in the validation group were 69.0%, 40.1%, and 30.6% respectively, while those of the low risk patients were 91.0%, 76.7%, and 63.3% respectively. The survival time had statistically significant difference between the high and low risk categories for both experimental group and validation group(all P<0.05 ). The results showed that age ≥40 years (HR=3.031, 95%CI: 2.152-4.269, P<0.001), WHO grade Ⅳ (HR=1.961, 95%CI: 1.494-2.575, P<0.001), and Cox proportional hazards regression model risk with high risk (HR=3.100, 95%CI: 1.915-5.020, P<0.001) were independent risk factors for prognosis, and those were used to construct a nomogram of individual assessment to predict the 1-, 3-, and 5-year survival probability of patients.The predicted results of the nomogram were highly consistent with patients′ prognosis, and the consistency index was 0.844. The GO function enrichment analysis showed that the over-expressed genes in the high-risk group were closely related to 13 functions of tumor microenvironment and immune regulation.

The Cox proportional hazards regression model and nomogram based on transcriptome sequencing data may provide value in predicting the prognosis of glioma patients.

To explore the treatment regimen and outcome of tuberous sclerosis complex (TSC) with subependymal nodule (SEN)/subependymal giant cell astrocytoma (SEGA).

The clinical data of 12 children with TSC with SEN/SEGA admitted to Department of Neurosurgery, Beijing Children′s Hospital Affiliated to Capital Medical University from April 2010 to March 2019 were retrospectively analyzed in this case-series study. The imaging findings in 12 cases showed typical space-occupying lesions in the vicinity of the foramen mencius. Among them, 6 cases that were considered as SEN underwent no surgical treatment, and out of the other 6 cases considered as SEGA, 5 cases underwent tumor resection (through the approach of frontal cortex fistula in 4 and the transcallosal interforniceal approach in 1) and 1 case refused treatment. The mammalian target of rapamycin (mTOR) inhibitor sirolimus was used in 6 cases. The outcomes of those children were evaluated by outpatient clinical and imaging follow-up.

All 5 children undergoing surgery achieved total resection of the tumor and pathological results indicated SEGA (World Health Organization grade Ⅰ). One case developed hydrocephalus after surgery and then underwent ventriculoperitoneal shunting. The follow-up period of 12 children was 0.5-9.0 years. None of the 5 patients had neurological dysfunction or recurrence at the latest follow-up. Imaging examination of 6 children with SEN showed no enlargement of SEN. The frequency of seizures was reduced by more than 50% in all 6 children treated with sirolimus.

Children with TSC combined with SEN/SEGA are rare. Individualized diagnosis and treatment plan could lead to relatively good clinical outcomes, while further follow-up is still needed for the study of the children’s long-term outcome.

To explore the therapeutic efficacy of comprehensive treatment for the giant tumor involving the third ventricle in infants and young children.

A retrospective analysis was conducted on 16 patients ≤ 3 years old who underwent surgical treatment for giant tumors of the third ventricle at Department of Neurosurgery Center, Tsinghua University Yuquan Hospital from January 2013 to June 2019. Pathological examination indicated that there were 8 cases of germ cell tumor, 4 cases of pineoblastoma, 2 cases of astrocytoma and 2 cases of choroid plexus papilloma. Among them, 8 patients underwent ventriculoperitoneal shunting and 2 underwent ventriculoscopic third ventriculostomy prior to tumor resection. All tumors were resected through transcallosal interforniceal approach. There were 3 patients undergoing neoadjuvant chemotherapy before operation and 10 undergoing adjuvant chemotherapy after operation.

Total removal of the tumor was achieved in all 16 cases. Postoperative complications included subdural effusion in 11 cases and respiratory dysfunction in 3, all of which improved following treatment. Of the 3 children with preoperative chemotherapy, 2 were reduced in tumor volume and 1 increased in tumor volume after chemotherapy, and 3 cases showed that the tumor blood supply was not abundant and local necrosis change was reported. Postoperative pathological examination revealed degeneration and necrosis of focal tumor cells and vascular wall. One case was lost to postoperative follow-up and 15 were followed up for 72 months (median: 18 months). Three cases of pineoblastoma died within 10 months of surgery due to wide dissemination of tumor in the subarachnoid space, and none of the remaining 12 cases had relapsed.

Tumors involving the third ventricle can be safely and totally resected via the transcallosal interforniceal approach. Microsurgical resection can be facilitated by preoperative neoadjuvant chemotherapy for some malignant brain tumors and postoperative chemotherapy may reduce tumor recurrence.

To investigate the effect of arterial embolization-assisted microsurgical resection of large (tumor diameter ≥5 cm) parasagittal meningioma.

Clinical data of 22 patients with large parasagittal meningioma admitted to Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University from January 2013 to March 2019 were retrospectively analyzed. All patients underwent magnetic resonance venography (MRV) to determine the patency of superior sagittal sinus, which showed that 12 cases had occlusion of superior sagittal sinus and 10 cases had patency of superior sagittal sinus. Twelve cases with non-patent superior sagittal sinus underwent digital subtraction angiography (DSA) and embolization of tumor-feeding arteries 1 d before tumor resection (embolization group). Ten cases with patent superior sagittal sinus underwent microsurgical resection (non-embolization group). The degree of tumor resection was assessed by Simpson classification. Clinical and imaging follow-up was performed post operation. Karnofsky performance score (KPS) was used to evaluate the patients’ functional status after surgery. Contrast enhanced MRI scan was performed to detect the tumor recurrence.

All 12 patients in the embolization group achieved Simpson grade Ⅰ resection. In the non-embolization group, Simpson Ⅰ resection was achieved in 2 patients and Simpson Ⅱ resection in 8. There was statistical difference in the degree of tumor resection between the two groups (P<0.001). Bleeding volume during operation in the embolization group was less than that in the non-embolization group (342±138 mlvs. 730±556 ml, P=0.028). There was no statistically significant difference in the incidence of complications (P=0.646) or the recurrence rate (P=0.571) between the two groups. The difference in KPS score at 3 months post operation between the two groups was statistically significant (P=0.195).

The preoperative DSA of patients with large parasagittal meningioma can clearly identify the condition of superior sagittal sinus, and for the tumors that are mainly supplied by the external carotid artery, arterial embolization-assisted microsurgical resection could reduce intraoperative bleeding, help improve surgical safety, and improve the degree of tumor resection.

To summarize the clinical data of patients with acute kidney injury (AKI) during perioperative period of intracranial tumor resection and review the literatures to explore the possible risk factors for perioperative AKI.

We retrospectively analyzed the clinical data of 4 patients with intracranial tumor who developed severe perioperative AKI (accounting for about 0.03% of the patients with intracranial tumor undergoing operation during the same period) at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from January 2016 to December 2018. All 4 patients underwent tumor resection.

Postoperative pathological examination indicated 2 cases of meningioma, 1 case of pituitary adenoma and 1 case of craniopharyngioma. Two patients had hyperglycemia prior to surgery (one patient had a history of diabetes), two patients had intraoperative hypotension, two patients had an operation time >3 h, and three patients were administered nephrotoxic drugs perioperatively.

For patients undergoing intracranial tumor resection, perioperative AKI may be more likely to occur if there are factors including diabetes, hyperglycemia, nephrotoxic drugs, operation time> 3 h, and intraoperative hypotension.

To investigate the mid- and long-term outcomes of flow diversion using with Pipeline embolization device (PED) in treatment of intracranial complex anterior circulation aneurysms.

We retrospectively reviewed the clinical data of 58 intracranial complex anterior circulation aneurysms, including 8 ruptured and 50 unruptured aneurysms, which were treated with PED at Department of Neurosurgery, the First Affiliated Hospital of Xinjiang Medical University from May 2015 to September 2018. The occlusion extent and clinical outcomes were evaluated based on the O′Kelly-Marotta (OKM) grading scale and modified Rankin scale (mRS) respectively.

All 58 patients were successfully implanted with PEDs and immediate post-operative angiography revealed complete occlusion (OKM grade D) in 8 (13.8%) cases. Short-, mid- and long-term follow-ups were conducted at a mean period of 5.8±1.1 months (range: 4-9 months), 12.8±2.1 months (range: 10-18 months) and 33.9±8.3 months (range: 24-52 months) respectively. The results showed that the short-, mid- and long-term complete aneurysm occlusion (OKM grade D) rates were 87.7% (50/57), 98.2% (55/56) and 100.0% (47/47) respectively. Correspondingly, the favorable outcome (mRS: 0-2) rates were 96.6% (56/58), 98.2% (55/56) and 97.9% (46/47) respectively. Of the 8 patients with ruptured aneurysm, there were 7, 6 and 5 patients who underwent short-, mid- and long-term follow-up, and grade D occlusion was observed in 5, 6 and 5 cases respectively. Complications occurred in 13 (22.4%) of 58 patients and 2 (3.4%) died. Among them, there were 2 cases (3.4%) of hemorrhage, 1 case (1.7%) of hydrocephalus, 4 cases (6.9%) of asymptomatic occlusion of branch vessel, 2 cases of decreased vision (1 case with permanent blindness), 3 cases of hematoma at puncture point and 1 case of upper gastrointestinal bleeding.

PED treatment of intracranial complex anterior circulation aneurysm is associated with low incidence of serious complications and high rate of complete occlusion at mid- and long-term follow-up. There seem to be a high rate of occlusion and favorable clinical outcomes for unruptured aneurysms. A relatively high incidence of complications is reported for ruptured aneurysm, and PED should be carefully selected.

To evaluate the safety and efficacy of LEO Baby stent-assisted coiling in the treatment of wide-neck intracranial aneurysms.

Between December 2018 to June 2019, 21 patients with wide-neck intracranial aneurysms were treated with LEO Baby stent-assisted coiling at Department of Cerebrovascular Disease, Zhengzhou University People′s Hospital and retrospectively enrolled into this study. There were 23 aneurysms in those 21 patients. Among them, 5 aneurysms were located on the anterior communicating artery, 10 at the bifurcation of middle cerebral artery, 2 at the M1 segment of middle cerebral artery, 3 at the M2 segment of middle cerebral artery and 3 at the A3 segment of the anterior cerebral artery. The ratio of neck/dome was more than 1/2 in all intracranial aneurysms. Single LEO Baby stent-assisted coiling was used in 22 aneurysms, and the other aneurysms was treated with the Y stent technique (LEO Baby + Neuroform EZ). After the procedure, the immediate DSA was performed to evaluate the aneurysm occlusion and the parent artery patency. The clinical follow-up was performed in all patients for 3 months post discharge. The modified Rankin Scale (mRS) score was used to determine the patient′s outcome and the mRS ≤2 was defined as good outcome. After 6 to 8 months, DSA was performed to evaluate the aneurysm occlusion and stent patency.

A total of 21 patients with 23 aneurysms were all successfully treated. The immediate postprocedural Raymond scale of the aneurysms were assessed which indicated grade Ⅰ in 18 aneurysms (78.3%), Ⅱ in 3 (13.0%) and Ⅲ in 2 (8.7%). The periprocedural complications rate was 9.5% (2/21). Out of the 2 patients with complications, 1 died of severe pulmonary infection, and the other developed cerebral infarction due to the late-onset cerebral vasospasm and the mRS score was 3 at discharge. Twenty patients obtained 3-month clinical follow-up post procedure, and the mRS scores were 1 in 1 patient, 2 in 1 and 0 in the remaining 18. All patients had good outcomes (mRS≤2). Sixteen patients with 17 aneurysms obtained the imaging follow-up lasing for 6.4±0.7 months (range: 6-8 months) post procedure. Of those, 15 aneurysms were Raymond Ⅰ immediately post procedure indicating complete embolization, and the other 2 were Raymond Ⅱ and Ⅲ respectively immediately post surgery, none of which showed any further growth in the tumor neck and dome. No in-stent stenosis or delayed thromboembolic events were noted in 17 patients.

This preliminary study has suggested that LEO Baby stent-assisted coiling seems safe and effective in the embolization of intracranial aneurysms on small-diameter arteries, which can be used as an option for treatment of aneurysms at intracranial bifurcation or far ends of arteries.

To explore the risk factors of infection in infants with hydrocephalus after ventriculoperitoneal shunting.

The clinical data of 427 children with hydrocephalus undergoing ventriculoperitoneal shunting at Neurosurgery Department of the Third Affiliated Hospital of Zhengzhou University from March 2013 to March 2017 were retrospectively analyzed in this study. According to the clinical symptoms at the local site and results of laboratory examination, the presence or absence of infection of the patients was determined. Furthermore, unirariate and multivariate logistic regression analysis were used to investigate the risk factors of postoperative infection.

Of the 427 children, 50 were diagnosed as postoperative infection (infection group) and 377 as non-infection (non-infection group). The clinical manifestations of 50 children with confirmed infection were headache in 11 cases, vomiting in 15, local skin swelling in 7, fever in 12, gait instability in 2 and intestinal obstruction in 3. The results of cerebrospinal fluid or deep swab culture showed that the pathogens were Staphylococcus epidermidis in 31 cases (62.0%), Staphylococcus aureus in 10 (20.0%), gram negative bacilli in 5 (10.0%), and other bacteria in 4 (8.0%). The results of univariate analysis showed that preterm delivery, age, severity of hydrocephalus and operation duration were the influencing factors of postoperative infection (all P<0.05). Further multivariate logistic regression analysis showed that preterm delivery (OR = 3.687, 95% CI: 1.937-7.017, P < 0.001), age ≤ 6 months ( OR = 0.385, 95% CI: 0.155-0.953, P = 0.039), severe hydrocephalus (OR = 0.494, 95% CI: 0.259-0.943, P = 0.033) and operation duration > 1 h ( OR = 0.345, 95% CI: 0.180-0.659, P = 0.001) were independent risk factors for postoperative infection.

The risk factors of infection in children with hydrocephalus after ventriculoperitoneal shunting include preterm delivery history, small age, heavy degree of hydrocephalus and long operation duration.

To investigate the role of bone morphogenetic protein 2(BMP2) signaling pathway in the development of intracranial aneurysms and its mechanism in regulating the apoptosis of vascular smooth muscle cells (VSMCs).

The healthy male SD rats were divided into 2 groups according to the random number table method, which were the model group (n=32) and the sham operation group (n=32). In the model group, the intracranial aneurysm model was established by ligating the left external carotid artery, the left pterygopalatine artery and the right common carotid artery of the rat. The vessels were not ligated in sham operation group. The rats in both groups were sacrificed at 3 months after operation, and the model establishment was judged by electron microscopy observation and hematoxylin-eosin (HE) staining. BMP2 and downstream phosphorylated Smad1/5(p-Smad 1/5) expression in VSMCs of the rats′ anterior communicating artery complex in both groups were detected by immunohistochemical staining and Western blotting respectively. VSMCs of the rat′s cerebral arteries were further cultured in vitro and divided into 3 groups: control group, BMP2 group(add BMP2 100 ng/ml) and Smad6+ BMP2 group(trasfect Smad6 overexpression vector+ add BMP2 100 ng/ml). The apoptosis of VSMCs in each group was detected by TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling), and the expression of Caspase3, BMP2 and downstream phosphorylated Smad1/5 of VSMCs in each group was detected by Western blotting.

Compared with the sham group, the rat′s cerebral arteries had different degrees of lesions in the model group, and VSMCs of the blood vessel wall had obvious remodeling and apoptosis by electron microscopy observation and HE staining, indicating that the disease model was established successfully. The immunohistochemical staining showed that the relative expression levels of Caspase3 (0.25 ± 0.03 vs. 0.06 ± 0.01) and BMP2 (0.12 ± 0.03 vs. 0.06 ± 0.01) were increased significantly in the model group compared with the sham group (both P < 0.05). Compared with the sham group, the Western blotting results showed that BMP2 (0.50 ± 0.04 vs. 0.75 ± 0.07) and p-Smad1/5 (0.27±0.04 vs. 0.73±0.07) relative expression in the model group was increased significantly (both P < 0.05). The TUNEL detection showed that the apoptosis rates of VSMCs in BMP2 group (4.35% ± 0.65% vs. 74.63% ± 6.05%) and Smad6+ BMP2 group (4.35% ± 0.65% vs. 45.92% ± 1.08%) were significantly increased compared with those in the control group (both P <0.01), while the VSMCs apoptosis rate in the Smad6 + BMP2 group was less than that in the BMP2 group ( P < 0.01). Western blotting results showed that the relative expression levels of p-Smad1/5 and Caspase3 in the BMP2 group and Smad6 + BMP2 group were both increased compared with those in the control group (both P < 0.01), while the expression levels of p-Smad1/5 and Caspase3 in the Smad6 + BMP2 group were lower than those in the BMP2 group(both P <0.05).

BMP2 and downstream p-Smad1/5 are closely related to the apoptosis of VSMCs in intracranial aneurysms. The apoptosis of VSMCs mediated by BMP/Smad signaling pathway may be one of the mechanisms of the occurrence and development of intracranial aneurysms.

Professor Luo Shiqi, a famous neurosurgeon, one of the pioneers of neurosurgery in China, and former deputy director of neurosurgery in Beijing Tiantan Hospital, died at 15: 48 on May 3, 2020 in Beijing Tiantan Hospital at the age of 83.