Shuanglin Fu

Ischemic preconditioning induces chaperone hsp70 expression and inhibits protein aggregation in the CA1 neurons of rats

ObjectiveTo investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism.MethodsTwo-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10-min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions.ResultsHistological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region (P < 0.01 vs 10-min ischemia group). Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates (P < 0.01 vs 10-min ischemia group).ConclusionIschemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death.摘要目的研究预缺血对蛋白伴侣hsp70表达和蛋白聚集物形成的影响, 探讨其可能的脑保护机制。方法采用大鼠双侧颈总动脉暂时夹闭法建立全脑缺血模型。 大鼠分为3 min 缺血组, 10 min缺血组以及预缺血组。 苏木素-伊红染色, 光镜下随机计数分析预缺血后海马CA1区死亡神经元数量变化。 免疫组织化学及激光扫描共聚焦显微镜法观察蛋白伴侣hsp70 在CA1区神经元内的分布。 差速离心分离细胞浆、 细胞核及蛋白聚集物。 蛋白印迹法检测不同缺血状态下海马CA1神经元内蛋白聚集物含量的变化, 以及胞浆、 胞核及蛋白聚集物内蛋白伴侣hsp70含量的变化。结果组织学检查显示预缺血能够显著减少海马CA1区神经元死亡数量。 预缺血诱导海马CA1区神经元内蛋白냩侣hsp70 在再灌注后24 h表达。 预缺血处理后, 海马CA1区神经元内蛋白聚集物显著减少。 预缺血诱导的蛋白伴侣hsp70与再缺血形成的异常蛋白结合在一起并防止其聚集。结论预缺血可能通过诱导蛋白伴侣hsp70的表达和抑制再缺血后蛋白聚集物的形成, 减少再缺血引起的神经元死亡。To investigate the effect of ischemic preconditioning on chaperone hsp70 expression and protein aggregation in the CA1 neurons of rats, and to further explore its potential neuroprotective mechanism. Two-vesseloccluded transient global ischemia rat model was used. The rats were divided into sublethal 3-min ischemia group, lethal 10-min ischemia group and ischemic preconditioning group. Neuronal death in the CA1 region was observed by hematoxylineosin staining, and number of live neurons was assessed by cell counting under a light microscope. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of chaperone hsp70 in the CA1 neurons. Differential centrifuge was used to isolate cytosol, nucleus and protein aggregates fractions. Western blot was used to analyze the quantitative alterations of protein aggregates and inducible chaperone hsp70 in cellular fractions and in protein aggregates under different ischemic conditions. Histological examination showed that ischemic preconditioning significantly reduced delayed neuronal death in the hippocampus CA1 region (P < 0.01 vs 10-min ischemia group). Sublethal ischemic preconditioning induced chaperone hsp70 expression in the CA1 neurons after 24 h reperfusion following 10-min ischemia. Induced-hsp70 combined with the abnormal proteins produced during the secondary lethal 10-min ischemia and inhibited the formation of cytotoxic protein aggregates (P < 0.01 vs 10-min ischemia group). Ischemic preconditioning induced chaperone hsp70 expression and inhibited protein aggregates formation in the CA1 neurons when suffered secondary lethal ischemia, which may protect neurons from death. 研究预缺血对蛋白伴侣hsp70表达和蛋白聚集物形成的影响, 探讨其可能的脑保护机制。 采用大鼠双侧颈总动脉暂时夹闭法建立全脑缺血模型。 大鼠分为3 min 缺血组, 10 min缺血组以及预缺血组。 苏木素-伊红染色, 光镜下随机计数分析预缺血后海马CA1区死亡神经元数量变化。 免疫组织化学及激光扫描共聚焦显微镜法观察蛋白伴侣hsp70 在CA1区神经元内的分布。 差速离心分离细胞浆、 细胞核及蛋白聚集物。 蛋白印迹法检测不同缺血状态下海马CA1神经元内蛋白聚集物含量的变化, 以及胞浆、 胞核及蛋白聚集物内蛋白伴侣hsp70含量的变化。 组织学检查显示预缺血能够显著减少海马CA1区神经元死亡数量。 预缺血诱导海马CA1区神经元内蛋白냩侣hsp70 在再灌注后24 h表达。 预缺血处理后, 海马CA1区神经元内蛋白聚集物显著减少。 预缺血诱导的蛋白伴侣hsp70与再缺血形成的异常蛋白结合在一起并防止其聚集。 预缺血可能通过诱导蛋白伴侣hsp70的表达和抑制再缺血后蛋白聚集物的形成, 减少再缺血引起的神经元死亡。

Large cystic hypoglossal schwannoma with fluid-fluid level: a case report.

Hypoglossal schwannomas are rare skull base tumors. Furthermore, cystic hypoglossal schwannomas are extremely uncommon. We report the first case of a large cystic hypoglossal schwannoma with a fluid-fluid level. A 36-year-old woman presented with increased intracranial pressure and cerebellar signs without hypoglossal nerve palsy. Magnetic resonance imaging showed a predominantly cystic mass with a fluid-fluid level in the foramen magnum region extending into the hypoglossal canal. The intracranial tumor was largely removed via a midline suboccipital subtonsillar approach, leaving only a tiny residue in the hypoglossal canal. Histology confirmed a schwannoma with relative hypervascularity. Twenty months later, the tumor recurred and presented as a multicystic dumbbell-shaped lesion, extending intra- and extracranially through the enlarged hypoglossal canal. A complete resection of the intracranial and intracanalicular parts of the tumor was achieved with a small extracranial remnant treated by radiosurgery. Histology revealed a focal increased K(i)67 proliferative index. In this report, we discuss the possible reasons for the absence of hypoglossal nerve palsy and the potential mechanism of the formation of the fluid-fluid level, and we consider the treatment of this lesion.

Diffuse scalp malignant peripheral nerve sheath tumor with intracranial extension in a patient with neurofibromatosis type 1

We describe a rare scalp malignant peripheral nerve sheath tumor (MPNST) with cranial destruction and intracranial extension in a 52-year-old male with neurofibromatosis type 1 (NF1). The scalp tumor measured 22cm×18cm, with local surface ulceration. Skin examination revealed many café-au-lait spots and small, hard dermal nodules on the trunk. CT scans revealed the scalp tumor to have heterogeneous density with partial destruction of the right parietal cranium; on T1-weighted MRI the scalp tumor displayed heterogeneous hypointensity, whereas on T2-weighted and fluid-attenuated inversion recovery MRI it was hyperintense. The tumor was excised totally and the scalp reconstructed using a skin flap isolated from the lateral aspect of the left thigh. Histological examination confirmed that the tumor was an MPNST. The patient recovered uneventfully and was well at the 6-month follow-up, with no local or other tumor recurrence noted.

Autophagy: A strategy for malignant gliomas’ resistance to therapy

Gliomas are malignant primary brain tumors with high morbidity. This tumor has a feature of resistance to chemotherapy and radiotherapy and the underlying mechanism is not yet clear. Autophagy is an evolutionarily conserved process of cytoplasm and cellular organelle in lysosome degradation. Under poor conditions, cells use autophagy to recycle cellular components to sustain metabolism and to prevent the accumulation of damaged, toxic proteins and organelles. More and more recent experimental results suggest that autophagy allows tumor cells survive gene therapy, chemotherapy or nutrient deficient environment. Therefore, we propose the hypothesis that autophagy may be one of the factors influencing on malignant gliomas resistance to therapy. Although there is not yet reaching an agreement about the effects of autophagy on tumor cells survival and death and much more studies are needed to prove the effects of autophagy on malignant gliomas, it gives us a new direction to investigate the mechanism underlying therapy resistance of malignant gliomas.

Drug therapy for chronic subdural hematoma: Bench to bedside

Chronic subdural hematoma (CSDH) is a common neurosurgical condition. Currently, surgery is the most effective medical intervention for treatment of this disorder. Because CSDH is an inflammatory angiogenic disease involving multifactorial mechanisms, a better understanding of CSDH pathogenesis should facilitate clinical management. Therefore, the purpose of this review is to describe recent progress in elucidation of molecular mechanisms causing CSDH and to summarize the body of knowledge gained from past drug treatment studies. Because hematoma fluid and outer membrane characteristics may be linked to pathology, they could serve as disease biomarkers. Moreover, past drug treatment studies have shown that such biomarkers may mutually synergize to initiate and promote CSDH progression. These findings suggest that modulation of biomarker expression or function using drug therapy may benefit CSDH patients.

Transoral penetrating craniocerebral injury by a bamboo chopstick in a child

We present a 3-year-old girl with a transoral injury by a bamboo chopstick penetrating the middle skull base. The features of imaging are described and the management is discussed. The potential for injury to the cavernous sinus is emphasized, even if no there is no hemorrhage on the initial CT scan. Early intracranial infection in relation to penetrating injuries is a factor in planning treatment by craniotomy.

Malignant Cerebral Swelling After Cranioplasty due to Ipsilateral Intracranial Vasculopathy: Case Report and Literature Review

BACKGROUND Cranioplasty is a well-established surgical operation that is used worldwide for patients with skull defects following decompressive craniectomy (DC). However, in some cases, potentially fatal complications may occur, such as malignant cerebral swelling after uneventful cranioplasty. CASE DESCRIPTION We present a rare case of massive malignant ipsilateral cerebral swelling following uneventful titanium mesh cranioplasty due to rare ipsilateral intracranial vasculopathy confirmed by magnetic resonance angiography (MRA) and magnetic resonance venography (MRV). Fortunately, we performed titanium mesh explantation and extended DC in time, and the patient survived. Malignant cerebral swelling after uneventful cranioplasty is an unpredictable but fatal complication. Most reported cases have had an unfavorable prognosis. To the best of our knowledge, the mechanism was first confirmed by MRA and MRV, which demonstrated that the cerebral swelling was due to unilateral intracranial vasculopathy, including a rare ipsilateral intracranial internal carotid artery occlusion, as well as extremely thin lateral and sigmoid sinuses. CONCLUSIONS Our case demonstrates for the first time that ipsilateral intracranial vasculopathy is a risk factor for malignant cerebral swelling after cranioplasty. Patients with traumatic brain injury with suspected intracranial vasculopathy should undergo a comprehensive vascular evaluation before cranioplasty to help prevent malignant cerebral swelling.

Use of a New Type of Trocar for the Surgical Treatment of Hydrocephalus: A Simple and Effective Technique

This study compared the use of a new type of peritoneocentesis trocar with conventional laparotomy for the placement of the distal catheter in the treatment of hydrocephalus with ventriculoperitoneal shunt. A total of 376 patients with hydrocephalus were recruited to the study and were assigned randomly to undergo insertion of the distal catheter by conventional laparotomy (n = 195) or using the new peritoneal trocar (n = 181). The time taken for the surgical procedure and the complication rate over the following 1-year period were compared between the two groups. The mean length of the procedure to place the distal catheter was significantly shorter in the trocar group compared with the laparotomy group. Infection and obstruction rates were significantly higher in the laparotomy group than in the trocar group. In conclusion, the use of the new trocar was associated with lower rates of surgically induced trauma and complications compared with conventional laparotomy.

Pilomyxoid astrocytoma in cerebellum

Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma, and typically locates in the hypothalamic and chiasmatic region. Herein, we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum. MRI scanning showed a tumor involved the cerebellar vermis, tonsil, the forth ventricle and brainstem. It was homogeneous isointensity on T1WI, relative hyper-intensity on T2WI, hyper-intensity on fluid attenuated inversion recovery (FLAIR) images, and uniform enhancement on contrast T1WI. The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma. Follow-up at the 5th month, MRI showed the residual tumor enlarged at the brainstem. The patient survived 10 months after the operation, and finally died of respiration failure resulting from brainstem dysfunction.

Partial titanium mesh explantation cured post-cranioplasty implant-associated scalp infection

Titanium mesh cranioplasty is routinely used worldwide for skull defect patients given its advantages, such as stability and biocompatibility. However, there are very few reports concerning the treatment of implant-associated scalp infection, which is one of the most common complications. The aim of the study is to retrospectively evaluate a novel operation technique for the treatment of titanium mesh-associated scalp infection post-cranioplasty, namely partial titanium mesh explantation (PTME). A retrospective study was conducted in all patients who underwent surgical treatment for implant-associated scalp infection from January 2012 to September 2016 in our hospital. In total, 17 patients were selected for study analysis among 231 patients who underwent cranioplasty. The treatment success rate of PTME was 85.7%. There was no statistically significant difference in demographics and characteristics except for follow-up length of time between the PTME group and TTME (total titanium mesh explantation) group (Non-paired Students t-test, P=0.037). While, The PTME group exhibited a significantly reduced skull defect area post-operation compared with the TTME group (Non-paired Students t-test, P=0.002). Moreover, post-PTME skull area also exhibited a significantly reduced skull defect area compared with the pre-cranioplasty area in the same patient (Non-paired Students t-test, P=0.006). Compared with traditional surgical treatment of implant-associated scalp infection, PTME combined with strict debridement and antibiotic therapy can cure implant-associated scalp infection. Moreover, PTME could preserve sufficient titanium mesh for brain protection and cosmesis.