[Protective effect of Apelin-13 on focal cerebral ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the protective effect of Apelin-13 on focal cerebral ischemia-reperfusion injury in rats. METHODS: Focal transient cerebral ischemia-reperfusion injury was induced in male SD rats using modified suture occlusion technique. The rats were randomly divided into 5 groups: Sham group, Model group, Apelin-low dose (A) group, Apelin-middle dose (B) group and Apelin-high dose (C) group. Apelin-13 was injected into lateral cerebral ventricle, and the neurological function score, brain edema, infarct volume, apoptosis, malondialdehyde (MDA), superoxide dismutase (SOD) and extracellular regulated kinase1/2 (ERK1/2) protein were measured. RESULTS: Neurological function scores, percentage of brain water content, infarct volumes and TUNEL-positive cells in B and C groups were lower than those in Model group (P<0.05). The level of MDA in the tissue bomogenate of brain tissue in the surrounding area of ischemia of B and C groups was lower than that of Model group, while the activity of SOD was higher (P<0.05). There was no significant difference in ERK1/2 protein expression among the groups (P>0.05). P-ERK1/2 increased in Model group and A, B, and C groups compared with Sham group (P<0.05), and that of A, B, and C group was higher than that of Model group (P<0.05). CONCLUSION: Apelin-13 may play an important role by inhibiting oxidative stress to protect against focal cerebral ischemia-reperfusion injury; ERK1/2 signaling pathway may be involved in the protective mechanism of Apelin-13.

Cyclin D1 G870A polymorphism and glioma risk in a Chinese population.

BACKGROUND: A number of studies have suggested that the Cyclin D1 (CCND1) G870A polymorphism was associated with susceptibility to various cancers. In the present study, we aimed to investigate the association between CCND1 G870A polymorphism and the risk of glioma in a Chinese population. MATERIALS AND METHODS: CCND1 genotyping was determined by the PCR-RFLP method. The χ (2) test was used to assess for any deviation of the genotype frequencies from Hardy-Weinberg equilibrium and to compare the genotype distributions among glioma patients and healthy control subjects. We calculated the odds ratios (ORs) and 95% confidence intervals (95% CIs) by using unconditional logistic regression. RESULTS: The A allele frequency was higher in cases than that in controls (49.40% vs. 36.39%), and this difference was statistically significant (P = 0.001). Using the G allele as the reference allele, the subjects carrying the A allele had 3.926-fold increase in the risk of glioma (95% CI, 2.172-7.889), and p-value was significant (P = 0.007). Compared to individuals with the GG genotype, individuals with the AA genotype exhibited significantly increased glioma risk (OR = 3.661, 95% CI: 1.658-6.287, P = 0.01). CONCLUSION: Our results suggest that the CCND1 G870A polymorphism may contribute to the susceptibility to glioma in Chinese population.

Anticonvulsant and Sedative Effects of Eudesmin isolated from Acorus tatarinowii on mice and rats.

This paper was designed to investigate anticonvulsant and sedative effects of eudesmin isolated from Acorus tatarinowii. The eudesmin (5, 10, and 20 mg/kg) was administered intraperitoneally (i.p.). The maximal electroshock test (MES) and pentylenetertrazole (PTZ)-induced seizures in male mice were used to evaluate anticonvulsant activities of eudesmin, and sedative effects of eudesmin were evaluated by pentobarbital sodium-induced sleeping time (PST) and locomotor activity in mice. Finally, the mechanisms of eudesmin were investigated by determining contents of glutamic acid (Glu) and gamma-aminobutyric acid (GABA) in epileptic mice, and expressions of glutamate decarboxylase 65 (GAD65), GABAA , Bcl-2, and caspase-3 in the brain of chronic epileptic rats. Results of MES and PTZ tests revealed that eudesmin possesses significant anticonvulsant effects, and the PST and locomotor activity tests demonstrated that eudesmin has significant sedative effects. Furthermore, our study revealed that after treatment with eudesmin, GABA contents increased, whereas Glu contents decreased, and ratio of Glu/GABA decreased. Our results also indicated that expressions of GAD65, GABAA, and Bcl-2 were up-regulated by treating with eudesmin, whereas the caspase-3 obviously was down-regulated. In conclusion, eudesmin has significant anticonvulsant and sedative effects, and the mechanism of eudesmin may be related to up-regulation of GABAA and GAD65 expressions, and anti-apoptosis of neuron the in brain.

miR-503 inhibits cell proliferation and invasion in glioma by targeting L1CAM.

Deregulated microRNAs and their roles in tumorigenesis have attracted much attention in recent years. Although miR-503 has been reported to be aberrant expression in several cancers, its role in glioma remains unknown. In this study, we focused on the expression and mechanisms of miR-503 in glioma development. We found that miR-503 was downregulated in glioma cell lines and tumor tissues, and the restoration of miR-503 reduced cell proliferation invasion. Furthermore, bioinformatics analysis indicated that L1CAM was a putative target of miR-503. In a Luciferase reporter system, we confirmed that L1CAM was a direct target gene of miR-503. These findings indicate that miR-503 suppresses glioma cell growth by negatively regulating the expression of L1CAM. Collectively, our data identify the important roles of miR-503 in glioma pathogenesis, indicating its potential application in cancer therapy.

Neuroprotective effects of trans-caryophyllene against kainic acid induced seizure activity and oxidative stress in mice.

Trans-caryophyllene (TC), a component of essential oil found in many flowering plants, has shown its neuroprotective effects in various neurological disorders. However, the effects of TC on epilepsy haven't been reported before. In this study, we investigated the effect of TC on kainic acid-induced seizure activity caused by oxidative stress and pro-inflammation. We found that TC pretreatment significantly decreased seizure activity score compared to kainic acid treated group. Importantly, TC pretreatment leads to lowering the mortality in kainic acid treated mice. In addition, TC was found to significantly inhibit KA-induced generation of malondialdehyde. TC pretreatment also preserved the activity of GPx, SOD, and CAT. Notably, our data shows that an important property of TC is its capacity to exert cerebral anti-inflammatory effects by mitigating the expression of proinflammatory cytokines, such as TNF-α and IL-1ß. These data suggest that TC has a potential protective effect on chemical induced seizure and brain damage.

Progesterone alters Nogo-A, GFAP and GAP-43 expression in a rat model of traumatic brain injury.

Previous studies have demonstrated that progesterone has neuroprotective effects in the central nervous system (CNS) following traumatic brain injury (TBI). Numerous cellular mechanisms have been reported to be important in the neuroprotective effects of progesterone, including the reduction of edema, inflammation and apoptosis, and the inhibition of oxidative stress. However, the effect of progesterone on neuronal protection following TBI remains unclear. The present study aimed to investigate the effects of progesterone on the expression of Nogo-A, an inhibitor of axonal growth, glial fibrillary acidic protein (GFAP), a main component of the glial scar and growth-associated protein-43 (GAP-43), a signaling molecule in neuronal growth in TBI rats. The TBI model was produced by the weight drop method. In total, 75 rats were assigned to three groups: the sham group, TBI group with vehicle treatment and TBI group with progesterone treatment. The protein expression of Nogo-A, GFAP and GAP-43 in the cortex and the hippocampus was examined by immunocytochemistry. TBI rats significantly increased the expression of Nogo-A, GFAP, and GAP-43 at 1, 3, 7 and 14 days post-injury. Progesterone significantly decreased the expression of Nogo-A and GFAP, and upregulated the GAP-43 protein. Our findings suggested that progesterone promotes neuroprotection following TBI by inhibiting the expression of Nogo-A and GFAP, and increasing GAP-43 expression.

Schwann cells differentiated from adipose­derived stem cells for the treatment of brain contusion.

Rapid development of tissue engineering techniques has led to the possibility of treating central nervous injuries with Schwann cells (SCs). However, certain characteristics of SCs, such as a low proliferation ability, greatly restrict their use. The aim of the present study was to investigate whether SCs differentiated from adipose­derived stem cells (ADSC­SCs) could used to promote functional recovery in brain contusion in rat. ADSCs were isolated and expanded from the groin of Sprague­Dawley rats and differentiated into SCs. The ADSC­SCs were transplanted into the contused rat brain and the locomotor function of the rats was assessed. Significant locomotor function recovery was observed in hemiparalyzed rats treated with ADSCs­SCs. In conclusion, transplantation of ADSC­SCs significantly promoted functional recovery following brain contusion.

[Effect of aneurysm clipping on hemorrhage volume in the subarachnoid space].

OBJECTIVE: To evaluate the effect of aneurysm clipping and partial blood clot removal in the subarachnoid space on hemorrhage volume in the subarachnoid space and cerebral vasospasm in patients with different Fisher grades. METHODS: Patients with subarachnoid space hemorrhage (SAH) of Fisher Grades I, II, and III were subdivided into control and treatment groups for comparative studies. The patients with unruptured intracranial aneurysms (UIAs) undergoing aneurysm clipping were also compared with Fisher grade I control subgroup. OxyHb levels in the cerebrospinal fluid and cerebral blood flow volume (CBFV) of the middle cerebral artery (MCA) were measured on days 3, 7, and 13 day after SAH. RESULTS: The patients with UIAs and Fisher Grade I control subgroup showed significant differences in OxyHb levels on day 3 in CBFV of the MCA on days 3 and 7 (P<0.05). In the SAH groups, OxyHb levels increased significantly on day 3 day in the treatment subgroups of Fisher Grades I and II, but declined significantly on days 7 and 13 in Fisher Grade III treatment subgroup as compared with the corresponding control subgroups (P<0.05); in Fisher Grade I group on days 3 and 7 and in Fisher Grade II group on day 7, CBFV of the MCA increased significantly in the treatment subgroups, but in Fisher Grade III group, CBFV decreased significantly on days 7 and 13 compared with the control subgroup (P<0.05). A positive correlation was found between OxyHb levels in the cerebrospinal fluid and CBFV of the MCA (P<0.05). CONCLUSION: For patients with Fisher Grades I and II aneurysms, craniotomy may increase hemorrhage volume in the subarachnoid space and exacerbate cerebral vasospasm, but for Grade III patients, aneurysm clipping and blood clot removal shows beneficial effects in terms of reducing hemorrhage volume and relieving cerebral vasospasm.

Podocalyxin regulates astrocytoma cell invasion and survival against temozolomide.

Increased podocalyxin (PODXL) expression has been associated with a subset of aggressive types of cancer. To the best of our knowledge, the effect of PODXL on astrocytoma cell invasion and survival against chemotherapy agent was investigated for the first time in the present study. Overexpression and knockdown of PODXL were respectively performed in SW1783 (grade III astrocytoma) and U-87 (grade IV astrocytoma; gliobalstoma) cells. PODXL overexpression in SW1783 cells significantly increased cell invasion, matrix metalloproteinase-9 (MMP-9) expression, cell survival against temozolomide-induced apoptotic stress, and phosphorylation of Akt at serine 473 (ser473), which was abolished by the selective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (LY). Knockdown of PODXL in U-87 cells significantly decreased cell invasion, MMP-9 expression, cell survival against temozolomide, and phosphorylation of Akt at serine 473 (ser473), which was further decreased by LY treatment. In conclusion, in the present study it was demonstrated that PODXL promotes astrocytoma cell invasion, potentially through the upregulation of MMP-9 expression in a PI3K-dependent manner. Additionally, PODXL was shown to promote astrocytoma cell survival against temozolomide-induced apoptotic stress by enhancing the activation of the PI3K/Akt survival signaling pathway. This study provides novel insights into the molecular mechanisms underlying astrocytoma progression, cell survival and chemoresistance, and suggests that PODXL may be a potential target for overcoming chemoresistance in astrocytomas.

[Association of chronic hydrocephalus after aneurysmal subarachnoid hemorrhage with transforming growth factor-ß1 levels and other risk factors].

OBJECTIVE: To study the role of transforming growth factor-ß1 (TGF-ß1) levels and other risk factors in the occurrence of chronic hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients treated for aSAH in our hospital between January, 2007 and June, 2012 were divided into non-hydrocephalus group and hydrocephalus group. TGF-ß1 levels in the cerebrospinal fluid (CSF) were compared between the two groups at different time points. A retrospective analysis was conducted to identify the potential risk factors for chronic hydrocephalus, which were subsequently confirmed by Logistic regression analysis. RESULTS: Of the 129 patients enrolled, 16 (12.4%) developed chronic hydrocephalic with an average diagnosis time of 31.6∓17.0 days. In patients with chronic hydrocephalus, TGF-ß1 level in the CSF increased significantly on the 13th day following aSAH (P<0.05). Retrospective analysis showed that the patients with hydrocephalus and those without had significant differences in history of hypertension, times of SAH, Hunt-Hess classification, ventricular expansion, aneurysm position, Fisher classification, ventricular hemorrhage score and intracranial infections (P<0.05). Logistic regression analysis identified ventricular expansion, aneurysm position, Fisher classification, ventricular hemorrhage score and postoperative intracranial infections as significant risk factors for the occurrence of chronic hydrocephalus (P<0.05). CONCLUSIONS: In adult patients with aSAH, the risk factors for chronic hydrocephalus include ventricular expansion, aneurysm position, Fisher classification, ventricular hemorrhage score and postoperative intracranial infections. These risk factors can have greater clinical value than TGF-ß1 levels in the CSF in predicting the occurrence of chronic hydrocephalus following aSAH.

Mammalian target of rapamycin signaling pathway contributes to glioma progression and patients' prognosis.

BACKGROUND: The mammalian target of rapamycin (mTOR) pathway plays an important role in the regulation of cell growth and increasing evidence suggests its dysregulation in tumors. It also implements many other critical cellular functions, including protein degradation and angiogenesis. To date, a correlation between the mTOR pathway in human glioma and patients' prognosis has not been reported. METHODS: To address this question, we carried out an immunohistochemical study of the mTOR upstream and downstream targets phosphorylated Akt (pAkt), phosphorylated S6 ribosomal protein (pS6), and p27, as well as phosphatase and tensin homologue (PTEN) using biopsies from 96 patients with primary glioma. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. RESULTS: Immunostaining revealed that the mTOR pathway was significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grade of patients with glioma. Especially, the positive expression rates of pAkt, cytoplasmic p27, and pS6 were significantly higher in patients with higher grade (P = 0.002, 0.001 and 0.002) and lower KPS score (P = 0.007, 0.005, and 0.008), which were opposite to the nuclear p27 and PENT expression. Statistical analysis showed that patients with glioma expressing pAkt, PTEN, cytoplasmic p27, nuclear p27, and pS6 have different overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.02), WHO grade (P = 0.005), pAkt (P = 0.009), PTEN (P = 0.006), cytoplasm p27 (P = 0.008), nuclear p27 (P = 0.01), and pS6 (P = 0.003) were independent prognosis factors for human glioma. CONCLUSION: These results provide convincing evidence for the first time that the mTOR pathway correlated closely with overall survival of patients with glioma and might be a novel prognostic marker.

[Three-dimensional computed tomograph angiography and neuroendoscope assisted microsurgery for intracranial aneurysm].

OBJECTIVE: To determine the role of 3-dimensional computed tomograph angiography (3D-CTA) and neuroendoscope in intracranial aneurysm, and to analyze its benefits. METHODS: A total of 38 patients with intracranial aneurysm were confirmed by operation. All the patients were examined by 3D-CTA before the operation and surgical simulation was conducted to ensure the location of aneurysm and its relationship with parent aneurysm artery. Endoscopy was used as an adjunct before and after the microsurgical treatment to observe the neck anatomic features and perforating branches and to verify the optimal clipping position. RESULTS: Pre-operative 3D-CTA clearly displayed the aneurysm and their relation with the parent aneurysm artery, the aneurysm, the periphery vessel, and bony structures, according to demonstration during the operation. Endoscope clearly showed the anatomy around aneurysm, especially the perforating branches. Postoperative 3D-CTA showed satisfactory aneurysm clipping. CONCLUSION: Simulation surgery of 3D-CTA is helpful in finding and exposing aneurysm. Neuroendoscope is very useful for protecting deep blood vessels. Combination of the two can increase the operation success ratio and reduce postoperative complications.

[Role of matrix metalloproteinase in transformation of subdural effusion into chronic subdural hematoma].

OBJECTIVE: To investigate the role of matrix metalloproteinase (MMP) in the transformation of subdural effusion into chronic subdural hematoma. METHODS: The clinical data of 8 patients with subdural effusion that transformed into chronic subdural hematoma were collected and MMP-2 and MMP-9 levels were detected in the sudural effusion, chronic subdural hematoma and capsules of hematoma using gelatin-zymography. RESULTS: MMP-2 and MMP-9 increased significantly in chronic subdural hematoma as compared with those in subdural effusion (P<0.01), and their levels were also significantly higher in the outer membrane than in the inner membrane of hematoma. CONCLUSION: Subdural effusion is a risk factor for the occurrence of chronic subdural hematoma, in which process MMP plays a role as the promoting factor acting primarily in the outer membrane of the hematoma.

[Effect of endogenous brain derived neurotrophic factor on GAP-43 expression in the anterior horn of the spinal cord in rats with sciatic nerve injury].

OBJECTIVE: To investigate the effect of endogenous brain derived neurotrophic factor (BDNF) on GAP-43 expression in the anterior horn of the spinal cord in rats following sciatic nerve injury. METHODS: BDNF antibody was injected intraperitoneally in rats with crushing injury of the sciatic nerve, and the control rats received normal saline only after sciatic nerve injury. At 7 and 14 days after the injection, the expression of GAP-43 in the anterior horn of the corresponding segments of the spinal cord was detected by Western blot and RT-PCR. RESULTS: The expressions of GAP-43 protein and mRNA in the anterior horn of the spinal cord were significantly down-regulated in rats with BDNF antibody injection as compared with those in the control group (P<0.01). CONCLUSION: Endogenous BDNF may regulate the expression of GAP-43 in the spinal cord anterior horn after sciatic nerve injury in rats.

[CT angiography-based simulation of the surgical approach in early operation for ruptured aneurysm].

OBJECTIVE: To simulate the surgical approaches for intracranial aneurysms using three-dimensional CT angiography (3D-CTA) and assess the value of 3D-CTA in early microneurosurgery for ruptured intracranial aneurysms. METHODS: Forty-eight patients with spontaneous subarachnoid hemorrhage due to ruptured intracranial aneurysm were confirmed by early operation. All the patients were classified according to Hunt-Hess, including 11 of grade I, 29 of grade II, and 8 of grade III. CTA was performed before the operation and surgical simulation was conducted. The preoperative findings on CTA and the intraoperative findings were compared and the clinical value of cerebral 3D-CTA was analyzed. RESULTS: Pre-operative 3D-CTA clearly displayed the location, size and shape of the aneurysms, the axis direction of the aneurysm apex and the width of aneurysm neck. The spatial relation between the parent aneutysm artery, the aneurysm, the peripheral vessels and the bony structures were also demonstrated. These findings were basically consistent with the intraoperative findings. The Glasgow outcome score was 5 in 41 patients, 4 in 4 patients, 3 in 2 patients, and 2 in 1 patient upon discharge from the hospital. CONCLUSIONS: Preoperative 3D-CTA examination can simulate the surgery for ruptured aneurysms to help improve the surgical success rate.

[Endoscopic surgery for hypertensive cerebral hemorrhage].

OBJECTIVE: To evaluate the use of endoscopic surgery for hypertensive cerebral hemorrhage. METHODS: Sixteen patients with hyertensive intracerebral hematoma were evacuated with neuroendoscope. The surgical invasive markers, volume of remaining hematoma, and prognosis were compared with those of 19 comparable patients undergoing conventional craniotomy. RESULTS: Complete evacuation of hematoma was achieved in 9 patients, and partial evacuation in 7. All patients were followed up for 6 months. According to GOS, the result was excellent in 6 patients, good in 6, fare in 2, poor and dead in one respectively. The volume of remaining hematoa and invasive markers significantly decreased (P < 0.05); No difference was found in prognosis between the two groups (P > 0.05). CONCLUSION: Neuroendoscopic surgery for hypertensive intracerebral hematoma is characterized by mini-invasion, time-saving, and direct-vision, and is a new approach in this field.