Renya Zhan

A prospective study of early versus late craniectomy after traumatic brain injury

Background: Decompressive craniectomy is an important method for managing traumatic brain injury (TBI). At present, controversies about this procedure exist, especially about the optimum operative time for patients with TBI. Methods: A prospective study was performed at the First Affiliated Hospital, College of Medicine, Zhejiang University. From January 2008 to December 2009, 25 patients who underwent early decompressive craniectomy were included in the study group, and 19 patients who underwent “late” decompressive craniectomy as a second-tier therapy for intracranial hypertension were included as a comparison group. Results: The 30-day mortality after the operation was 16% in the study group. The overall mortality rate was 20% at the 6-month follow-up. A total of 52% of the patients (13 patients) had good outcomes, and 7 patients remained in a severely disabled or vegetative state. In the comparison group, 4 patients died, and 12 had good outcomes at the 6-month follow-up. The remaining 3 patients had poor outcomes. The study group was well matched with the comparison group. However, the outcomes in the study group were not better than those in the comparison group, as evaluated by the 6-month GOS score. Conclusion: Early decompressive craniectomy as a first-tier therapy for intracranial hypertension did not improve patient outcome when compared with “late” decompressive craniectomy for managing TBI.

Cranioplasty for patients developing large cranial defects combined with post-traumatic hydrocephalus after head trauma

Background: Large cranial defects combined with hydrocephalus after decompressive craniectomy are a common, harsh reality among patients with head trauma. Typically, a shunt is first used to relieve the hydrocephalus. However, subsequently the patients may develop a severe sinking scalp flap over the skull defect before cranioplasty, which would make the procedure difficult. Methods: This problem was overcome by temporarily adjusting the shunt pressure using a programmable ventriculoperitoneal shunt tube, which allowed expansion of the depressed scalp flap and facilitated the subsequent cranioplasty. This study describes two patients who were treated for this problem after severe head trauma. Results: When performing a titanium mesh cranioplasty after a shunt, this new method facilitated the separation of the scalp from the underlying muscle or dura and obliterated the dead space between the titanium mesh and the underlying tissue. Both patients had satisfactory outcomes without complications. Conclusions: This method is easy and safe and it facilitates the cranioplasty, reducing the potential complications, including intracranial haematoma, effusions and infection, and thereby improving the patient outcome.

Shunt implantation in a special sub-group of post-traumatic hydrocephalus—patients have normal intracranial pressure without clinical representations of hydrocephalus

Background: Post-traumatic hydrocephalus (PTH) is a frequent complication secondary to traumatic brain injury (TBI) and controversy remains over whether to perform a shunt placement for patients with normal pressure hydrocephalus when the patient is too injured to display symptoms or has atypical symptoms. Method: A hospital-based retrospective study was performed in patients who developed normal pressure hydrocephalus, without atypical symptoms, from January 2004 to June 2007. Information regarding patients’ demographics, TBI, hydrocephalus and outcome was collected. Results: A total of 31 patients were involved in this study. At the 12-month follow-up, 20 patients (64.5%) showed clear improvement. Among the 10 patients who developed PTH after decompressive craniectomy, cranioplasty was performed after shunt implantation and clinical improvement was observed in nine patients. Additionally, in this series, the patients’ age and the severity of hydrocephalus, assessed by CT imaging before shunt placement, significantly correlated with improvement. Conclusion: Although the effect was not definitively established, many patients in the sub-group of PTH patients described here would benefit from shunt placement, especially when they simultaneously have large cranial defects after surgical decompression and underwent cranioplasties after shunt placement. Additionally, younger patients and those with less severe hydrocephalus before shunt placement may expect a better outcome after shunt placement.

Long noncoding RNA MEG3 mediated angiogenesis after cerebral infarction through regulating p53/NOX4 axis

OBJECTIVE This study aimed to explore the mechanism of lncRNA MEG3 on angiogenesis after cerebral infarction (CI). METHODS The rat brain microvascular endothelial cells (RBMVECs) isolated from rat was used to establish CI model, which were treated with oxygen-glucose deprivation/reoxygenation (OGD/R). The genes mRNA and protein expression levels in RBMVECs were determined by the quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively. The flow cytometry was used to measured cell apoptosis and intracellular reactive oxygen species (ROS) generation. The RBMVECs activities was detected by MTT method. The RNA-immunoprecipitation (RIP) assay was used to detect the interaction between MEG3 and p53, and the relationship between p53 and NOX4 was proved by chromatin co-immunoprecipitation (chip) assay. RESULTS The results showed that OGD or OGD/R increased MEG3 and NOX4 expression, and there was positive correlation between MEG3 and NOX4 expression in RBMVECs. Next, knockdown of MEG3 indicated that inhibition of MEG3 was conducive to protect RBMVECs against OGD/R-induced apoptosis, with decreased NOX4 and p53 expression, further enhanced pro-angiogenic factors (HIF-1α and VEGF) expression, and reduced intracellular ROS generation. And then the RIP and CHIP assay demonstrated that MEG3 could interacted with p53 and regulated its expression, and p53 exerted significant binding in the promoters for NOX4, suggesting that MEG3 regulated NOX4 expression via p53. At last, knockdown of NOX4 indicated that inhibition of NOX4 protected RBMVECs against OGD/R-induced apoptosis, with increased cell viability and pro-angiogenic factors expression, and reduced ROS generation. CONCLUSION LncRNA MEG3 was an important regulator in OGD/R induced-RBMVECs apoptosis and the mechanism of MEG3 on angiogenesis after CI was reduced ROS by p53/NOX4 axis.

Efficacy of large decompressive craniectomy in severe traumatic brain injury.

OBJECTIVE To investigate the role of large decompressive craniectomy (LDC) in the management of severe and very severe traumatic brain injury (TBI) and compare it with routine decompressive craniectomy (RDC). METHODS The clinical data of 263 patients with severe TBI (GCS < or = 8) treated by either LDC or RDC in our department were studied retrospectively in this article. One hundred and thirty-five patients with severe TBI, including 54 patients with very severe TBI (GCS < or = 5), underwent LDC (LDC group). The other 128 patients with severe TBI, including 49 patients with very severe TBI, underwent RDC (RDC group). The treatment outcome and postoperative complications of the two treatment methods were compared and analyzed in a 6-month follow-up period. RESULTS Ninety-six patients (71.7 %) obtained satisfactory treatment outcome in the LDC group, while only 75 cases (58.6 %) obtained satisfactory outcome in the RDC group (P < 0.05). Moreover, the efficacy of LDC in treating very severe TBI was higher than that of RDC (63.0 % vs. 36.7 %, P < 0.01). The chance of reoperation due to refractory intracranial pressure (ICP) in the LDC group was significantly lower than that of the RDC group (P < 0.05), while the incidences of delayed intracranial hematoma and subdural effusion were significantly higher than those of the RDC group ( P < 0.05). CONCLUSIONS LDC is superior to RDC in improving the treatment outcome of severe TBI, especially the very severe ones. LDC can also efficiently reduce the chances of reoperation due to refractory ICP. However, it increases the incidences of delayed intracranial hematoma and contralateral subdural effusion.

Subdural effusion secondary to decompressive craniectomy in patients with severe traumatic brain injury

Dear Editor, Firstly, thanks for the attention on our study. Nowadays, decompressive craniectomy is an important method for the management of patients with severe head trauma, and apparently the prevention and management of complications are crucial parts of this surgical method. Actually, a great part of these complications would be secondary to head trauma or craniotomy as well, including subdural effusion, post-traumatic hydrocephalus, intracranial infection, cerebrospinal fluid leakage, intracranial rehemorrhage, and epilepsy. Subdural effusion is a complication that could be secondary to both head trauma and craniotomy. The incidence rate of subdural effusion in head trauma was between 7 and 12% [3], and that after decompressive craniectomy was between 21 and 50% reportedly [1, 2, 4, 5]. In our series, this rate was 21.3%. We agree on the explanation of the reasons for the high incidence of subdural effusion secondary to decompressive craniectomy from Dr. Cumher Kilincer. However, here we want to emphasize another reason for the development of subdural effusion. We have treated a patient who was transferred to our hospital 2 months after surgical decompression for severe head trauma. The local hospital sent him to our hospital for deterioration of consciousness, and the CT scan disclosed subdural effusion contralateral to the decompressive side (Fig. 1). We reviewed the patient’s medical record, and it was found that though the brain edema was not disclosed from the CT on the late phase of head trauma the treatment of dehydration was still lasted. The excessive dehydration was believed to be an important reason for the development of subdural effusion. After stopping the dehydration, this patient recovered under conservative treatment and the CT approved the resolution of effusion. Such a case may not be the only one, and the development

Buyang Huanwu Decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells.

BackgroundApoptosis of endothelial cells caused by reactive oxygen species plays an important role in ischemia/reperfusion injury after cerebral infarction. Buyang Huanwu Decoction (BYHWD) has been used to treat stroke and stroke-induced disability, however, the mechanism for this treatment remains unknown. In this study, we investigated whether BYHWD can protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced apoptosis and explored the underlying mechanisms.MethodsTo investigate the effect of BYHWD on the apoptosis of HUVECs, we established a H2O2-induced oxidative stress model and detected apoptosis by Hoechst 33342 and propidium iodide staining. JC-1 and DCFH-DA assays,western blotting and electron microscopy were used to examine the mechanism of BYHWD on apoptosis.ResultsPretreatment with BYHWD significantly inhibited H2O2-induced apoptosis and protein caspase-3 expression in a concentration-dependent manner. In addition, BYHWD reduced reactive oxygen species production and promoted endogenous antioxidant defenses. Furthermore, loss of mitochondrial membrane potential and structural disruption of mitochondria were both rescued by BYHWD.ConclusionsBYHWD protects HUVECs from H2O2-induced apoptosis by inhibiting oxidative stress damage and mitochondrial dysfunction. These findings indicate that BYHWD is a promising treatment for cerebral ischemia diseases.

The occurrence of diffuse axonal injury in the brain: associated with the accumulation and clearance of myelin debris

The accumulation of myelin debris may be a major contributor to the inflammatory response after diffuse axonal injury. In this study, we examined the accumulation and clearance of myelin debris in a rat model of diffuse axonal injury. Oil Red O staining was performed on sections from the cerebral cortex, hippocampus and brain stem to identify the myelin debris. Seven days after diffuse axonal injury, many Oil Red O-stained particles were observed in the cerebral cortex, hippocampus and brain stem. In the cerebral cortex and hippocampus, the amount of myelin debris peaked at 14 days after injury, and decreased significantly at 28 days. In the brain stem, the amount of myelin debris peaked at 7 days after injury, and decreased significantly at 14 and 28 days. In the cortex and hippocampus, some myelin debris could still be observed at 28 days after diffuse axonal injury. Our findings suggest that myelin debris may persist in the rat central nervous system after diffuse axonal injury, which would hinder recovery.

Contralateral haematoma secondary to decompressive craniectomy performed for severe head trauma: A descriptive study of 15 cases

Background: Contralateral haematoma is an infrequent but severe complication of decompressive craniectomy for head trauma. Method: A retrospective study was performed of patients developing this complication after decompressive craniectomy for head trauma in the institute. Demographics, mechanism of trauma, time interval between trauma and first operation, time interval between first operation and onset of contralateral haematoma and patients’ outcomes were recorded for further analysis. Results: Fifteen patients developed this complication in the study; most had epidural haematomas, which appeared within the first 12 hours after decompressive craniectomy in 13 patients, including three haematomas that developed during surgical decompression. Contralateral cranial fracture is a major risk factor for this condition. Only one patient recovered to mild disability. All remaining patients had poor outcomes, with Glasgow coma scale scores ≤3, except for one patient who was lost to follow-up. A literature review of similar studies including 36 patients revealed similar characteristics. Conclusion: Contralateral haematoma secondary to surgical decompression in head trauma can lead to a poor outcome. The prompt detection and removal of the haematoma are keys to management and routine recurrent computed tomography is recommended after the first operation.

HSPB1 Enhances SIRT2-Mediated G6PD Activation and Promotes Glioma Cell Proliferation

Heat shock proteins belong to a conserved protein family and are involved in multiple cellular processes. Heat shock protein 27 (Hsp27), also known as heat HSPB1, participates in cellular responses to not only heat shock, but also oxidative or chemical stresses. However, the contribution of HSPB1 to anti-oxidative response remains unclear. Here, we show that HSPB1 activates G6PD in response to oxidative stress or DNA damage. HSPB1 enhances the binding between G6PD and SIRT2, leading to deacetylation and activation of G6PD. Besides, HSPB1 activates G6PD to sustain cellular NADPH and pentose production in glioma cells. High expression of HSPB1 correlates with poor survivalrate of glioma patients. Together, our study uncovers the molecular mechanism by which HSPB1 activates G6PD to protect cells from oxidative and DNA damage stress.