Neuroprotection signaling pathway of nerve growth factor and brain-derived neurotrophic factor against staurosporine induced apoptosis in hippocampal H19-7 cells

Neurotrophins protect neurons against excitotoxicity; however the signaling mechanisms for this protection remain to be fully elucidated. Here we report that activation of the phosphatidyl inositol 3 kinase (PI3K)/Akt pathway is critical for protection of hippocampal cells from staurosporine (STS) induced apoptosis, characterized by nuclear condensation and activation of the caspase cascade. Both nerve growth factor (NGF) and brain-derived growth factor (BDNF) prevent STS-induced apoptotic morphology and caspase-3 activity by upregulating phosphorylation of the tropomyosin receptor kinase (Trk) receptor. Inhibition of Trk receptor by K252a altered the neuroprotective effect of both NGF and BDNF whereas inhibition of the p75 neurotrophin receptor (p75NTR) had no effect. Impairment of the PI3K/Akt pathway or overexpression of dominant negative (DN)-Akt abolished the protective effect of both neurotrophins, while active Akt prevented cell death. Moreover, knockdown of Akt by si-RNA was able to block the survival effect of both NGF and BDNF. Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.

Erratum

No abstract available.

A Comparative Study of Operated and Non-operated Groups in Patients with Hepatic Metastasis from Colorectal Cancer

PURPOSE: The prognosis for patients with liver metastases (LM) from colorectal cancer is significantly influenced by the clinician's decision. Recently, there have been remarkable advances in treatment of LM, so there can be some changes in therapeutic modalities. We performed a comparative study between operated and non-operated groups of patients with LM to analyze the clinical outcome. METHODS: From Feb. 2001 to Feb. 2006, 27 patients with LM underwent a hepatectomy, and 113 patients received non-surgical therapy. thirteen hepatectomized cases among the 27 patients had multiple LM. The outcomes of those 13 patients (Group A) were retrospectively compared to those of the non-operated group (Group B, n=21), which had had potentially resectable LM at the initial diagnosis or after chemotherapy, but didn't undergo hepatic resection. RESULTS: After a median follow-up duration of 31.3 months, the estimated 3-years overall survival (OS) rates were 76.9% and 14.3% in group A and B, respectively (P=0.0001). In the stepwise Cox multivariate regression analysis, factors such as the absence of hepatic resection and a greater diameter of the liver mass independently influenced the poor survival (P=0.005 and P=0.012 respectively). Additionally, two radiologists evaluated the intraoperative ultrasonographic (IOUS) results. IOUS detected new metastatic lesions in 4/13 (30%) patients. There were sub-centimeter metastatic lesions (5~7 mm) and had not been detected in SPIO-enhanced MRI. CONCLUSIONS: Our results compared to palliative chemotherapy suggest that aggressive surgical resection should be performed to increase the survival rate in patients with LM. Additionally, the treatment plan for LM patients should be discussed with the gastroenterololgist, the radiologist, the oncologist, and the surgeon.

The Novel Approach of Multiple Colon Cancer Liver Metastases Treatment

Multiple bilobar liver metastases (MBLM) are the main cause of low resectability in the colon cancer liver metastases. The authors experienced one case of initially non-resectable colon cancer liver metastases. He was curatively and safely treated with a two-stage hepatectomy using the new method of future remnant liver volume growing. A 54-year-old man was referred to our department with the sigmoid colon cancer combined with MBLM, which were checked in two small metastatic lesions in the left lobe and five large sized lesions in the right lobe in the computed tomogram (CT). At first, a laparoscopy-assisted anterior resection was performed. We performed the 1st stage hepatectomy 3 weeks after the colon resection. Intra-operative Ultrasonogram (US) found 9 small superficial metastatic lesions in the left lobe. All that lesions were completely removed by non-anatomical wedge resection. An occlusion balloon catheter was placed in the right portal vein through a small branch of the inferior mesenteric vein at that time. The future remnant liver volume was sufficiently increased 3 weeks after the 1st hepatectomy. A right hepatectomy was safely performed 22 days after the 1st hepatectomy. The patient had received a regional chemotherapy (interleukin2 based immuno-chemotherapy through hepatic artery) for 6 months, then has been receiving a systemic chemotherapy (biweekly Oxaliplatin, leucovorin, plus 5-fluorouracil) without any recurrence evidence.

Capillary Telangiectasia of the Posterior Fossa Presenting with Repeated Cerebellar Hemorrhage

Hemorrhage due to capillary telangiectasia is rare. We report a case of capillary telangiectasia presenting with repeated cerebellar hemorrhage in a 38-year-old male. To our knowledge this is the first case of repeated cerebellar hemorrhage from the capillary telangiectasia. At the first operation, we removed hematoma only, but rebleeding occurred repeatedly in the same area. Finally, we evacuated the recurrent hematoma and vascular mass of capillary telangiectasia at the second operation under surgical microscope. Based on the findings of this case and a review of the literature, we conclude that capillary telangiectasia can be the cause of the massive repeated hemorrhage.

Clinical Study on Risk Factors of Hydrocephalus after Aneurysmal Subarachnoid Hemorrhage

OBJECTIVE: The authors analyzed the incidence, the cause and the prognosis of hydrocephalus following aneurysmal subarachnoid hemorrhage to evaluate the risk factors of hydrocephalus and to provide the proper treatment method for hydrocephalus following aneurysmal subarachnoid hemorrhage. METHODS: The 505 cases of subarachnoid hemorrhage followed by aneurysmal surgery from January 1990 to May 1999, were divided into shunt group and shunt-free group and we were reviewed for the clinical status, Fisher's grade, brain CT findings and prognosis. RESULTS: The incidence of acute hydrocephalus was 37.2% of patients and 18.9% to developed chronic hydrocephalus. Shunt surgery due to chronic hydrocephalus was required in 6.5% of patients. We found following variables were significantly related to shunt-dependent hydrocephalus: high Hunt-Hess and Fisher grade, initial CT findings of intraventricular hemorrahge, posterior circulation aneurysm, preoperative rebleeding, delayed ischemic deficits, and initial high ventricular size index. There were no statistically significant relationships between shunt-dependent hydrocephalus and patient age or sex, timing of operation. The previous hypertension was not related to shunt dependent hydrocephalus. Prognosis in shunt group showed poor result. CONCLUSION: The risk factors of hydrocephalus following aneurysmal subarachnoid hemorrhage are high Hunt-Hess grade, high Fisher's grade, aneurysms of posterior circulations, preoperative aneurysmal rebleeding, delayed ischemic deficits, initial CT findings of intraventricular hemorrahge and initially increased ventricular size. The patients with these factors should the carefully observed and managed accordingly due to poor prognosis related to hydrocephalus requiring shunt operation.

Clinical Analysis of Surgically Treated 134 Cases of Anterior Communicating Artery Aneurysms

This study is a retrospective clinical analysis of 134 cases of anterior communicating artery aneurysms surgically treated in the Department of Neurosurgery, Chungnam National University Hospital from January 1990 to December 1996. The results of analysis were summarized as follows; 1) Peak age incidence was in the sixth decade and male to female ratio was 1: 1.2, showing female predominancy. 2) There was no statistically significant relationship between direction of aneurysm and Fisher's grade, and occurrence of hydrocephalus, and also between the direction, size and shape of aneurysm and preoperative Hunt-Hess grade. 3) There was statistically significant relationship between the shape of aneurysm and angiographic vasospasm; there was high incidence of vasospasm in lobulated and oval shape of aneurysm. But there was no statistically significant relationship between the direction, size of aneurysm and angiographic vasospasm. 4) The correlations between outcome and preoperative Hunt-Hess grade, and occurrence of angiographic vasospasm, and temporary clipping were statistically significant; the outcome was good in cases of no vasospasm, temporay clipping and better preoperative Hunt-Hess grade. 5) The direction, shape and size of aneurysm, existence or not of abnormality in circle of willis, timing of surgery and operative procedure had no statistically significant relationship with outcome. 6) Postoperative complications were vasospasm and infarction(18.7%), brain edema, hydrocephalus, in order of frequency, and the mortality rate was 3%.

Distal Posterior Cerebral Artery Aneurysms: Report of 2 Cases

Two cases of aneurysms in the P3 segment of the posterior cerebral artery are described. These were managed by the subtemporal approach. One giant aneurysm in a 47-year-old male was treated by clipping the afferent artery, and the other small saccular aneurysm in a 41-year-old female was treated by clipping the aneurysmal neck. There were no complications after surgery, and the patients were discharged without neurological deficit. The operative approaches and procedures are also discussed in relation to the anatomy of posterior cerebral artery aneurysms.