Hyperhomocysteinemia Causes Severe Intraoperative Thrombotic Tendency in Superficial Temporal Artery-middle Cerebral Artery Bypass.

CASE: Two years ago, annual magnetic resonance imaging for unruptured right internal carotid artery aneurysm of a 47-year-old woman detected a cerebral infarct in her right occipital lobe which was unknown etiology and antiplatelet therapy was initiated. She presented with sensory disorder of her left fingers 4 months ago. Infarction in right parieto-occipital cortex and severe stenosis of right middle cerebral artery was revealed. Her laboratory test was normal except remarkably high homocysteine value. Regardless of dual anti-platelet therapy, she suffered from repeated minor stroke and the stenosis was progressing. Therefore, right superficial temporal artery - middle cerebral artery bypass was undertaken. Aspirin and clopidogrel were withdrawn 1 week before the surgery. Two branches were anastomosed with 2 separate frontal M4 branches. Although patency was confirmed immediately after the anastomosis, thrombus formation was revealed after 10 minutes. We needed to perform removal of the thrombus and re-anastomosis twice. Intraoperative administration of aspirin and ozagrel alleviated thrombotic tendency. After surgery, antiplatelet therapy and supplementation with folate and vitamin B were performed. Her postoperative course was uneventful and patency of both anastomoses was confirmed. DISCUSSION: Controversy still exists regarding preoperative antiplatelet therapy before superficial temporal artery-middle cerebral artery bypass, and folates and B6-12 vitamins supplementation for hyperhomocysteinemia. Considering intraoperative thrombo tendency in our case, it is recommended to evaluate the homocysteine level before bypass surgery for intracranial stenosis especially for young patients or patients with unknown etiology. Before bypass surgery of the patient with hyperhomocysteinemia, continuation of perioperative antiplatelet drugs and supplementation with folates and B6-12 vitamins are mandatory.

Indication and limitations of endoscopic extended transsphenoidal surgery for craniopharyngioma.

The transsphenoidal approach has been utilized in intrasellar craniopharyngioma surgeries. However, the advent of endoscopic extended transsphenoidal approach (EETSA) has expanded its indication to suprasellar craniopharyngiomas. We compared the indication and limitations of EETSA to those of unilateral basal interhemispheric approach (UBIHA), which presents similar indications for surgery. We analyzed 30 patients with tumors located below the foramen of Monro and the lateral boundary extending slightly beyond the internal carotid artery (UBIHA: N = 18; EETSA: N = 12). Postoperative magnetic resonance imaging (MRI) revealed gross total resection in 10 patients in the EETSA group (83.3%) and 12 in the UBIHA group (66.7%). Postoperative MRI in the EETSA group revealed residual tumor at the cavernous sinus in one patient, at the prepontine in one; in the UBIHA group, residual tumors were located in the retrochiasmatic area in two patients, infundibulum-hypothalamus in one, on the stalk in one, and in the intrasellar region in two. No intergroup differences were observed in the preservation of pituitary function and postoperative improvement of visual function. The extent of resection was better with EETSA than with UBIHA. EETSA is considered the first-line therapy because the distance between the optic chiasm and the superior border of the pituitary is large; the lateral extension does not go beyond the internal carotid artery; and the tumor does not extend inferiorly beyond the posterior clinoid process. However, in patients showing poorly developed sphenoid sinuses or pituitary stalks anterior to the tumor, surgery is difficult regardless of the selection criteria.

Calreticulin, a molecular chaperone in the endoplasmic reticulum, modulates radiosensitivity of human glioblastoma U251MG cells.

Radiotherapy is the primary and most important adjuvant therapy for malignant gliomas. Although the mechanism of radiation resistance in gliomas has been studied for decades, it is still not clear how the resistance is related with functions of molecular chaperones in the endoplasmic reticulum. Calreticulin (CRT) is a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum. Recently, it was reported that changes in intracellular Ca(2+) homeostasis play a role in the modulation of apoptosis. In the present study, we found that the level of CRT was higher in neuroglioma H4 cells than in glioblastoma cells (U251MG and T98G), and was well correlated with the sensitivity to gamma-irradiation. To examine the role of CRT in the radiosensitivity of malignant gliomas, the CRT gene was introduced into U251MG cells, which express low levels of CRT, and the effect of overexpression of CRT on the radiosensitivity was examined. The cells transfected with the CRT gene exhibited enhanced radiation-induced apoptosis compared with untransfected control cells. In CRT-overexpressing cells, cell survival signaling via Akt was markedly suppressed. Furthermore, the gene expression of protein phosphatase 2Ac alpha (PP2Ac alpha), which is responsible for the dephosphorylation and inactivation of Akt, was up-regulated in CRT-overexpressing cells, and the regulation was dependent on Ca(2+). Thus, overexpression of CRT modulates radiation-induced apoptosis by suppressing Akt signaling through the up-regulation of PP2Ac alpha expression via altered Ca(2+) homeostasis. These results show the novel mechanism by which CRT is involved in the regulation of radiosensitivity and radiation-induced apoptosis in malignant glioma cells.

Vitamin E prevents the neuronal cell death by repressing cyclooxygenase-2 activity.

The accumulation of damage caused by oxidative stress exacerbates cell death in many neurodegenerative diseases. We evaluated the mechanism of neuronal cell death raised by glutamate-induced toxicity, using the immortalized mouse hippocampal cell line HT-22. Our results showed that vitamin E prevented glutamate-induced cell death, accompanied by the decline of cyclooxygenase-2 expression confirmed by reverse transcriptase polymerase chain reaction and immunocytochemistry. Moreover, the neuroprotection was still effective even when vitamin E was supplied after glutamate treatment. The decline of cyclooxygenase-2 activity was also highly correlated with the neural protective effect against glutamate-induced toxicity. These results represent new insights about the timing of vitamin E supplementation after toxic stimulation and one mechanism by which vitamin E could prevent neuronal cell death by controlling cyclooxygenase-2 activity.