L-type amino acid transporter 1 (LAT1) is a Na 1 -independent neutral amino acid transport agency and essential for the transport of large neutral amino acids. LAT1 has been identified as a light chain of the CD98 heterodimer from C6 glioma cells. LAT1 also corresponds to TA1, an oncofetal antigen that is expressed primarily in fetal tissues and cancer cells. We have investigated for the first time, the expression of the transporter in the human primary astrocytic tumor tissue from 60 patients. LAT1 is unique because it requires an additional single membrane spanning protein, the heavy chain of 4F2 cell surface antigen (4F2hc), for its functional expression. 4F2hc expression was also determined by immunohistochemistry. Kaplan-Meier analyses demonstrated that high LAT1 expression correlated with poor survival for the study group as a whole (p < 0.0001) and for those with glioblastoma multiforme in particular (p 5 0.0001). Cox regression analyses demonstrated that LAT1 expression was one of significant predictors of outcome, independent of all other variables. On the basis of these findings, we also investigated the effect of the specific inhibitor to LAT1, 2-aminobicyclo-2 (2,2,1)-heptane-2-carboxylic acid (BCH), on the survival of C6 glioma cells in vitro and in vivo using a rat C6 glioma model. BCH inhibited the growth of C6 glioma cells in vitro and in vivo in a dose-dependent manner. KaplanMeier survival data of rats treated with BCH were significant. These findings suggest that LAT1 could be one of the molecular targets in glioma therapy. ' 2006 Wiley-Liss, Inc.

Anti-HMGB1 mAb may provide a novel and effective therapy for TBI by protecting against BBB disruption and reducing the inflammatory responses induced by HMGB1.

Cross-lingual transfer of word embeddings aims to establish the semantic mappings among words in different languages by learning the transformation functions over the corresponding word embedding spaces. Successfully solving this problem would benefit many downstream tasks such as to translate text classification models from resource-rich languages (e.g. English) to low-resource languages. Supervised methods for this problem rely on the availability of cross-lingual supervision, either using parallel corpora or bilingual lexicons as the labeled data for training, which may not be available for many low resource languages. This paper proposes an unsupervised learning approach that does not require any cross-lingual labeled data. Given two monolingual word embedding spaces for any language pair, our algorithm optimizes the transformation functions in both directions simultaneously based on distributional matching as well as minimizing the backtranslation losses. We use a neural network implementation to calculate the Sinkhorn distance, a well-defined distributional similarity measure, and optimize our objective through back-propagation. Our evaluation on benchmark datasets for bilingual lexicon induction and cross-lingual word similarity prediction shows stronger or competitive performance of the proposed method compared to other stateof-the-art supervised and unsupervised baseline methods over many language pairs.

We studied the fate of Nissl-stained dark neurons (N-DNs) following traumatic brain injury (TBI). N-DNs were investigated in the cerebral neocortex and the hippocampus using a rat lateral fluid percussion injury model. Nissl stain, acid fuchsin stain and immunohistochemistry with phosphorylated extracellular signal-regulated protein kinase (pERK) antibody were used in order to assess posttraumatic neurons. In the neocortex, the number of dead neurons at 24 h postinjury was significantly less than that of the observed N-DNs in the earlier phase. Only a few N-DNs increased their pERK immunoreactivity. On the other hand, in the hippocampus the number of dead neurons was approximately the same number as that of the N-DNs, and most N-DNs showed an increased pERK immunoreactivity. These data suggest that not all N-DNs inevitably die especially in the neocortex after TBI. The fate of N-DNs is thus considered to differ depending on brain subfields.

These findings suggest that xCT is an independent predictive factor in GBMs.

A retrospective analysis of 32 patients with tuberculum sellae meningiomas who underwent surgery via a unilateral pterional approach was performed. A selective extradural anterior clinoidectomy (SEAC) technique was added in 20 patients. All patients had visual dysfunction preoperatively. Macroscopically complete removal with Simpson grade II was performed in 28 patients (87.5%). The postoperative visual function improved in 25 (78.1%), did not change in 3 (9.4%), and worsened in 4 patients (12.5%). The SEAC technique was effective, especially for removal of the tumour extending into the sellae/pituitary stalk (9 patients), the optic canal (4 patients) and hypothalamus (4 patients) with preservation of the visual and endocrinological function. These results were superior to those of surgery without SEAC technique. This technique is therefore recommended for complete resection of the tuberculum sellae meningiomas extending to the surrounding anatomical structures as the SEAC procedure reduces the risk of intraoperative optic nerve injury considerably.

Mitogen-activated protein kinases, which play a crucial role in signal transduction, are activated by phosphorylation in response to a variety of mitogenic signals. In the present study, the authors used Western blot analysis and immunohistochemistry to show that phosphorylated extracellular signal-regulated protein kinase (p-ERK) and c-Jun NH2-terminal kinase (p-JNK), but not p38 mitogen-activated protein kinase, significantly increased in both the neurons and astrocytes after traumatic brain injury in the rat hippocampus. Different immunoreactivities of p-ERK and p-JNK were observed in the pyramidal cell layers and dentate hilar cells immediately after traumatic brain injury. Immunoreactivity for p-JNK was uniformly induced but was only transiently induced throughout all pyramidal cell layers. However, strong immunoreactivity for p-ERK was observed in the dentate hilar cells and the damaged CA3 neurons, along with the appearance of pyknotic morphologic changes. In addition, immunoreactivity for p-ERK was seen in astrocytes surrounding dentate and CA3 pyramidal neurons 6 hours after traumatic brain injury. These findings suggest that ERK and JNK but not p38 cascades may be closely involved in signal transduction in the rat hippocampus after traumatic brain injury.

Background: Patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) presenting with large intracerebral (ICH) or sylvian hematomas (SylH) have poor outcomes due to the mass effect of significant brain stem compression following mass effect. On the other hand, decompressive craniectomy (DC) can reduce morbidity and mortality in critically ill patients with massive ischemic infarction and severe head injury. However, the role of DC in SAH patients is not fully understood. We investigated the outcome of DC in poor-grade SAH presenting with large ICH or SylH. Methods: 110 consecutive patients with poor-grade SAH (Hunt & Kosnik (H&K) grades IV and V, and Fisher group 4) were admitted to our hospital between April 1, 1993, and July 30, 2004. We treated 57 of those who presented with large ICH or SylH using DC. We retrospectively reviewed medical charts, radiological findings, operative notes, and video records. Results: Among the 57 patients (mean age 57.8, male 29, female 28), 25 were classified as H&K grade IV and 32 as grade V. Ruptured aneurysms were located on the internal carotid artery in 11 and the middle cerebral artery in 46 patients. 50 of the aneurysms were small, 5 were medium, and 2 were large. Rerupture was preoperatively confirmed in 13 (22.8%). Hypothermia was applied to 17 (29.8%). The Glasgow Outcome Scale on discharge showed good recovery, moderate recovery, severe disability, vegetative state, and death in 8 (14.0%), 13 (22.8%), 16 (28.1%), 8 (14.0%), and 12 (21.1%), respectively. The outcomes of grade IV patients were favorable and poor in 14 (56.0%) and 10 (40.0%), respectively, and 1 (4.0%) died. Conclusion: Several experimental studies have also indicated that DC significantly improves outcome due to reduced intracranial pressure or increased perfusion pressure. Urgent DC for poor-grade SAH with space-occupying hematoma can lead to survival with good recovery in some patients.