Brain ischemia induces apoptosis in neuronal cells, but the mechanism is not well understood. When wild-type mice were subjected to bilateral common carotid arteries occlusion (BCCAO) for 15 min, apoptosis-associated morphological changes and appearance of TUNEL-positive cells were observed in the striatum and in the hippocampus at 48 h after occlusion. RT-PCR analysis revealed that mRNAs for ER stress-associated proapoptotic factor CHOP and an ER chaperone BiP are markedly induced at 12 h after BCCAO. Immunohistochemical analysis showed that CHOP protein is induced in nuclei of damaged neurons at 24 h after occlusion. In contrast, ischemia-associated apoptotic loss of neurons was decreased in CHOP À/À mice. Primary hippocampal neurons from CHOP À/À mice were more resistant to hypoxiareoxygenation-induced apoptosis than those from wild-type animals. These results indicate that ischemia-induced neuronal cell death is mediated by the ER stress pathway involving CHOP induction.

Apoptosis plays an important role in delayed neuronal cell death after cerebral ischemia. Activation of Akt/protein kinase B has been recently reported to prevent apoptosis in several cell types. In this article the authors examine whether induction of ischemic tolerance resulting from a sublethal ischemic insult requires Akt activation. Sublethal ischemia gradually and persistently stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after reperfusion. After lethal ischemia, phosphorylation of Akt-Ser-473 showed no obvious decrease in preconditioned gerbils but a marked decrease in nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation were correlated with changes in Akt activities, as measured by an in vitro kinase assay. Intracerebral ventricular infusion of wortmannin before preconditioning blocked both the increase in Akt-Ser-473 phosphorylation in a dose-dependent manner and the neuroprotective action of preconditioning. These results suggest that Akt activation is induced by a sublethal ischemic insult in gerbil hippocampus and contributes to neuroprotective ischemic tolerance in CA1 pyramidal neurons.

In adult moyamoya patients, dilatation and abnormal branching of the AChA and/or P-CoM are strong predictors of hemorrhagic events.

Among adult patients with supratentorial GBM, female sex and histopathological characteristics consistent with giant cell GBM may be predictive of a better survival rate, as may traditional factors (that is, younger age, good KPS score, more aggressive resection, and a long progression-free interval).

In transient forebrain ischemia, sodium orthovanadate as well as insulinlike growth factor-1 (IGF-1) rescued cells from delayed neuronal death in the hippocampal CA1 region. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti-phospho-Akt/PKB (Akt) antibody showed that phosphorylation of Akt at serine-473 (Akt-Ser-473) in the CA1 region decreased immediately after reperfusion, and in turn transiently increased 6 hours after reperfusion. The decreased phosphorylation of Akt-Ser-473 was not observed in the CA3 region. The authors then tested effects of intraventricular injection of orthovanadate and IGF-1, which are known to activate Akt. Treatment with orthovanadate or IGF-1 30 minutes before ischemia blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with preventing decreased Akt-Ser-473 phosphorylation in the CA1 region observed immediately after reperfusion. Immunohistochemical studies with the anti-phospho-Akt-Ser-473 antibody also demonstrated that Akt was predominantly in the nucleus and was moderately activated in the cell bodies and dendrites of pyramidal neurons after orthovanadate treatment. The orthovanadate treatment also prevented the decrease in phosphorylation of mitogen-activated protein kinase (MAPK). Pretreatment with combined blockade of phosphatidylinositol 3-kinase and MAPK pathways totally abolished the orthovanadate-induced neuroprotective effect. These results suggest that the activation of both Akt and MAPK activities underlie the neuroprotective effects of orthovanadate on the delayed neuronal death in the CA1 region after transient forebrain ischemia.

No abstract

OBJECTIVE: Because it is difficult to predict the compaction of Guglielmi detachable coils (GDCs) after endovascular surgery for aneurysms, we studied the relationship between the coil packing ratio and compaction. Here, we propose a simple method for the preoperative estimation of coil compaction. Using follow-up angiograms, we studied the timing and degree of coil compaction in small terminal and side-wall aneurysms with narrow necks. METHODS: We studied 62 patients with acute ruptured intracranial aneurysms that were small (<10 mm), had a small neck (<4 mm), and were coil embolized with GDC-10s. The aneurysmal volume was calculated using the equation V = 4/3π(a/2) × (b/2) × (c/2), where a, b, and c are the aneurysmal height, length, and width in millimeters, respectively. The coil volume was calculated using the equation V = π(p/2)2 × l × 10, where p represents the GDC-10 coil diameter (0.25 mm) and l is the coil length. We recorded the maximum prospective coil length, L, as that corresponding with the volume of packed coils occupying 30% of the aneurysmal volume. Therefore, L was calculated as L (cm) = 0.3 × a × b × c, and the coil packing ratio was expressed as packed coil length/L × 100. Angiographic follow-up studies were generally performed at 3 months and 1 and 2 years after endovascular surgery. We considered coil compaction exceeding 2 mm as major compaction and recorded minor compaction when it was less than 2 mm of the empty reappeared space in the embolized aneurysm. Aneurysmal location was recorded as terminal or side wall. RESULTS: Of the 62 patients, 16 (25.8%) manifested angiographic coil compaction (10 minor and 6 major compactions); the mean coil packing ratio was 51.9 ± 13.4%. The mean coil packing ratio in the other 46 patients was 80.5 ± 20.2%, and the difference was statistically significant (P < 0.01). In all 6 patients with major compaction, the mean packing ratio was less than 50% and all underwent re-embolization after a mean of 24.9 ± 1.1 months. The 10 patients with minor compaction were conservatively treated, and the degree of compaction did not change during a mean period of 24 months. We detected 93.8% of the compactions within 12 months of coil placement. The aneurysm was of the terminal type in 5 of the 6 patients with major coil compaction. CONCLUSION: In patients who underwent embolization with GDC-10s of aneurysms that were small and had a small neck, the optimal coil packing ratio could be identified with the formula 0.3 × a × b × c. The probability of coil compaction was significantly higher when the coil packing ratio was less than 50%. To detect coil compaction after embolization, follow-up angiograms must be examined regularly for at least 12 months. To detect major coil compaction in patients with terminal type aneurysms, angiographic follow-up should not be shorter than 24 months.

SummaryIschemic tolerance is well known as a neuroprotective effect of pre-conditioning ischemia against delayed neuronal death, however, the mechanism or mechanisms underlying this effect are not fully understood. We investigated the relationship between CREB and ischemic tolerance in gerbil hippocampal CA1 neurons using CRE decoy oligonucleotide. Sublethal ischemia led to an increase in the level of CREB phosphorylation in CA1 regions while lethal ischemia did not. Experiments with NG108-15 cells showed that adding CRE decoy oligonucleotide to culture media significantly inhibited the cell growth rate. The administration of CRE decoy oligonucleotide into gerbil cerebral ventricle decreased CREB-DNA binding activity to 38% of the control. Pre-treatment with CRE decoy oligonucleotide 24 h before the induction of ischemic tolerance decreased CA1 neuronal cell survival to 21% of the control. The present findings suggest that a CREB-mediated transcription system is necessary for the induction of ischemic tolerance.