Background and Purpose-Increased activation of excitatory amino acid (EAA) receptors is considered a major cause of neuronal damage. Possible sources and mechanisms of ischemia-induced EAA release were investigated pharmacologically with microdialysis probes placed bilaterally in rat striatum. Methods-Forebrain ischemia was induced by bilateral carotid artery occlusion and controlled hypotension in halothaneanesthetized rats. During 30 minutes of ischemia, microdialysate concentrations of glutamate and aspartate were measured in the presence of a nontransportable blocker of the astrocytic glutamate transporter GLT-1, dihydrokinate (DHK), or an anion channel blocker, 4,4Ј-dinitrostilben-2,2Ј-disulfonic acid (DNDS), administered separately or together through the dialysis probe. Results-In control striata during ischemia, glutamate and aspartate concentrations increased 44Ϯ13 (meanϮSEM) times and 19Ϯ5 times baseline, respectively, and returned to baseline values on reperfusion. DHK (1 mmol/L in perfusate; nϭ8) significantly attenuated EAA increases compared with control (glutamate peak, 9.6Ϯ1.7 versus control, 15.4Ϯ2.6 pmol/L). EAA levels were similarly decreased by 10 mmol/L DHK. DNDS (1 mmol/L; nϭ5) also suppressed EAA peak increases (glutamate peak, 5.8Ϯ1.1 versus control, 10.1Ϯ0.7 pmol/L). At a higher concentration, DNDS (10 mmol/L; nϭ7) further reduced glutamate and aspartate release and also inhibited ischemia-induced taurine release.

Inhibitors of cell-swelling-activated anion channels, including the antiestrogenic compound tamoxifen (TAM), have been shown to attenuate the increase in excitatory amino acids (EAA) during ischemia. Since TAM enters the CNS we tested whether it provides protection from damage due to reversible middle cerebral artery occlusion (rMCAo) in rats. TAM (5 mg/kg, i.v.) infused 25 min before ischemia, potently reduced the total volume of the infarct from 328 +/- 34 mm3 to 41 +/- 21 mm3, a reduction of 87%, as measured by TTC staining. It was equally effective when infused starting at 1 h after reperfusion, i.e. 3 h after initiation of rMCAo. Protection of neurons was also found histologically. TAM had no effect on CBF as measured by hydrogen clearance. This appears to be the first report of a marked neuroprotective effect of TAM. Further studies are needed to determine whether its effects are due to inhibition of EAA release and/or other potential neuroprotective sites of action.

This case illustrates a rare complication of an unruptured saccular aneurysm with neuroimaging and pathological correlation. Morphological and hemodynamic factors that may have precipitated aneurysm thrombosis are discussed with reference to experimental models.

Background and Purpose-The objective of this study was to assess the relationship between each of 2 provider volume measures for carotid endarterectomies (CEs) (annual hospital volume and annual surgeon volume) and in-hospital mortality. New York's Statewide Planning and Research (SPARCS) administrative database was used to identify all 28 207 patients for whom carotid endarterectomy was the principal procedure performed in New York State hospitals between January 1, 1990, and December 31, 1995. Methods-A statistical model was developed to predict in-hospital mortality using age, admission status, and several conditions found to be associated with higher-than-average mortality. This model was then used to calculate risk-adjusted mortality rates for various intersections of hospital and surgeon volume ranges. Results-Risk-adjusted in-hospital mortality ranged from 1.96% (95%confidence interval, 1.47 to 2.57) for patients having surgeons with annual CE volumes of Ͻ5 in hospitals with annual CE volumes of Յ100 to 0.94% (95% confidence interval, 0.73 to 1.19) for patients having surgeons with annual volumes of Ն5 in hospitals with annual CE volumes of Ͼ100. These 2 rates were statistically different. Conclusions-We conclude that the in-hospital mortality rates for carotid endarterectomies performed by surgeons with extremely low annual volumes (Ͻ5) and for hospitals with low volumes (Յ100) are significantly higher than the in-hospital rates of higher-volume surgeons and hospitals, even after taking preprocedural patient severity of illness into account. (Stroke. 1998;29:2292-2297.)

Subarachnoid hemorrhage (SAH) following cerebral aneurysm rupture is associated with high rates of morbidity and mortality. Surviving SAH patients often suffer from neurological impairment, yet little is currently known regarding the influence of subarachnoid blood on brain parenchyma. The objective of the present study was to examine the impact of subarachnoid blood on glial cells using a rabbit SAH model. The astrocyte-specific proteins, glial fibrillary acidic protein (GFAP) and S100B, were up-regulated in brainstem from SAH model rabbits, consistent with the development of reactive astrogliosis. In addition to reactive astrogliosis, cytosolic expression of the pro-inflammatory cytokine, high-mobility group box 1 protein (HMGB1) was increased in brain from SAH animals. We found that greater than 90% of cells expressing cytosolic HMGB1 immunostained positively for Iba1, a specific marker for microglia and macrophages. Further, the number of Iba1-positive cells was similar in brain from control and SAH animals, suggesting the majority of these cells were likely resident microglial cells rather than infiltrating macrophages. These observations demonstrate SAH impacts brain parenchyma by

Background and Purpose Preischemic spontaneous locomotor activity was distinguished in this laboratory as a factor influencing outcome after 15 and 20 minutes of forebrain ischemia in gerbils. Histological investigations were carried out to analyze potential relations between postischemic survival and a reduction of cerebral damage by spontaneous locomotor activity.Methods Male Mongolian gerbils were divided into two groups, one with access to running wheels ("runners") and one kept in conventional cages ("nonrunners") for 2 weeks preceding forebrain ischemia of 15 or 20 minutes. A total of 99 gerbils were divided in subgroups and were allowed to recover for 2 weeks for assessment of survival. Other subgroups (n=7 to 9) were killed at day 4 for quantitative histology of selectively vulnerable areas such as hippocampus, cortex, striatum, and thalamus.Results Two weeks after 15-minute ischemia, 44% of nonrunners had survived compared with 90% of runners (P<.01).

Object The authors describe the artificial neural network (ANN) as an innovative and powerful modeling tool that can be increasingly applied to develop predictive models in neurosurgery. They aimed to demonstrate the utility of an ANN in predicting survival following traumatic brain injury and compare its predictive ability with that of regression models and clinicians. Methods The authors designed an ANN to predict in-hospital survival following traumatic brain injury. The model was generated with 11 clinical inputs and a single output. Using a subset of the National Trauma Database, the authors “trained” the model to predict outcome by providing the model with patients for whom 11 clinical inputs were paired with known outcomes, which allowed the ANN to “learn” the relevant relationships that predict outcome. The model was tested against actual outcomes in a novel subset of 100 patients derived from the same database. For comparison with traditional forms of modeling, 2 regression models were developed using the same training set and were evaluated on the same testing set. Lastly, the authors used the same 100-patient testing set to evaluate 5 neurosurgery residents and 4 neurosurgery staff physicians on their ability to predict survival on the basis of the same 11 data points that were provided to the ANN. The ANN was compared with the clinicians and the regression models in terms of accuracy, sensitivity, specificity, and discrimination. Results Compared with regression models, the ANN was more accurate (p < 0.001), more sensitive (p < 0.001), as specific (p = 0.260), and more discriminating (p < 0.001). There was no difference between the neurosurgery residents and staff physicians, and all clinicians were pooled to compare with the 5 best neural networks. The ANNs were more accurate (p < 0.0001), more sensitive (p < 0.0001), as specific (p = 0.743), and more discriminating (p < 0.0001) than the clinicians. Conclusions When given the same limited clinical information, the ANN significantly outperformed regression models and clinicians on multiple performance measures. While this paradigm certainly does not adequately reflect a real clinical scenario, this form of modeling could ultimately serve as a useful clinical decision support tool. As the model evolves to include more complex clinical variables, the performance gap over clinicians and logistic regression models will persist or, ideally, further increase.

Background and Purpose-Local Ca 2ϩ release events (Ca 2ϩ sparks) caused by the opening of ryanodine-sensitive Ca