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NITRIC oxide (NO) and adenosine are involved in coincident CNS functions, including long-term potentiation, neuronal protection, neurotoxicity and cerebral blood flow. We tested the hypothesis that glia may act as a cellular link between the two, through adenosine-induced NO release from astrocytes. A direct NO measuring system was used, allowing the kinetics of NO release to be measured. Our results show that adenosine, acting through purinoceptors, causes NO release from cultured cortical astrocytes. Mobilization of calcium from intracellular stores rather than influx is involved in the adenosine-induced activation of NO synthase. These results demonstrate a possible interaction between adenosine and NO in cerebrovascular physiology and neurotoxicity.

The outcome following mild traumatic brain injury (TBI) is controversial. We addressed this topic in a study of neurobehavioural and 'real-world' functioning among 53 children with mild TBI and their matched controls, using statistical methods recently developed for multiple comparisons. Because the study involved calculation of 414 p-values, four methods of adjustment for multiple comparisons, including the Bonferroni method, were used to avoid 'false-positive' statistical significance. The additional three methods allowed greater insight into the data than provided by the standard Bonferroni adjustment. Results showed that at initial testing, three areas of 'real-world' functioning (eating, domestic and home/community living skills) had weak but statistically significant associations with mild injury. No other specific areas of neurobehavioural or 'real-world' functioning had plausible associations with the injury either initially, at 1 year, or when changes over the year were considered. However, the adjustment for multiple comparisons provided additional results. There were statistically significant associations of the injury with the entire domain of neurobehavioural variables both initially and at 1 year. These results suggest that the injury affects a spectrum of neurobehavioural skills weakly, rather than a single area substantially. The gain from using multiple comparison methods is discussed.

The utility of an experimental animal model is dependent on its ability to simulate the actual clinical situation. With a stereotaxic injection procedure, the susceptibility of rat brain to the spectrum of organisms commonly associated with human brain abscess was determined. Two strains of Escherichia coli were more infective than Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes. Even between the E. coli strains it was possible to document significant differences in degree of infectivity. The E. coli strain with the K-1 capsular polysaccharide was significantly more infective than the E. coli strain without the capsular polysaccharide. The brain was also susceptible to Candida albicans, but at a level higher than any of the aerobic bacteria examined. Brain infection could not be created when microaerophilic or obligately anaerobic organisms alone were injected.

Summary Three hundred and sixty-four patients who suffered a subarachnoid haemorrhage from an aneurysm at either the anterior (ACA) or posterior (PCA) communicating artery location and who were not surgically treated have been followed for up to 21 years in order to study the late morbidity and mortality. For the 213 patients surviving to six months or longer : (1) little improvement in morbidity was noted during the many years of subsequent follow-up; (2) in general, ACA patients fared better than PCA patients; (3) the neurological state on original admission was strongly correlated with the degree of morbidity; (4) other factors measured at the time of original haemorrhage which adversely affected morbidity included the level of blood pressure or the presence of clot or spasm ; (5) rebleeding occurs on the average of 3.5% per year during the first decade; (6) the mortality associated with a late rebleed is 67%; (7) if deaths from late haemorrhage are excluded, cardiovascular causes account for the majority of subsequent deaths ; and (8) the risk of dying from all causes is increased when compared to a population matched by age and sex.

The endothelium plays an important role in the modulation of vascular tone and blood cell activation. Extensive work has demonstrated that the release of endothelium-derived relaxing factor (EDRF) from the endothelium is evoked by a number of physical and chemical stimuli requiring Ca2+. Because endothelial cells do not express voltage-dependent Ca2+ channels, Ca2+ influxes following receptor activation may be facilitated by cell hyperpolarizations mediated by the activation of K+ conductances. There has been recent interest in the role of ATP-sensitive K+ channels (KATP) suggesting that KATP may play a role in the regulation of blood flow. We have investigated the electrophysiological properties of an ATP-sensitive K+ conductance in whole cell and membrane patches from rat aorta and brain microvascular endothelial cells. Whole cell as well as single-channel currents were increased by either intracellular dialysis of ATP or application of glucose-free/NaCN (2 mM) solutions. Both currents were reversibly blocked by glibenclamide (1-100 microM). The KATP channel opener pinacidil (30 microM) caused activation of an outward current in the presence of physiological intracellular ATP concentrations. In inside-out patches, 10 microM-1 mM ATP invariably caused a dramatic decrease in channel activity. We conclude that both rat aorta and brain microvascular endothelial cells express KATP channels. KATP may play a role in the regulation of endothelial cell resting potential during impaired energy supply and therefore modulate EDRF release and thus cerebral blood flow.

The occurrence and importance of secondary bacteremia in the pathogenesis of and response to therapy in meningitis is uncertain. Streptococcus pneumoniae type III was injected into the cerebrospinal fluid of the cisterna magna in anesthetized, curarized dogs, and sequential simultaneous samples were obtained from the superior sagittal sinus, cisterna magna, and peripheral blood. The results show that: (i) bacteria are rapidly transported from the cerebrospinal fluid to blood but only after active multiplication within the cerebrospinal fluid, and (ii) entrance into the blood from the cerebrospinal fluid occurs before the height of the febrile response or cerebrospinal fluid pleocytosis.

To examine the neuropsychological side effects of valproate (VPA) given to prevent post-traumatic seizures.

No abstract available.

No abstract available.

Recent reports have indicated that antibiotic therapy alone may be successful in resolving brain abscesses. We utilized an animal model of brain abscess to evaluate the efficacy of penicillin with and without chloramphenicol in preventing the development of brain abscess. When penicillin therapy was initiated at the time of bacterial contamination and continued for four days, the bacteria were eliminated. When therapy was delayed for 24 hr, the number of bacteria in brain tissue samples was significantly reduced, but all samples still contained bacteria. When therapy was delayed for 48 hr, there was no therapeutic benefit. Addition of chloramphenicol to each of these regimens did not significantly alter the results. Extending the duration of therapy to eight days provided no improvement over the results obtained after four days.