Arterial spin labeling of cerebral perfusion territories using a seperate labeling coil

Purpose: To obtain cerebral perfusion territories of the left, the right. and the posterior circulation in humans with high signal-to-noise ratio (SNR) and robust delineation. Materials and Methods: Continuous arterial spin labeling (CASL) was implemented using a dedicated radio frequency (RF) coil. positioned over the neck, to label the major cerebral feeding arteries in humans. Selective labeling was achieved by flow-driven adiabatic fast passage and by tilting the longitudinal labeling gradient about the Y-axis by theta = +/- 60 degrees. Results: Mean cerebral blood flow (CBF) values in gray matter (GM) and white matter (WM) were 74 +/- 13 mL center dot 100 g(-1) center dot minute(-1) and 14 +/- 13 mL center dot 100 g(-1) center dot minute(-1), respectively (N = 14). There were no signal differences between left and right hemispheres when theta = 0 degrees (P > 0.19), indicating efficient labeling of both hemispheres. When theta = +60 degrees, the signal in GM on the left hemisphere, 0.07 +/- 0.06%, was 92% lower than on the right hemisphere. 0.85 +/- 0.30% (P < 1 x 10(-9)). while for theta = -60 degrees, the signal in the right hemisphere. 0.16 +/- 0.13%, was 82% lower than on the contralateral side. 0.89 +/- 0.22% (P < 1 x 10(-10)). Similar attenuations were obtained in WM. Conclusion: Clear delineation of the left and right cerebral perfusion territories was obtained, allowing discrimination of the anterior and posterior circulation in each hemisphere.

Untreated dental caries in children with cerebral palsy in the Brazilian context

Objectives. To assess the prevalence of untreated dental caries in children with cerebral palsy and to assess socio-demographic, behavioural, and clinical covariates. Design. Cross-sectional assessment of 200 children and adolescents with cerebral palsy (2-17 years old) enrolled in a specialized healthcare unit in Sao Paulo, Brazil. The dental examination followed the World Health Organization`s guidelines for oral health surveys; familial caretakers informed on socio-economic status and behaviour; the patient`s medical record informed their clinical status. Results. The proportion of children that presented at least one tooth affected by untreated caries was 49.5%. Poor socio-economic standings and a higher frequency of sugar consumption associated with a worse profile of dental health; different types of cerebral palsy (spastic, tetraparesis) did not. The prevalence of untreated caries was higher than reference values assessed for the overall population of the same age range. Conclusions. The high burden of untreated dental caries on cerebral palsy patients reinforces the importance of the dentist in the interdisciplinary healthcare team attending these children. Factors associated with this outcome are the same for the general population; these findings underscore the necessity of implementing effective caries prevention in this population of cerebral palsy children.

Correlation of the in vitro antifungal drug susceptibility with the in vivo activity of fluconazole in a murine model of cerebral infection caused by Cryptococcus gattii

Forty Cryptococcus gattii strains were submitted to antifungal susceptibility testing with fluconazole, itraconazole, amphotericin B and terbinafine. The minimum inhibitory concentration (MIC) ranges were 0.5-64.0 for fluconazole, < 0.015-0.25 for itraconazole, 0.015-0.5 for amphotericin B and 0.062-2.0 for terbinafine. A bioassay for the quantitation of fluconazole in murine brain tissue was developed. Swiss mice received daily injections of the antifungal, and their brains were withdrawn at different times over the 14-day study period. The drug concentrations varied from 12.98 to 44.60 mu g/mL. This assay was used to evaluate the therapy with fluconazole in a model of infection caused by C. gattii. Swiss mice were infected intracranially and treated with fluconazole for 7, 10 or 14 days. The treatment reduced the fungal burden, but an increase in fungal growth was observed on day 14. The MIC for fluconazole against sequential isolates was 16 mu g/mL, except for the isolates obtained from animals treated for 14 days (MIC = 64 mu g/mL). The quantitation of cytokines revealed a predominance of IFN-gamma and IL-12 in the non-treated group and elevation of IL-4 and IL-10 in the treated group. Our data revealed the possibility of acquired resistance during the antifungal drug therapy.

Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions

7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1(-/-) mice compared with OGG1(+/+) mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 680-692; doi:10.1038/jcbfm.2010.147; published online 25 August 2010

Does the neuromotor abnormality type affect the salivary parameters in individuals with cerebral palsy?

Background: Previous studies reported alterations in salivary flow rate and biochemical parameters of saliva in cerebral palsy (CP) individuals; however, none of these considered the type of neuromotor abnormality among CP individuals, thus it remains unclear whether the different anatomical and extended regions of the brain lesions responsible for the neurological damage in CP might include disruption of the regulatory mechanism of saliva secretion as part of the encephalopathy. The aim of this study was to evaluate salivary flow rate, pH and buffer capacity in saliva of individuals with CP, aged 3-16 years, with spastic neuromotor abnormality type and clinical patterns of involvement. Methods: Sixty-seven individuals with CP spasticity movement disorder, were divided in two groups according to age (3-8- and 9-16-years-old) and compared with 35 sibling volunteers with no neurological damage, divided in two groups according to age (3-8- and 9-16-years-old). Whole saliva was collected under slight suction and pH and buffer capacity were determined using a digital pHmeter. Buffer capacity was measured by titration using 0.01N HCL, and flow rate was calculated in ml/min. Results: In both age groups studied, whole saliva flow rate, pH and buffer capacity were significantly lower in the spastic CP group (P < 0.05). The clinical patterns of involvement did not influence the studied parameters. Conclusion: These findings show that individuals with spastic cerebral palsy present lower salivary flow rate, pH and buffer capacity that can increase the risk of oral disease in this population.