Age-related change of neurochemical abnormality in attention-deficit hyperactivity disorder: A meta-analysis

Prevalence and symptoms of attention-deficit hyperactivity disorder (ADHD) change with advancing age. However, neurochemical background of such age-related change is yet to be elucidated. We therefore conducted a meta-analysis of 16 proton magnetic resonance spectroscopy studies comprising 270 individuals with ADHD and 235 controls. Standardized mean differences were calculated and used as an effect size. Sensitivity analyses and meta-regression to explore the effect of age on neurochemical abnormality were performed. A random effects model identified a significantly higher-than-normal N-acetylaspartate (NAA) in the medial prefrontal cortex (mPFC), but no significant differences of other metabolites in that area. No significant difference in metabolite levels was demonstrated in any other region. Sensitivity analysis of children with ADHD revealed significantly higher-than-normal NAA, whereas no significant difference was found in adults with ADHD. Meta-regression revealed significant correlation between advanced age and normal levels of NAA in the mPFC, suggesting that age-dependent abnormality of NAA level in the mPFC is a potential neural basis of age-related change of symptoms of ADHD.     

Change of xanthine dehydrogenase and xanthine oxidase activities in rat brain following complete ischaemia

Abstract

We studied the activities of xanthine dehydrogenase and xanthine oxidase in rat forebrain after complete ischaemia. Complete ischaemia was induced by decapitation after transcardiac infusion with saline. The activities of xanthine dehydrogenase and xanthine oxidase immediately after ischaemia were 93.3 ± 38.7 and 18.8 ± 7.7 ptU/mg proteini, respectively, and at 24 h after ischaemia were 183.5 ± 75.1 and 60.8 ± 15.2 fiU/mg protein, respectively. The ratios of xanthine dehydrogenase/xanthin oxidase immediately and 24 h after ischaemia were 5.04 ± 1.03 and 3.04 ± 0.99, respectively. These data indicate that xanthine dehydrogenase and xanthine oxidase activities were maintained even 24 h after complete ischaemia. Conversion of xanthine dehydrogenase to xanthine oxidase proceeds slowly during complete ischaemia. [Neurol Res 1992; 14: 321-324]     

Comparison of magnetoencephalography,functional MRI,and motor evoked potentials in the localization of the sensory-motor cortex

Abstract

To clarify the topographical relationship between peri-Rolandic lesions and the central sulcus, we carried out presurgical functional mapping by using magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) on 5 patients. The sensory cortex was identified by somatosensory evoked magnetic fields using MEG (magnetic source imaging (MSI)). The motor area of the hand region was identified using f-MRI, during a hand squeezing task. In addition, transcranial magnetic stimulation localized the hand motor area on the scalp, which was mapped onto the MRI. In all cases, the sensory cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions. [Neurol Res 1995; 17: 361-367] cortical vein or the lack of any functional activation in the area of peri-lesional edema. MEPs were also unable to localize the entire motor strip. Therefore, at present, MSI is considered to be the most reliable method to localize peri-Rolandic lesions. [Neurol Res 1995; 17: 361-367]     

Appearance of neural stem cells around the damaged area following traumatic brain injury in aged rats

We have previously reported free radical production after traumatic brain injury (TBI), which induces neural stem cell (NSC) degeneration and death. However, the effects of aging on NSC proliferation around the damaged area following TBI have not been investigated. Therefore, in this study, we used 10-week (young group) and 24-month-old (aged group) rat TBI models to investigate the effects of aging on NSC proliferation around damaged tissue using immunohistochemical and ex vivo techniques. Young and aged rats received TBI. At 1, 3 and 7 days after TBI, immunohistochemical and lipid peroxidation studies were performed. Immunohistochemistry revealed that the number of nestin-positive cells around the damaged area after TBI in the aged group decreased significantly when compared with those in the young group (P < 0.01). However, the number of 8-hydroxy-2′-deoxyguanosine-, 4-hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells and the level of peroxidation around the damaged area after TBI significantly increased in the aged group, compared with those in the young group (P < 0.01). Furthermore, almost all ssDNA-positive cells in young and aged groups co-localized with NeuN and nestin staining. Ex vivo studies revealed that neurospheres, which differentiated into neurons and glia in culture, could only be isolated from injured brain tissue in young and aged groups at 3 days after TBI. These results indicate that, although there were fewer NSCs that have the potential to differentiate into neurons and glia, these NSCs escaped free radical-induced degeneration around the damaged area after TBI in the aged rat brain.     

ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)^H46R rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins—inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1^H46R rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1^H46R rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.     

Serum soluble CD163 levels in patients with influenza-associated encephalopathy

Background: Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin–haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. Methods: We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Results: Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Conclusions: Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE.