Altered expression of K+ -Cl- cotransporters affects fast paired-pulse inhibition during GABA receptor activation in the gerbil hippocampus

K+ -Cl- cotransporter (KCC) plays an important role in maintaining neuronal activity. However, the effect of seizure activity or pharmacological manipulation of GABAergic transmission on KCC expression remains to be clarified. Therefore, the present study was performed to investigate whether seizure activity or GABA receptor agonist treatment changes KCC expression in the gerbil hippocampus. Furthermore, the effect of blockade of KCC on inhibitory transmission in the dentate gyrus was identified following applications of GABA receptor agonists. The distribution of KCC immunoreactivity in the hippocampus was similarly detected between seizure-resistant (SR) and seizure-sensitive (SS) gerbils. Baclofen (a GABAB receptor agonist) treatment markedly increased KCC expression in the gerbil hippocampus. Baclofen treatment significantly reduced paired-pulse inhibition in the dentate gyrus. Furosemide (a KCC inhibitor) treatment amplified the effect of baclofen on paired-pulse responses. In contrast, muscimol (a GABAA receptor agonist) treatment reduced KCC expression. Enhanced paired-pulse inhibition by muscimol treatment was not affected by furosemide treatment. These findings suggest that seizure activity in the gerbil may not affect KCC expression in the hippocampus. In addition, altered KCC immunoreactivity induced by baclofen or muscimol may play an important role in maintaining or regulating inhibitory transmission during GABA receptor activation.     

Ischemia-related changes of glial-derived neurotrophic factor and phosphatidylinositol 3-kinase in the hippocampus: their possible correlation in astrocytes

In the present study, we observed the changes of endogenous expression of glial-cell-line-derived neurotrophic factor (GDNF) and phosphatidylinositol 3-kinase (PI-3 kinase) in the gerbil hippocampus after transient forebrain ischemia and investigated the correlation between GDNF and PI-3 kinase in the ischemic hippocampus. In the sham-operated group, GDNF and PI-3 kinase immunoreactivity was not found in any cells in the hippocampal CA1 region. GDNF, not PI-3 kinase, immunoreactivity was expressed in non-pyramidal cells in the CA1 region at 6 h after ischemic insult. At 12-24 h after ischemia, GDNF and PI-3 kinase immunoreactivity in the CA1 region was similar to that of the sham-operated group. From 2 days after ischemic insult, GDNF- and PI-3-kinase-immunoreactive astrocytes were detected in the CA1 region, and GDNF and PI-3 kinase immunoreactivity in astrocytes was highest in the CA1 region 4 days after ischemic insult. Moreover, at this time point, GDNF and PI-3 kinase were co-localized in some astrocytes. Western blotting showed that ischemia-related changes of GDNF and PI-3 kinase protein levels were similar to the immunohistochemical changes after ischemia. These results suggest that GDNF and PI-3 kinase may be related to delayed neuronal death and that GDNF and PI-3 kinase may be involved in activation of astrocytes.     

Neurocognitive and symptom correlates of daily problem-solving skills in schizophrenia

Functional outcome for individuals with schizophrenia has been associated with cognitive impairment. Deficits in attention, memory, speed of information processing and problem-solving skills affect independent functioning, vocational performance, and interpersonal functioning. This study investigated the relationship between neurocognitive functioning, clinical symptoms and daily problem-solving skills in seriously and persistently ill persons. Thirty-eight inpatients and outpatients were administered a neurocognitive battery for attention, working memory, processing speed, perceptual organization, and executive functioning; and semi-structured clinical interviews using the BPRS and SANS. Estimates of daily problem-solving skills were obtained using the relevant factor subscale from the Independent Living Scales (ILS-PB). Daily problem-solving skills were significantly correlated with negative symptoms, processing speed, verbal memory, and working memory scores. A regression model using an enter method suggests that working memory and negative symptoms are significant predictors of daily problem-solving skills and account for 73.2% of the variance. Further analyses demonstrate that daily problem-solving skills and negative symptoms were significantly different for inpatients and outpatients and significantly correlated with community status. The findings suggest the ILS-PB has utility as a proxy measure for assessing real-world functioning in schizophrenia.     

Bilateral movement training and stroke rehabilitation: a systematic review and meta-analysis

OBJECTIVE AND DESIGN: Bilateral movement training is being increasingly used as a post-stroke motor rehabilitation protocol. The contemporary emphasis on evidence-based medicine warrants a prospective meta-analysis to determine the overall effectiveness of rehabilitating with bilateral movements. METHODS: After searching reference lists of bilateral motor recovery articles as well as PubMed and Cochrane databases, 11 stroke rehabilitation studies qualified for this systematic review. An essential requirement for inclusion was that the bilateral training protocols involved either functional tasks or repetitive arm movements. Each study had one of three common arm and hand functional outcome measures: Fugl-Meyer, Box and Block, and kinematic performance. RESULTS: The fixed effects model primary meta-analysis revealed an overall effect size (ES=0.732, S.D.=0.13). These findings indicate that bilateral movement training was beneficial for improving motor recovery post-stroke. Moreover, a fail-safe analysis indicated that 48 null effects would be necessary to lower the mean effect size to an insignificant level. CONCLUSION: These meta-analysis findings indicate that bilateral movements alone or in combination with auxiliary sensory feedback are effective stroke rehabilitation protocols during the sub-acute and chronic phases of recovery.     

Staurosporin induces neurite outgrowth through ROS generation in HN33 hippocampal cell lines

Summary. Staurosporin, a specific inhibitor of PKC, is widely used in studies of signal transduction pathways. Previous studies have shown that staurosporin induces neurite outgrowth, but the underlying mechanisms remain unclear. Here we report that staurosporin induces neurite outgrowth in HN33 hippocampal cells. Two other PKC inhibitors, Go 6976 (specific for α- and β-isoforms) and rotterlin (a selective inhibitor of PKC δ), have no neuritogenic effect. In addition, staurosporin specifically increases ROS generation. NAC, which inhibits the generation of ROS, suppresses the staurosporin-induced neurite outgrowth in HN33 cells. Further, H₂O₂ causes neurite outgrowth. Taken together, these results confirm a neuritogenic effect of staurosporin and point to ROS as the signal mediator of staurosporin-induced neurite outgrowth in HN33 hippocampal cells. Theme: Development and regeneration Topic: Neurotrophic factors: receptors and cellular mechanisms     

Levodopa availability improves with progression of Parkinson’s disease

Background Previous pharmacokinetic trials with standard levodopa formulations showed a different behaviour of levodopa degradation in plasma of patients with Parkinson’s disease (PD) in various stages. Objectives To investigate associations between levodopa plasma levels in relation to the scored intensity of PD. Subjects and Methods We administered water soluble 100 mg levodopa and 25 mg benserazide to 50 PD patients, taken off medication for at least 12 hours, and assessed the levodopa plasma concentrations during an 180 minutes period under standardised conditions. Results The computed area under the curve (AUC) values of levodopa plasma levels were significant higher in advanced PD patients. PD rating scores significantly correlated to the AUC outcomes and the maximum levodopa plasma concentration. Conclusions Levodopa availability improves with progression of PD. This may result from deteriorated peripheral activity of levodopa metabolising enzymes or an increasing enteric dysfunction with subsequent better duodenal levodopa absorption or both. Received in revised form: 12 February 2005     

Biogenetic temperament and character and attention deficit hyperactivity disorder in Korean children

BACKGROUND: The objective of this study was to evaluate the relationship between symptoms of attention deficit hyperactivity disorder (ADHD) and biogenetic temperament, as assessed by the Junior Temperament and Character Inventory (JTCI) in Korean elementary school children. SAMPLING AND METHODS: Five hundred and sixteen elementary school students (254 boys and 262 girls; age range 9-14 years, mean age 11.0 +/- 1.0 years) were studied. The Junior Temperament and Character Inventory, both the self-rating and parent rating scales, the DuPaul ADHD rating scale (ARS-IV) for parents and teachers and the Child Behavior Checklist have been completed by study subjects. Children with high ARS-IV scores (the upper 10th percentile, n = 52) were defined to have ADHD. Fifty-two age- and sex-matched non-ADHD control subjects were selected randomly from a pool of 464 subjects. RESULTS: Inattention and hyperactivity/impulsivity symptoms correlated positively with Novelty Seeking in both children and parent ratings. These symptoms correlated negatively with Persistence, Self-Directedness and Cooperativeness. Novelty Seeking also had significant correlations with attention problems, delinquent behavior, aggressive behavior, externalizing problems and social problems in the Child Behavior Checklist. The ADHD group (n = 52) had higher scores of Novelty Seeking and lower scores of Self-Directedness and Cooperativeness, compared with the control group. CONCLUSIONS: There were significant correlations between ADHD symptoms and Novelty Seeking. Current findings suggest that Novelty Seeking and ADHD share biogenetic backgrounds.     

Detecting axon damage in spinal cord from a mouse model of multiple sclerosis

In the current study, the feasibility and reproducibility of in vivo diffusion tensor imaging (DTI) of the spinal cord in normal mice are illustrated followed by its application to mice with experimental allergic encephalomyelitis (EAE) to detect and differentiate axon and myelin damage. Axial diffusivity, describing water movement along the axonal fiber tract, in all regions of spinal cord white matter from EAE-affected C57BL/6 mice was significantly decreased compared to normal mice, whereas there was no statistically significant change in radial diffusivity, describing water movement across the fiber tract. Furthermore, a direct comparison between DTI and histology from a single mouse demonstrated a decrease in axial diffusivity that was supported by widespread staining of antibody against beta-amyloid precursor protein. Regionally elevated radial diffusivity corresponded with locally diminished Luxol fast blue staining in the same tissue from the EAE mouse cord. Our findings suggest that axonal damage is more widespread than myelin damage in the spinal cord white matter of mice with EAE and that in vivo DTI may provide a sensitive and specific measure of white matter injury.     

Two cases of spontaneous middle cerebral arterial dissection causing ischemic stroke

Spontaneous middle cerebral arterial dissection (MCAD) is a rare cause of ischemic stroke. We report two cases of isolated spontaneous MCAD causing ischemic stroke. MCAD should be considered when a young patient has a middle cerebral artery territory infarct with stenosis at the origin of the middle cerebral artery. We discuss noninvasive radiological techniques for the diagnosis of MCAD.     

Ketogenic diet for treatment of infantile spasms

This study sought to evaluate the efficacy, tolerability, and safety of a ketogenic diet (KD) in the treatment of infantile spasms (IS), incorporating a revised protocol based on our previous experience with KD. We undertook a retrospective analysis of 43 children who suffered from catastrophic IS and tried KD from June 1995 to May 2004 in two Korean epilepsy centers. Outcome measures included seizure frequency, electroencephalograms (EEGs), adverse reactions, and neurological development. Overall, the diet achieved the seizure-free state in 53.5% (23/43) of patients and a greater than 90% reduction of seizure frequency in 62.8% (27/43) of patients. The seizure outcomes were highly concordant with improvements in EEG findings and development. In addition, KD could be maintained more safely and more comfortably because of our revised protocol that included an initial non-fasting diet, a short-term trial of 8 months, a more protein-rich diet with a lipid to non-lipid ratio of 3:1, and liquid ketogenic milk. Most complications were transient and KD was well tolerated in most cases. KD can be an effective alternative therapy for catastrophic IS, and additional benefits may be derived from constant revision of the diet in the future.