Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess ...the prognostic value of different circulating LP initiators in acute stroke.
Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS).
Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 μg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 μg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 μg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 μg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11-4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90-0.99, p = 0.0001).
The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome.
Highlights • The various stages of the use of type I interferon in multiple sclerosis were reviewed. • We focused on the possible effects of the treatment on the supposed viral etiologic factors that ...have been associated to multiple sclerosis. • An analysis was performed to compare multiple sclerosis-associated genes and components of the interferon-beta pathway.
The question of whether nicotine, the neuroactive compound of tobacco, is addictive has been open to considerable scientific and public discussion. Although it can serve as a positive reinforcer in ...several animal species, including man, nicotine is thought to be a weak reinforcer in comparison with addictive drugs such as cocaine and heroin, and has been argued to be habit forming but not addictive. Here we report that intravenous nicotine in the rat, at doses known to maintain self-administration, stimulates local energy metabolism, as measured by 2-deoxyglucose autoradiography, and dopamine transmission, as estimated by brain microdialysis, in the shell of the nucleus accumbens. These neurochemical and metabolic effects are qualitatively similar to those of other drugs, such as cocaine, amphetamine and morphine, which have strong addictive properties. Our results provide functional and neurochemical evidence that there are specific neurobiological commonalities between nicotine and addictive drugs.
Epilepsy often follows a focal insult, and develops with a time delay so to reveal a complex cascade of events. Both clinical and experimental findings suggest that the initial insult triggers a ...self-promoted pathological process, currently named epileptogenesis. An early phase reflects the complex response of the nervous system to the insult, which includes pro-injury and pro-repair mechanisms. Successively, the sprouting and probably neurogenesis and gliosis set up the stage for the onset of spontaneous seizures. Thus, local changes in excitability would cause a functional change within a network, and the altered circuitry would favor the seizures. A latent or clinically silent period, as long as years, may precede epilepsy. In spite of the substantial knowledge on the biochemical and morphological changes associated with epileptogenesis, the mechanisms supposedly underlying the process are still uncertain. The uncertainty refers mostly to the silent period, a stage in which most, if not all, the receptor and ion changes are supposedly settled. It is tempting to explore the nature of the factors promoting the epileptogenesis within the notional field of neurodegeneration. Specifically, several observations converge to support the hypothesis that a prion-like mechanism promotes the “maturation” process underlying epileptogenesis. The mechanism, consistently with data from different neurodegenerative diseases, is predictably associated with deposition of self-aggregating misfolded proteins and changes of the ubiquitin proteasome and autophagy-lysosome pathways.
Patients suffering from Alzheimer’s disease, Parkinson disease with dementia, and diffuse cerebrovascular dementia show different features of cortical sources of resting state electroencephalographic ...(EEG) rhythms (Babiloni et al., 2004, 2011). Here, we tested the hypothesis that stroke patients are characterized by peculiar abnormalities of these rhythms. Resting state eyes-closed EEG data were recorded in 29 acute stroke, 29 Alzheimer’s disease, 29 mild cognitive impairment patients, and 29 cognitively intact elderly subjects. Stroke patients were age matched with the other groups, they showed a mild cognitive decline. EEG recordings were performed from the 20th to 30th days from the first ischemic or hemorrhagic acute event. LORETA was used for source estimation. Compared to the other groups, the stroke patients were characterized by a greater power of widespread cortical sources of delta (1–4 Hz) and theta (4–8 Hz) rhythms ( p < 0.05). Abnormal cortical sources of delta and theta rhythms reflect the effects of stroke on cortical neural synchronization. The present study motivates future research evaluating the clinical value of delta sources for the prediction of the patients’ recovery and possible cognitive symptoms.
To investigate, in a group of subjects with cognitive impairment, the relationship between anosognosia, in each dimension of insight, and neuropsychological domains.
Two hundred and seventy-one ...subjects affected by cognitive impairment were consecutively enrolled. Anosognosia was evaluated by means of the Clinical Insight Rating Scale (CIRS). The general level of cognitive impairment was evaluated by means of the Mini-Mental State Examination, while 8 cognitive domains were examined by means of neuropsychological tests.
The number of subjects with anosognosia evaluated by means of the CIRS total score as well as those with anosognosia divided according to the reason for visit was higher in moderately cognitively impaired subjects than in mildly cognitively impaired subjects (p < 0.001). A relationship between anosognosia and neuropsychological scores was only found in mild cognitive impairment, with subjects with anosognosia displaying significantly lower Raven's Colored Progressive Matrices Test and Rey Auditory Verbal Learning Test-delayed recall scores than subjects without anosognosia.
Our study suggests that the relationship between the severity of cognitive deficits and anosognosia in subjects with cognitive impairment is partial and depends on the specific domain of unawareness. Furthermore, in the early phase of cognitive impairment, the presence of specific cognitive deficits suggests that the nature of anosognosia is domain-specific.
The mGlu2/3 receptor agonists 4-carboxy-3-hydroxyphenylglycine (4C3HPG) and LY379268 attenuated NMDA toxicity in primary cultures containing both neurons and astrocytes. Neuroprotection was abrogated ...by PD98059 and LY294002, which inhibit the mitogen activated protein kinase (MAPK) and the phosphatidylinositol-3-kinase (PI-3-K) pathways, respectively. Cultured astrocytes lost the ability to produce transforming growth factor-beta1 (TGF-beta1) in response to mGlu2/3 receptor agonists when co-incubated with PD98059 or LY294002. As a result, the glial medium was no longer protective against NMDA toxicity. Activation of the MAPK and PI-3-K pathways in cultured astrocytes treated with 4C3HPG or LY379268 was directly demonstrated by an increase in the phosphorylated forms of ERK-1/2 and Akt. Similarly to that observed in the culture, intracerebral or systemic injections of mGlu2/3 receptor agonists enhanced TGF-beta1 formation in the rat or mouse caudate nucleus, and this effect was reduced by PD98059. PD98059 also reduced the ability of LY379268 to protect striatal neurons against NMDA toxicity. These results suggest that activation of glial mGlu2/3 receptors induces neuroprotection through the activation of the MAPK and PI-3-K pathways leading to the induction of TGF-beta.
Abstract The aim of this retrospective exploratory study was that resting state eyes-closed electroencephalographic (rsEEG) rhythms might reflect brain arousal in patients with dementia due to ...Alzheimer’s disease (ADD), Parkinson’s disease (PDD), and Lewy body (DLB). Clinical and rsEEG data of 42 ADD, 42 PDD, 34 DLB, and 40 healthy elderly (Nold) subjects were available in an international archive. Demography, education, and Mini Mental State Evaluation score were not different between the patient groups. Individual alpha frequency peak (IAF) determined the delta, theta, alpha1, alpha2, and alpha3 frequency bands. Fixed beta1, beta2, and gamma bands were also considered. rsEEG cortical sources were estimated by means of the exact low-resolution brain electromagnetic source tomography and were then classified across individuals, on the basis of the receiver operating characteristic curves. Compared to Nold, IAF showed marked slowing in PDD and DLB and moderate slowing in ADD. Furthermore, all patient groups showed lower posterior alpha 2 source activities. This effect was dramatic in ADD, marked in DLB, and moderate in PDD. These groups also showed higher occipital delta source activities, but this effect was dramatic in PDD, marked in DLB, and moderate in ADD. The posterior delta and alpha sources allowed good classification accuracy (approximately 0.85-0.90) between the Nold subjects and patients, and between ADD and PDD patients. In quiet wakefulness, delta and alpha sources unveiled different spatial and frequency features of the cortical neural synchronization underpinning brain arousal in ADD, PDD, and DLB patients. Future prospective cross-validation studies should test these rsEEG markers for clinical applications and drug discovery.
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