HMGB‐1, TLR4, IL‐1R1, TNF‐α, and IL‐1β: novel epilepsy markers?

Aim: The purpose of this study was to compare HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels in patients with mild and severe epilepsy with those in a healthy control group. Methods: Children aged 4–17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB‐1, TLR4, IL‐1R1, TNF‐α and IL‐1β levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. Results: HMGB‐1, TLR4, TNF‐α, and IL‐1β levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL‐1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). Conclusion: In this first report to identity a possible correlation between HMGB‐1, TLR4, IL‐1β, IL‐1R1, and TNF‐α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug‐refractory epilepsy.     

Self‐reported utilization of mental health services in the adult German population – evidence for unmet needs? Results of the DEGS1‐Mental Health Module (DEGS1‐MH)

This paper provides up‐to‐date data on service use for mental health problems and disorders among adults aged 18‐79 years in Germany derived from the Mental Health Module of the German Health Interview and Examination Survey for Adults (DEGS1‐MH; N=4483). Data are based exclusively on self‐report. Respondents were examined by clinically trained interviewers with a modified version of the Composite International Diagnostic Interview DIA‐X/M‐CIDI to assess diagnoses according to the criteria of DSM‐IV‐TR. Service use, i.e. contact to mental health care services, due to mental health problems was assessed for the past 12 months and lifetime, by type of sector and type of institution. Among respondents with a 12‐month diagnosis of a mental disorder, 23.5% of the women and 11.6% of the men reported any service use in the past 12 months. Service use depends on type of diagnosis, comorbidity and socio‐demographic characteristics. Lowest 12‐month utilization rates were found for substance use disorders (15.6%; lifetime use 37.3%), highest for psychotic disorders (40.5%; lifetime 72.1%). Further, a considerable time lap was found between disorder onset and subsequent service use among the majority of cases with anxiety and mood disorders. This paper provides self‐reported epidemiological data on mental health service use in Germany, complementing administrative statistics and the predecessor mental health module of the German Health Interview and Examination Survey (GHS‐MHS) from 1998. Despite considerable changes in the mental health field in Germany and the existence of a comprehensive mental health care system without major financial barriers, we find no indications of substantially higher utilization rates for mental disorders as compared to other comparable European countries. Further, no indications of major overall changes in utilization rates are apparent. To pinpoint areas with unmet needs, more detailed analyses of the data are needed taking into account type, frequency, and adequacy of service use and treatment of mental disorders. Appropriately matched comparisons with the GHS‐MHS are needed to identify changes in patterns of utilization and interventions by type of disorder. Copyright © 2014 John Wiley & Sons, Ltd.     

Perception of first‐ and second‐order motion: Separable neurological mechanisms?

An unresolved issue in visual motion perception is how distinct are the processes underlying “first‐order” and “second‐order” motion. The former is defined by spatiotemporal variations of luminance and the latter by spatiotemporal variations in other image attributes, such as contrast or depth. Here we describe two neurological patients with focal unilateral lesions whose contrasting perceptual deficits on psychophysical tasks of “first‐order” and “second‐order” motion are related to the maps of the human brain established by functional neuroimaging and gross anatomical features. We used a relatively fine‐grained neocortical parcellation method applied to high‐resolution MRI scans of the patients' brains to illustrate a subtle, yet highly specific dissociation in the visual motion system in humans. Our results suggest that the two motion systems are mediated by regionally separate mechanisms from an early stage of cortical processing. Hum. Brain Mapping. 7:67–77, 1999. © 1999 Wiley‐Liss, Inc.     

Multifaceted roles of sphingosine‐1‐phosphate: How does this bioactive sphingolipid fit with acute neurological injury?

Sphingosine-1-phosphate (Sph-1-P) is an essential bioactive sphingolipid metabolite that has currently become the focus of intense interest. Sph-1-P is generated by the enzyme sphingosine kinase (SphK) in response to diverse stimuli, including growth factors, cytokines, and G-protein-coupled receptor (GPCR) agonists. Its precursor, sphingosine (Sph), is produced from the precursor ceramide (Cer) via a ceramidase (CDase) that is released from membrane sphingomyelin (SPM) by sphingomyelinases (SMase). Accumulating evidence indicates that Sph-1-P is the key regulatory lipid involved in the metabolism of sphingolipids and is involved in the control of numerous aspects of cell physiology, including mitogenesis, differentiation, migration, and apoptosis. These actions of Sph-1-P are mediated by a family of high-affinity S1P receptors, named S1P1-5, which are coupled differentially via G(i), G(q), G(12/13), and Rho to multiple effector systems, including adenylate cyclase, phospholipases C (PLC) and D (PLD), extracellular-signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nonreceptor tyrosine kinases. In this Review, we accumulate available evidence implying that sphingolipid signaling may represent a novel neuroprotective target to counteract the pathophysiology of acute brain and spinal cord injury in regard to apoptotic cell death mechanisms, mitochondrial dysfunction, lipid hydrolysis, and oxidative damage mechanisms. Furthermore, we discuss how Sph-1-P agonist approaches might be expected to increase the resistance of the central nervous system to injury by promoting neurotrophic activity, neurogenesis, and angiogenesis. On the other hand, antagonists of certain Sph-1-P-related activity might possess proregenerative effects via promotion of neurite growth and inhibition of astrogliotic scarring.     

Fate of microglia during HIV‐1 infection: From activation to senescence?

Microglia support productive human immunodeficiency virus type 1 (HIV‐1) infection and disturbed microglial function could contribute to the development of HIV‐associated neurocognitive disorders (HAND). Better understanding of how HIV‐1 infection and viral protein exposure modulate microglial function during the course of infection could lead to the identification of novel therapeutic targets for both the eradication of HIV‐1 reservoir and treatment of neurocognitive deficits. This review first describes microglial origins and function in the normal central nervous system (CNS), and the changes that occur during aging. We then critically discuss how HIV‐1 infection and exposure to viral proteins such as Tat and gp120 affect various aspects of microglial homeostasis including activation, cellular metabolism and cell cycle regulation, through pathways implicated in cellular stress responses including p38 mitogen‐activated protein kinase (MAPK) and nuclear factor κB (NF‐κB). We thus propose that the functions of human microglia evolve during both healthy and pathological aging. Aging‐associated dysfunction of microglia comprises phenotypes resembling cellular senescence, which could contribute to cognitive impairments observed in various neurodegenerative diseases. In addition, microglia seems to develop characteristics that could be related to cellular senescence post‐HIV‐1 infection and after exposure to HIV‐1 viral proteins. However, despite its potential role as a component of HAND and likely other neurocognitive disorders, microglia senescence has not been well characterized and should be the focus of future studies, which could have high translational relevance. GLIA 2017;65:431–446