Toxicity of inhaled particulate matter on the central nervous system: neuroinflammation,neuropsychological effects and neurodegenerative disease

Particulate matter (PM) combined with meteorological factors cause the haze, which brings inconvenience to people's daily life and deeply endanger people's health. Accumulating literature, to date, reported that PM are closely related to cardiopulmonary disease. Outpatient visits and admissions as a result of asthma and heart attacks gradually increase with an elevated concentration of PM. Owing to its special physicochemical property, the brain could be a potential target beyond the cardiopulmonary system. Possible routes of PM to the brain via a direct route or stimulation of pro‐inflammatory cytokines have been reported in several documents concerning toxicity of engineered nanoparticles in rodents. Recent studies have demonstrated that PM have implications in oxidative stress, inflammation, dysfunction of cellular organelles, as well as the disturbance of protein homeostasis, promoting neuron loss and exaggerating the burden of central nervous system (CNS). Moreover, the smallest particles (nano‐sized particles), which were involved in inflammation, reactive oxygen species (ROS), microglial activation and neuron loss, may accelerate the process of the neurodevelopmental disorder and neurodegenerative disease. Potential or other undiscovered mechanisms are not mutually exclusive but complementary aspects of each other. Epidemiology studies have shown that exposure to PM could bring about neurotoxicity and play a significant role in the etiology of CNS disease, which has been gradually corroborated by in vivo and in vitro studies. This review highlights research advances on the health effects of PM with an emphasis on neurotoxicity. With the hope of enhancing awareness in the public and calling for prevention and protective measures, it is a critical topic that requires proceeding exploration. Copyright © 2017 John Wiley & Sons, Ltd.     

Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II

Inhalation exposure to fine concentrated ambient particles (CAPs) increases cardiac oxidants by mechanisms involving modulation of the sympathovagal tone on the heart. Angiotensin-II is a potent vasoconstrictor and a sympatho-excitatory peptide involved in the regulation of blood pressure. We hypothesized that increases in angiotensin-II after fine particulate matter (PM) exposure could be involved in the development of cardiac oxidative stress. Adult rats were treated with an angiotensin-converting enzyme (ACE) inhibitor (benazepril^®), or an angiotensin receptor blocker (ARB; valsartan^®) before exposure to fine PM aerosols or filtered air. Exposures were carried out for 5 hours in the chamber of the Harvard fine particle concentrator (fine PM mass concentration: 440 ± 80 μg/m³). At the end of the exposure the animals were tested for in situ chemiluminescence (CL) of the heart, thiobarbituric acid reactive substances (TBARS) and for plasma levels of angiotensin-II. Also, continuous electrocardiogram (ECG) measurements were collected on a subgroup of exposed animals. PM exposure was associated with statistically significant increases in plasma angiotensin concentrations. Pre-treatment with the ACE inhibitor effectively lowered angiotensin concentration, whereas ARB treatment led to increases in angiotensin above the PM-only level. PM exposure also led to significant increases in heart oxidative stress (CL, TBARS), and a shortening of the T-end to T-peak interval on the ECG that were prevented by treatment with both the ACE inhibitor and ARB. These results show that ambient fine particles can increase plasma levels of angiotensin-II and suggest a role of the renin–angiotensin system in the development of particle-related acute cardiac events.     

CYTOKINES PRODUCTION IS ALTERED IN MICE EXPOSED TO AIRBORNE SUSPENDED MATTER

ABSTRACT

The production of IL-2 and IL-4 by thymocytes, spleen and axillary lymph node lymphocytes from female and male mice exposed to airborne suspended matter (ASM) was the scope of our investigations. Cytokines production by activated lymphocytes was determined by the estimation of the percentage of cells positive for intracellular cytokines and by the concentration of both cytokines secreted into the culture medium. Two models of mice exposure to ASM were used:1/ intraperitoneal injection (acute exposure), and 2/ oral exposure (subacute model). ASM exposure affected both IL-2 and IL-4 production and IL-2R α expression on activated lymphoid cells isolated from different lymphoid organs of both female and male mice. The effect was dependent on the route and duration of exposure, ASM dose and the age and sex of mice. A wide panel of changes is discussed. The prolonged exposure to ASM resulted in overproduction of IL-2 in both female and male mice and in overproduction of IL-4 in male mice. Acute exposure to ASM strongly affected IL-2 and IL-4 production, and the effect varied among lymphocytes from different lymphoid organs. Intracellular cytokines expression and the level of secreted cytokines seem to be good tools for the assessment of toxic effects of environmental pollution on the function of the immune system.     

Deformation of the corona radiata and internal capsule in normal pressure hydrocephalus

Background and purposeThe pathophysiology of the clinical manifestations in normal pressure hydrocephalus (NPH) remains obscure. Ventricular dilatation could generate forces on the paracentral fibers of the corona radiata (CR), hence interfering with their function and producing the classical clinical triad. The analysis of the regional displacement and deformation of the white matter bundles, forming the corona radiata and internal capsule, may clarify the relationship between ventricular dilatation and clinical manifestations in NPH.MethodAn experimental finite element (FE) analysis was used to simulate ventricular dilatation in 3 dimensions (3D) and to calculate the strain and deformation on the surrounding parenchyma. Magnetic resonance diffusion tensor imaging-based white matter tractography was then applied to retrieve the displacement and deformation exerted along various fiber bundles of the corona radiata and internal capsule. Anterior and posterior limb displacements and elongations were compared using a paired samples t-test.ResultsThe internal capsule, hence the corona radiata, of each cerebral hemisphere was segmented into anterior and posterior limbs. Mean displacements and elongations were calculated for each limb. Mean displacement was significantly larger in the anterior limb whereas mean deformation was larger in the posterior limb (P < 0.01).ConclusionThe present simulation demonstrates that ventricular dilatation does not have a homogeneous effect on the periventricular fibre tracts, with a particular load on the corticospinal tract. The affection of this tract remains thereby a potential factor in the generation of the NPH gait disorders.     

An insight into electrical resistivity of white matter and brain tumors

BackgroundThere is a lack of information regarding electrical properties of white matter and brain tumors.ObjectiveTo investigate the feasibility of in-vivo measurement of electrical resistivity during brain surgery and establish a better understanding of the resistivity patterns of brain tumors in correlation to the white matter.MethodsA bipolar probe was used to measure electrical resistivity during surgery in a prospective cohort of patients with brain tumors. For impedance measurement, the probe applied a constant current of 0.7 μA with a frequency of 140 Hz. The measurement was performed in the white matter within and outside peritumoral edema as well as in non-enhancing, enhancing and necrotic tumor areas. Resistivity values expressed in ohmmeter (Ω1m) were compared between different intracranial tissues and brain tumors.ResultsNinety-two patients (gliomas WHO II:16, WHO III:10, WHO IV:33, metastasis:33) were included. White matter outside peritumoral edema had higher resistivity values (13.3 ± 1.7 Ω1m) than within peritumoral edema (8.5 ± 1.6 Ω1m), and both had higher values than brain tumors including non-enhancing (WHO II:6.4 ± 1.3 Ω1m, WHO III:6.3 ± 0.9 Ω1m), enhancing (WHO IV:5 ± 1 Ω1m, metastasis:5.4 ± 1.3 Ω1m) and necrotic tumor areas (WHO IV:3.9 ± 1.1 Ω1m, metastasis:4.3 ± 1.3 Ω1m), p=<0.001. No difference was found between low-grade and anaplastic gliomas, p = 0.808, while resistivity values in both were higher than the highest values found in glioblastomas, p = 0.003 and p = 0.004, respectively.ConclusionsThe technique we applied enabled us to measure electrical resistivity of white matter and brain tumors in-vivo presumably with a significant effect with regard to dielectric polarization. Our results suggest that there are significant differences within different areas and subtypes of brain tumors and that white matter exhibits higher electrical resistivity than brain tumors.     

A paradigm for awake intraoperative memory mapping during forniceal stimulation

We report the case of a chess player with superior premorbid cognitive function who presented to the Cognitive Disorders clinic at the National Hospital for Neurology and Neurosurgery with a 2-year history of symptoms of possible memory loss. Initially the MRI scan appearance was within normal limits and his cognitive scores inside the normal range; subsequently his cognitive function deteriorated and he fulfilled criteria for Mild Cognitive Impairment (MCI) two years later. Unexpectedly he died of an unrelated illness seven months later and post mortem examination of the brain was carried out, revealing advanced Alzheimer’s disease (CERAD definite and NIA-Regan Institute high likelihood).

This case highlights the difficulties encountered in assessing patients with superior premorbid function in the early stages of Alzheimer’s disease, and reveals the value of serial MRI and neuropsychological assessment in detecting and monitoring early neurodegenerative disease.     

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

Objectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.

Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.

Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.

Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.