Central Nervous System Malfunction Research Articles

An Overview of Air Pollution's Environmental and Health Consequence

The problem of air pollution has ramifications for human health, the environment, and a variety of living sectors. Modern technology has resulted in air pollution and its damaging effects, while also driving the world to make every effort to overcome its negative repercussions. The origin, chemical composition, size, and mode of discharge inside or outdoor environs have all been proven to be air pollutants. Industrial, commercial, mobile, urban, regional, farm, and natural sources of indoor pollutants include cooking and combustion, particle matter rehabilitation, materials used for materials, temperature control, and consumer items, smoking, heating, and organic compounds. Indoor Pollutant Sources Air pollution has an impact on the body, including respiratory systems and heart disorders. Asthmatics, bronchiolitis, lung disease, cardiovascular problems, central nervous system malfunction, and skin conditions are the most common respiratory disorders, as are chronic obstructive pulmonary disease (COPD). The challenges posed by outdoor air pollution are public health risks such as cardiovascular disease, respiratory ailments, COPD, and world-class asymmetry. The impacts of human activities on air quality and climate change may be seen at several sizes, ranging from urban to regional to continental to global. Rapid population growth and increased energy consumption are the principal drivers of massive amounts of hazardous chemicals and greenhouse gases entering the atmosphere, with serious consequences for health and the environment.

Knowledge of Primary School Teachers Regarding Learning Disorders among Children at Schools of Satara District

Introduction: “Learning disorder is a general term that refers to a group of disorders manifested by difficulty in the acquisition and use of listening, speaking, reading, writing, & mathematical abilities. These disorders are inherent to the person supposed to be because of central nervous system malfunction. Most students who undergo from learning disorders will not be recognized before standard 3-4 of primary school since their teachers don’t have adequate knowledge about learning disorder. Teachers are the child’s first contact person in school and the perfect person to find out a learning difficulty. Unluckily, most either pay no attention to the problem or blame it on the child’s personality.2 Methodology: The study was designed in the form of non-experimental descriptive type. Study comprised of 316 primary school teachers from conveniently selected schools at Satara district. Result: Majority of the teachers was belongs to 41 to 58 age groups 203(64.24%), 199(62.97%) were females, 277(87.65) were Hindu, 301(95.25%) teachers was married, 214(67.72%) teachers were having educational qualification of D.Ed., 243(78.89%) teachers was having above 11 years of experience. 166(52.26%) of the subject had poor knowledge,146(46.20%) teachers had average knowledge & 04(1.26%) had good knowledge. Conclusion: Present study showed the need for intensive training of primary school teachers on learning disorders.

Marine Mammals' NMDA Receptor Structure: Possible Adaptation to High Pressure Environment.

Divers that are exposed to high pressure (HP) above 1.1 MPa suffer from High Pressure Neurological Syndrome (HPNS), which is implicated with central nervous system (CNS) malfunction. Marine mammals performing extended and deep breath-hold dives are exposed to almost 20 MPa without apparent HPNS symptoms. N-methyl-D-aspartate receptor (NMDAR) has repeatedly been implicated as one of the major factors in CNS hyperexcitability as part of HPNS. Electrophysiological studies in rat brain slices at He HP showed a significant increase in the synaptic NMDAR response, followed by postsynaptic excitability changes. Molecular studies of Rattus norvegicus NMDARs have revealed that different subunit combinations of the NMDAR exhibit different, increased or decreased, current responses under He HP conditions. The purpose of the present research was to disclose if the breath-hold deep diving mammals exhibit NMDAR structural modifications related to HP. We used sequence alignment and homology structure modeling in order to compare deep diving marine mammals’ NMDARs to those of terrestrial mammals. We discovered that deep diving mammals have a special tertiary TMD structure of the GluN2A subunit that differs from that of the terrestrial mammals. In addition, the GluN2A subunit has a group of four conserved a.a. substitutions: V68L (N-terminal domain, NTD) and V440I (agonist-binding domain, ABD) are cetacean specific, E308D (N-terminal domain, NTD) and I816V (transmembrane domain, TMD) were also singularly found in some terrestrial mammals. Since I816V is localized in M4 α-helix region, which is critical for NMDAR activation and desensitization, we hypothesize that the presence of all 4 substitutions rather than a single one, is the combination that may enable HP tolerance. Furthermore, additional special substitutions that were found in the marine mammals’ NTD may affect the Zn2+ binding site, suggesting less or no voltage-independent inhibition by this ion. Our molecular studies of NMDARs containing the GluN2A subunit showed that HP removal of the Zn2+ voltage-independent inhibition could be the mechanism explaining its current increase at HP. Thus, this mechanism could play a crucial role in the CNS hyperexcitability at HP. Less or no voltage-independent Zn2+ inhibition, different conformations of the TMD, and special mutation in the M4 α-helix region of cetaceans’ NMDAR, may give them the advantage they need in order to perform such deep dives without CNS malfunction.

α-Lipoic acid alleviates pentetrazol-induced neurological deficits and behavioral dysfunction in rats with seizures via an Nrf2 pathway

Epilepsy (EP) is a type of chronic brain disease characterized by transient central nervous system malfunction which is the result of neuron paradoxical discharge in the brain.

Delayed recovery from unusual and late-onset complications of organophosphate poisoning

Self-poisoning with organophosphate (OP) pesticides has become a serious problem in developing countries. OPs inhibit acetylcholinesterase, leading to the accumulation of acetylcholine, which, in turn, leads to autonomic, somatic and central nervous system malfunction. The clinical features of OP toxicity are defined as acute cholinergic crisis; other manifestations include intermediate and delayed polyneuropathy. Here, we report a case of a 75-year-old man who allegedly intentionally ingested OP insecticide and who presented with cardiac arrest complicated by intermediate syndrome and delayed organophosphorusinduced polyneuropathy. All complications occurred during the course of management, for example unusual complete heart block and late onset of complete limb paralysis reported in this case. This report highlights uncommon complications of OP poisoning and that early awareness of these complications by the physicians and intensive supportive treatment is the key to successful management.

Radiation damage to neuronal cells: Simulating the energy deposition and water radiolysis in a small neural network

Radiation damage to the central nervous system (CNS) has been an on-going challenge for the last decades primarily due to the issues of brain radiotherapy and radiation protection for astronauts during space travel. Although recent findings revealed a number of molecular mechanisms associated with radiation-induced impairments in behaviour and cognition, some uncertainties exist in the initial neuronal cell injury leading to the further development of CNS malfunction. The present study is focused on the investigation of early biological damage induced by ionizing radiations in a sample neural network by means of modelling physico-chemical processes occurring in the medium after exposure. For this purpose, the stochastic simulation of incident particle tracks and water radiation chemistry was performed in realistic neuron phantoms constructed using experimental data on cell morphology. The applied simulation technique is based on using Monte-Carlo processes of the Geant4-DNA toolkit. The calculations were made for proton, 12C, and 56Fe particles of different energy within a relatively wide range of linear energy transfer values from a few to hundreds of keV/μm. The results indicate that the neuron morphology is an important factor determining the accumulation of microscopic radiation dose and water radiolysis products in neurons. The estimation of the radiolytic yields in neuronal cells suggests that the observed enhancement in the levels of reactive oxygen species may potentially lead to oxidative damage to neuronal components disrupting the normal communication between cells of the neural network.

Structural bases for central nervous system malfunction in the quaking mouse: Dysmyelination in a potential model of schizophrenia

The dysmyelinating mouse mutant quaking (qk) is thought to be a model of schizophrenia based on diminution of CNS myelin (Andreone et al., 2007) and downregulation of the Qk gene (Haroutunian et al., 2006) in the brains of schizophrenic patients. The purpose of this study was to identify specific structural defects in the qk mouse CNS that could compromise physiologic function and that in humans might account for some of the cognitive defects characteristic of schizophrenia. Ultrastructural analysis of qk mouse CNS myelinated fibers shows abnormalities in nodal, internodal, and paranodal regions, including marked variation in myelin thickness among neighboring fibers, spotty disruption of paranodal junctions, abnormal distribution of nodal and paranodal ion channel complexes, generalized thinning and incompactness of myelin, and on many axonal profiles complete absence of myelin. These structural defects are likely to cause abnormalities in conduction velocity, synchrony of activation, temporal ordering of signals, and other physiological parameters. We conclude that the structural abnormalities described are likely to be responsible for significant functional impairment both in the qk mouse CNS and in the human CNS with comparable myelin pathology.

Neurotoxoplasmosis diagnosis for HIV-1 patients by real-time PCR of cerebrospinal fluid

Encephalitis caused by Toxoplasma gondii is the most common cause of central nervous system damage in patients with acquired immunodeficiency syndrome (AIDS). Toxoplasma may infect any of the brain cells, thus leading to non-specific neurotoxoplasmosis clinical manifestations including focused or non-focused signs and symptoms of central nervous system malfunction. Clinical development ranges from insidious display during weeks to experiencing acute general confusion or ultimately fatal onset. Cerebral toxoplasmosis occurs in advanced stages of immunodeficiency, and the absence of anti-toxoplasmosis antibodies by the immunofluorescence method does not allow us to rule out its diagnosis. As specific therapy begins, diagnosis confirmation is sought through clinical and radiological response. There are few accurate diagnosis methods to confirm such cases. We present a method for T. gondii DNA detection by real time PCR-Multiplex. Fifty-one patients were evaluated; 16 patients had AIDS and a presumptive diagnosis for toxoplasmosis, 23 patients were HIV-positive with further morbidities except neurotoxoplasmosis, and 12 subjects were HIV-negative control patients. Real time PCR-Multiplex was applied to these patients' cephalorachidian liquid with a specific T. gondii genome sequence from the 529bp fragment. This test is usually carried out within four hours. Test sensitivity, specificity, positive predictive value, and negative predictive value were calculated according to applicable tables. Toxoplasma gondii assay by real time Multiplex of cephalorachidian fluid was positive for 11 out of 16 patients with AIDS and a presumptive diagnosis for cerebral toxoplasmosis, while none of the 35 control patients displayed such a result. Therefore, this method allowed us to achieve 68.8% sensitivity, 100% specificity, 100% positive predictive value, and 87.8% negative predictive value. Real time PCR on CSF allowed high specificity and good sensitivity among patients who presumably had cerebral toxoplasmosis. Since this is a low invasive method, it could be included in the diagnosis algorithm of patients with AIDS and central nervous system damage.

Developments in the scientific and clinical understanding of fibromyalgia

Our understanding of fibromyalgia (FM) has made significant advances over the past decade. The current concept views FM as the result of central nervous system malfunction resulting in amplification of pain transmission and interpretation. Research done over the past years has demonstrated a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FM. Various external stimuli such as infection, trauma and stress may contribute to the development of the syndrome. The management of FM requires an integrated approach combining pharmacological and nonpharmacological modalities. The recent Food and Drugs Administration approval of pregabalin, duloxetine and milnacipran as medications for FM may herald a new era for the development of medications with higher specificity and efficacy for the condition. As our understanding of the biological basis and the genetic underpinning of FM increases, we hope to gain a better understanding of the true nature of the disorder, to better classify patients and to attain more rational therapeutic modalities.

Somatosensory Hypersensitivity in the Referred Pain Area in Patients With Chronic Biliary Pain and a Sphincter of Oddi Dysfunction: New Aspects of an Almost Forgotten Pathogenetic Mechanism

Somatosensory hyperalgesia in the referred pain area (RPA) in patients with acute or chronic abdominal pain syndromes may result from the convergence of nerve fibers from visceral and somatic tissues at the spinal and supraspinal levels. Chronic biliary pain in patients with the postcholecystectomy syndrome (i.e., biliary hypersensitivity) may be explained by persistent hyperexcitability of neurons in the central nervous system (CNS). The aim of this study was to evaluate the cutaneous neural sensory perception in the RPA in patients with chronic postcholecystectomy biliary pain and a sphincter of Oddi (SO) dysfunction (SOD). Forty-two patients with persistent biliary pain and suspected SOD, 27 age-matched healthy volunteers, and 18 age-matched asymptomatic cholecystectomized controls were prospectively investigated by quantitative sensory testing (Neurometer CPT). The biliary symptoms and the severity of pain were classified on a visual analog pain severity scale system via a previously validated and standardized questionnaire. The patients helped the doctors locate the RPA in the right upper quadrant. The sensory detection threshold was determined noninvasively (Neurometer CPT) with transcutaneous electrical stimulation at 5, 250, and 2,000 Hz, and different current intensities (range from 0.01 to 9.99 mA) applied in a single (patient) blinded method. These three frequencies selectively excite small unmyelinated (C fibers), small myelinated (A-delta), and large myelinated (A-beta) fibers, which transmit dull pain, sharp pain, and touch, respectively. The contralateral region of the abdomen left upper quadrant served as the control area. The sensory current perception threshold ratio (SCPTR) of the data measured in the contralateral area and the RPA was calculated. The SCPTRs in the definite SOD patients with biliary pain, healthy volunteers, the asymptomatic cholecystectomized controls, and the symptomatic cholecystectomized patients but without SOD were 2.32 +/- 1.4 versus 1.06 +/- 0.24 versus 0.97 +/- 0.16 versus 0.83 +/- 0.35 at 2,000 Hz; 2.19 +/- 1.0 versus 1.01 +/- 0.26 versus 1.02 +/- 0.25 versus 0.88 +/- 0.35 at 250 Hz; and 2.19 +/- 1.1 versus 1.12 +/- 0.26 versus 0.99 +/- 0.37 versus 0.84 +/- 0.32 at 5 Hz, respectively. Significant hypersensitivity was detected in the RPA at different stimulation frequencies in the SOD patients with biliary pain versus the cholecystectomized controls: at 5 Hz: P = 0.00001; at 250 Hz: P = 0.00001; and at 2,000 Hz: P = 0.0001, respectively. Continuous visceral pain (biliary pain) caused by local inflammatory/sensitizing processes or a CNS malfunction could lead to significant hypersensitivity of the peripheral nociceptive nerve fibers in SOD patients. Postcholecystectomy pain may be explained by persistent hyperexcitability of the nociceptive neurons in the CNS with or without objective motility disorders of the SO.

Guide to Understanding Drosophila Models of Neurodegenerative Diseases

In the decade since human genes associated with neurodegenerative disease were first used in flies to create pathological phenotypes [1–5], a minor industry has sprung up using flies as a model to study the mechanisms underlying central nervous system malfunction in humans. Why study neurodegeneration in flies? Their small size, rapid generation time, and low costs for maintenance as compared to mammalian models make them attractive enough. The true value of flies to the study of neurodegenerative disorders, however, is their capacity to provide a platform for unbiased genetic screens to identify components of pathological pathways. If expression of pathological human genes in the fly successfully generates an abnormal phenotype, such as slowed motor activity or degeneration of the retina, this phenotype can then be used in conjunction with the rich genetic toolbox that Drosophila researchers have developed over the last 90 years to identify pathways that contribute to this degeneration. This approach is unbiased, i.e., it does not depend upon prior assumptions about mechanisms underlying disease, and genome-wide screens can be carried out in the fly that would be difficult if not impossible to carry out using mouse models. Key to such an approach is how similar flies are to humans. A stunning 75% (approximately) of the genes implicated in human genetic disorders have at least one homolog in the fruit fly (see http://superfly.ucsd.edu/homophila/ for further information). In general, fundamental aspects of cell biology relevant to processes as diverse as cell cycle regulation, synaptogenesis, membrane trafficking, and cell death are similar in Drosophila and humans. Of course, there are important differences between flies and humans; for example, the circulatory system is much simpler in the fly, and cognitive processes are much less complex. Nonetheless, the fly has proved itself as a useful adjunct to mammalian models for neurodegenerative diseases. A variety of neurodegenerative disorders have been modeled in the fly (for reviews, see [6–10]); perhaps the best established and most robust models are those associated with a group of inherited disorders that are all caused by the same mechanism: expansion of an unstable CAG repeat resulting in expression of proteins containing expanded polyglutamine tracts. The best known of these disorders is Huntington disease, but there are a number of somewhat similar disorders also caused by a CAG repeat expansion that are collectively referred to as the spinocerebellar ataxias (SCAs). These are generally adult-onset, progressive neurodegenerative disorders that feature impaired coordination due to degeneration of the cerebellum [11]. The different SCAs may have slightly different symptoms in addition to impaired coordination, such as tremor in SCA type 2 (SCA2) similar to that seen in Parkinson disease or muscular atrophy due to nerve damage in SCA3, but all are inexorably progressive. Some symptoms, such as impaired swallowing or gait ataxias, may be mildly improved by medications, assistive devices, or physical therapy, but no disease-modifying treatments exist. The proteins in which the polyglutamine expansions occur in each disorder show no obvious similarities and are referred to as ataxins 1, 2, 3, etc. (Atx1, Atx2, Atx3, etc.). Although the syndromic classifications of neurodegenerative disorders that began to be developed in the nineteenth century focused on distinctions between different disorders, more recent pathological and molecular analyses have begun to identify commonalities between what have traditionally been thought of as distinct diseases, as well as crosstalk between seemingly unrelated disease-associated proteins. In this issue of PLoS Biology, Derek Lessing and Nancy Bonini describe an interaction in which Atx2 contributes to the pathogenicity of Atx3 [12]. This report comes on the heels of similar work by Juan Botas and colleagues describing an interaction between Atx2 and Atx1 [13]. Here, I set out to demystify the creation and deployment of fly models of neurodegenerative diseases, and to put the current studies of interaction among ataxins in perspective.

Effects of axonal injury on ganglion cell survival and glutamate homeostasis

Axonal trauma leads to a series of pathologic events that can culminate in neuronal death. Optic nerve crush can be used to explore histologic and molecular changes in traumatic central nervous system malfunction. Although the precise mechanisms of retinal ganglion cell death after optic nerve crush have not been elucidated, glutamate antagonists can protect retinal ganglion cells after axotomy. We, therefore, evaluated the effect of optic nerve crush on levels of extracellular glutamate. Ganglion cell survival and extracellular glutamate levels were assessed from 1 to 28 days after optic nerve crush in Long–Evans rats. Optic nerve crush led to a rise in extracellular glutamate; this rise was blocked by treatment with memantine, riluzole, and nimodipine. Partial optic nerve crush leads to an increase in vitreal glutamate, perhaps through release of intracellular contents. This released glutamate can contribute to additional ganglion cell loss. Future work will help to additionally unravel the steps by which axotomy induces excitotoxic damage to ganglion cells, and perhaps indicate protective interventions.

Protective and Curative Effects of Rifampicin in Acanthamoeba Meningitis of the Mouse

BALB/c mice inoculated nasally with Acanthamoeba culbertsoni, resulting in amebic encephalitis and death 3-7 days, were treated with rifampicin prophylactically (daily for 2 days with 75 and 100 mg/kg) and after infection (daily for 5 days with doses of 10-100 mg/kg). Prophylactic treatment resulted in full protection against infection, as assessed by absence of symptoms of central nervous system malfunction and negative brain culture 10 days after inoculation. Curative treatment was effective at the same doses; however, at doses of 10, 25, and 50 mg/kg, only two of six animals were free of symptoms and infection.

Effect of neonatal thyroid deficiency on the catecholamine, substance P, and thyrotropin-releasing hormone contents of discrete rat brain nuclei.

The effects of neonatal thyroidectomy and thyroid hormone replacement therapy on the development of catecholamine-, TRH-, and substance P-containing neurons in discrete rat brain nuclei were studied. Newborn male rats were rendered hypothyroid by the injection of 125 muCi 131I and, after 45 days, were compared with normal littermate controls and 131I-injected animals subsequently maintained on T4 injections. The peptide or catecholamine content of discrete brain nuclei removed by punches of frozen brain slices was measured by RIA or radioenzymatic assay, respectively. The success of the thyroidectomy was verified by criteria of weight, length, plasma T4, and pituitary GH content. Animals receiving T4 replacement therapy were indistinguishable from normal littermates. Substance P was measured in 32 different brain nuclei and was significantly increased in 19 of these areas in hypothyroid animals. No changes in norepinephrine were detected, and the dopamine content of all but 3 brain nuclei was increased by thyroidectomy. The TRH concentration was drastically reduced in the median eminence of hypothyroid animals and also changed in 3 other extrahypothalamic areas. All of the changes seen in catecholamine, TRH, and substance P distribution in hypothyroid animals were completely reversed by T4 replacement therapy. These results demonstrate changes in brain peptide neurotransmitters during the hypothyroid state and open new vistas for comprehension of biochemical mechanisms underlying central nervous system malfunction.