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Lakhan S.E.,Cleveland Clinic | Avramut M.,Global Neuroscience Initiative Foundation | Tepper S.J.,Cleveland Clinic
Headache | Year: 2013

Modern imaging methods provide unprecedented insights into brain structure, perfusion, metabolism, and neurochemistry, both during and between migraine attacks. Neuroimaging investigations conducted in recent decades bring us closer to uncovering migraine as a multifaceted, primarily central nervous system disorder. Three main categories of structural and functional brain changes are described in this review, corresponding to the migrainous aura, ictal headache, and interictal states. These changes greatly advance our understanding of multiple pathophysiologic underpinnings of migraine, from central "migraine generating" loci, to cortical spreading depression, intimate mechanisms underlying activation of neuronal pain pathways in vulnerable patients, central sensitization, and chronification. Structural imaging begins to explain the complex connections between migraine and cerebral vascular events, white matter lesions, grey matter density alterations, iron deposition, and microstructural brain damage. Selected structural and functional alterations of brain structures, as identified with imaging methods, may represent the foundation of new diagnostic strategies and serve as markers of therapeutic efficacy. © 2012 American Headache Society.

Lakhan S.E.,Global Neuroscience Initiative Foundation | Lakhan S.E.,Cleveland Clinic | Caro M.,Cleveland Clinic | Hadzimichalis N.,Global Neuroscience Initiative Foundation
Frontiers in Psychiatry | Year: 2013

N-Methyl-D-aspartate (NMDA) receptors play a variety of physiologic roles andtheir proper signaling is essential for cellular homeostasis. Any disruption in this pathway, leading to either enhanced or decreased activity, may result in the manifestation of neuropsychiatric pathologies such as schizophrenia, mood disorders,substance induced psychosis, Huntington's disease, Alzheimer's disease, and neuropsychiatric systemic lupus erythematosus. Here, we explore the notion that the overlap in activity of at least one biochemical pathway, the NMDA receptor pathway, may be the link to understanding the overlap in psychotic symptoms between diseases.This review intends to present a broad overview of those neuropsychiatric disorders for which alternations in NMDA receptor activity is prominent thus suggesting that continued direction of pharmaceutical intervention to this pathway may present a viable option for managing symptoms.© 2013 Lakhan, Caro and Hadzimichalis.

Lakhan S.E.,Global Neuroscience Initiative Foundation | Vieira K.F.,Global Neuroscience Initiative Foundation
Nutrition Journal | Year: 2010

Background. Over the past several decades, complementary and alternative medications have increasingly become a part of everyday treatment. With the rising cost of prescription medications and their production of unwanted side effects, patients are exploring herbal and other natural remedies for the management and treatment of psychological conditions. Psychological disorders are one of the most frequent conditions seen by clinicians, and often require a long-term regimen of prescription medications. Approximately 6.8 million Americans suffer from generalized anxiety disorder. Many also suffer from the spectrum of behavioural and physical side effects that often accompany its treatment. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal. Methods. An electronic and manual search was performed through MEDLINE/PubMed and EBSCO. Articles were not discriminated by date of publication. Available clinical studies published in English that used human participants and examined the anxiolytic potential of dietary and herbal supplements were included. Data were extracted and compiled into tables that included the study design, sample population, intervention, control, length of treatment, outcomes, direction of evidence, and reported adverse events. Results. A total of 24 studies that investigated five different CAM monotherapies and eight different combination treatments and involved 2619 participants met the inclusion criteria and were analyzed. There were 21 randomized controlled trials and three open-label, uncontrolled observational studies. Most studies involved patients who had been diagnosed with either an anxiety disorder or depression (n = 1786). However, eight studies used healthy volunteers (n = 877) who had normal levels of anxiety, were undergoing surgery, tested at the upper limit of the normal range of a trait anxiety scale, had adverse premenstrual symptoms or were peri-menopausal, reported anxiety and insomnia, or had one month or more of elevated generalized anxiety. Heterogeneity and the small number of studies for each supplement or combination therapy prevented a formal meta-analysis. Of the randomized controlled trials reviewed, 71% (15 out of 21) showed a positive direction of evidence. Any reported side effects were mild to moderate. Conclusions. Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava and combinations of L-lysine and L-arginine as treatments for anxiety symptoms and disorders. Magnesium-containing supplements and other herbal combinations may hold promise, but more research is needed before these products can be recommended to patients. St. John's wort monotherapy has insufficient evidence for use as an effective anxiolytic treatment. © 2010 Lakhan and Vieira; licensee BioMed Central Ltd.

Lakhan S.E.,Global Neuroscience Initiative Foundation | Kirchgessner A.,Global Neuroscience Initiative Foundation | Kirchgessner A.,Seton Hall University
Journal of Translational Medicine | Year: 2011

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell. © 2011 Lakhan and Kirchgessner; licensee BioMed Central Ltd.

Lakhan S.E.,Global Neuroscience Initiative Foundation | Avramut M.,Global Neuroscience Initiative Foundation
Pain Research and Treatment | Year: 2012

Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases that mediate extracellular matrix turnover and associated processes, such as cell survival, growth, and differentiation. This paper discusses important functions of MMP in the normal and injured nervous system, focusing on the role played by these proteases in neurological pain syndromes, most prominently in neuropathic pain and migraine headaches. In the past decade, metalloproteinases emerged as key modulators of neuropathic pain, with MMP-9 acting as an initiator of the neuropathic cascade. Increased MMP activity was detected in migraine patients, independent of aura, in tight association with metabolic derangements. The therapeutic implications of MMP inhibition are considered in the context of neurogenic pain regulation. © 2012 Shaheen E. Lakhan and Mihaela Avramut.

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