Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Since the second half of the last century, this traditional medicine has attracted the attention of scientists from multiple disciplines to elucidate its pharmacological properties. Of significant interest is curcumin’s role to treat neurodegenerative diseases including Alzheimer’s disease (AD), and Parkinson’s disease (PD) and malignancy. These diseases all share an inflammatory basis, involving increased cellular reactive oxygen species (ROS) accumulation and oxidative damage to lipids, nucleic acids and proteins. The therapeutic benefits of curcumin for these neurodegenerative diseases appear multifactorial via regulation of transcription factors, cytokines and enzymes associated with (Nuclear factor kappa beta) NFκB activity. This review describes the historical use of curcumin in medicine, its chemistry, stability and biological activities, including curcumin's anti-cancer, anti-microbial, anti-oxidant, and anti-inflammatory properties. The review further discusses the pharmacology of curcumin and provides new perspectives on its therapeutic potential and limitations. Especially, the review focuses in detail on the effectiveness of curcumin and its mechanism of actions in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and brain malignancies.
Curcumin; Alzheimer; Parkinson; glioblastoma; anti-oxidant; anti-inflammatory; reactive oxygen species
Acetylcholinesterase (AChE) (EC 188.8.131.52) is an important enzyme that breaks down of acetylcholine in synaptic cleft in neuronal junctions. Inhibition of AChE is associated with treatment of several diseases such as Alzheimer’s disease (AD), myasthenia gravis, and glaucoma as well as the mechanisms of insecticide and anthelmintic drugs. Several AChE inhibitors are available in clinical use currently for the treatment of AD; however, none of them has ability, yet, to seize progress of the disease. Consequently, an extensive research has been going on finding new AChE inhibitors. In this sense, natural inhibitors have gained great attention due to their encouraging effects toward AChE. In this review, promising candidate molecules with marked AChE inhibition from both plant and animal sources will be underlined.
Acetylcholinesterase; cholinesterase inhibition; neuroprotection; herbal; animal; microorganism
As acetylcholinesterase (AChE) inhibitors are an important therapeutic strategy in Alzheimer’s disease, efforts are being made in search of new molecules with anti-AChE activity. The fact that naturally-occurring compounds from plants are considered to be a potential source of new inhibitors has led to the discovery of an important number of secondary metabolites and plant extracts with the ability of inhibiting the enzyme AChE, which, according to the cholinergic hypothesis, increases the levels of the neurotransmitter acetylcholine in the brain, thus improving cholinergic functions in patients with Alzheimer’s disease and alleviating the symptoms of this neurological disorder. This review summarizes a total of 128 studies which correspond to the most relevant research work published during 2006-2012
(1st semester) on plant-derived compounds, plant extracts and essential oils found to elicit AChE inhibition.
Alzheimer’s Disease; acetylcholinesterase inhibitors; secondary metabolites; plant extracts; essential oils.
Alzheimer’s disease (AD) is the most common neurodegenerative disorder to date, with no curative or preventive therapy. Histopathological hallmarks of AD include deposition of β-amyloid plaques and formation of neurofibrillary tangles. Extent studies on pathology of the disease have made important discoveries regarding mechanism of disease and potential therapeutic targets. Many cellular changes including oxidative stress, disruption of Ca2+ homeostasis, inflammation, metabolic disturbances, and accumulation of unfolded/misfolded proteins can lead to programmed cell death in AD. Despite intensive research, only five approved drugs are available for the management of AD. Hence, there is a need to look at alternative therapies. Use of natural products and culinary herbs in medicine has gained popularity in recent years. Several natural substances with neuroprotective effects have been widely studied. Most of these compounds have remarkable antioxidant properties and act mainly by scavenging free radical species. Some of them increase cell survival and improve cognition by directly affecting amyloidogenesis and programmed cell death pathways. Further studies on these natural products and their mechanism of action, parallel with the use of novel pharmaceutical drug design and delivery techniques, enable us to offer an addition to conventional medicine. This review discussed some natural products with potential neuroprotective properties against Aβ with respect to their mechanism of action.
Alzheimer’s disease; Amyloid β; Apoptosis; Natural products; Neuroprotection; Tau protein.
Although the exact cause of neuronal loss in Parkinson’s disease is not known, evidence points to oxidative stress and the production of reactive oxygen species as the main events that occur in the substantia nigra pars compacta of the brain of parkinsonians. EGb761 is an extract of the leaves from the Ginkgo biloba tree that has been reported as an antioxidant and neuroprotective agent. The objective of this work was to perform a systematic review of the studies that analysed the effect of Ginkgo biloba extract on Parkinson’s disease or Parkinsonism. This research was conducted using the following databases: Medline, PsycInfo, Cinahl, Sigle, Lilacs, Scielo, Cochrane Library, and Embase. Initially, we selected 32 articles. After a more detailed analysis, only 10 articles remained. One of the hypotheses for the positive effect of EGb761 on Parkinson’s disease is the reduction or inhibition of monoamine-oxidase activity. This enzyme metabolises dopamine, inducing the formation of free radicals, which in turn damage nigrostriatal neurons. Another hypothesis is that the neuroprotective effect of EGb761 against 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and MPP+ toxins. As there are few studies on the effect of EGb761 on humans, this review could contribute new data to further the discussion of this issue.
EGb761; Ginkgo biloba extract; Parkinson’s disease; Parkinsonism; Systematic review.
Recently, mass spectrometric related techniques have been widely applied for the identification and quantification of neurochemicals and their metabolites in biofluids. This article presents an overview of mass spectrometric techniques applied in the detection of neurological substances and their metabolites from biological samples. In addition, the advances of chromatographic methods (LC, GC and CE) coupled with mass spectrometric techniques for analysis of neurochemicals in pharmaceutical and biological samples are also discussed.
Neurochemicals; LC-MS; GC-MS; CE-MS; MALDI-MS.
Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed.
Modified Multiple Platform; LTP; LTD; electrophysiology; anxiety; neurogenesis; nicotine; exercise.
Glutamate receptors of the N-methyl-D-aspartate (NMDA) type are involved in many cognitive processes, including behavior, learning and synaptic plasticity. For a long time NMDA receptors were thought to be the privileged domain of neurons; however, discoveries of the last 25 years have demonstrated their active role in glial cells as well. Despite the large number of studies in the field, there are many unresolved questions connected with NMDA receptors in glia that are still a matter of debate. The main objective of this review is to shed light on these controversies by summarizing results from all relevant works concerning astrocytes, oligodendrocytes and polydendrocytes (also known as NG2 glial cells) in experimental animals, further extended by studies performed on human glia. The results are divided according to the study approach to enable a better comparison of how findings obtained at the mRNA level correspond with protein expression or functionality. Furthermore, special attention is focused on the NMDA receptor subunits present in the particular glial cell types, which give them special characteristics different from those of neurons – for example, the absence of Mg2+ block and decreased Ca2+ permeability. Since glial cells are implicated in important physiological and pathophysiological roles in the central nervous system (CNS), the last part of this review provides an overview of glial NMDA receptors with respect to ischemic brain injury.
Astrocytes; ischemia; NG2 glia; NMDA receptors; oligodendrocyte progenitors; oligodendrocytes; polydendrocytes.
Similar to clinically used antidepressants, cannabinoids can also regulate anxiety and depressive symptoms. Although the mechanisms of these effects are not completely understood, recent evidence suggests that changes in endocannabinoid system could be involved in some actions of antidepressants. Chronic antidepressant treatment modifies the expression of CB1 receptors and endocannabinoid (EC) content in brain regions related to mood and anxiety control. Moreover, both antidepressant and cannabinoids activate mitogen-activated protein (MAP) kinase and phosphoinositide 3-kinase(PI3-K)/Akt or PKB signaling, intracellular pathways that regulate cell proliferation and neural cell survival. Facilitation of hippocampal neurogenesis is proposed as a common effect of chronic antidepressant treatment. Genetic or pharmacological manipulations of cannabinoid receptors (CB1 and CB2) or enzymes responsible for endocannabinoid-metabolism have also been shown to control proliferation and neurogenesis in the hippocampus. In the present paper we reviewed the studies that have investigated the potential contribution of cannabinoids and neurogenesisto antidepressant effects. Considering the widespread brain distribution of the EC system, a better understanding of this possible interaction could contribute to the development of therapeutic alternatives to mood and anxiety disorders.
Neurogenesis; antidepressant drugs; cannabinoids.
It is a common belief that voltage-gated calcium channels (VGCC) cannot carry toxic amounts of Ca2+ in neurons. Also, some of them as L-type channels are essential for Ca2+-dependent regulation of prosurvival gene-programs. However, a wealth of data show a beneficial effect of drugs acting on VGCCs in several neurodegenerative and neurovascular diseases. In the present review, we explore several mechanisms by which the “harmless” VGCCs may become “toxic” for neurons. These mechanisms could explain how, though usually required for neuronal survival, VGCCs may take part in neurodegeneration. We will present evidence showing that VGCCs can carry toxic Ca2+ when: a) their density or activity increases because of aging, chronic hypoxia or exposure to β-amyloid peptides or b) Ca2+-dependent action potentials carry high Ca2+ loads in pacemaker neurons. Besides, we will examine conditions in which VGCCs promote neuronal cell death without carrying excess Ca2+. This can happen, for instance, when they carry metal ions into the neuronal cytoplasm or when a pathological decrease in their activity weakens Ca2+-dependent prosurvival gene programs. Finally, we will explore the role of VGCCs in the control of nonneuronal cells that take part to neurodegeneration like those of the neurovascular unit or of microglia.
Neurovascular unit; voltage-gated Ca2+ channels; neurodegeneration; beta-amyloid; Parkinson’s disease; Alzheimer’s disease; Multiple Sclerosis.
Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (α2-α10) and 3 beta (β2-β4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize.
In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment.
Alzheimer disease; neurodegeneration; nicotinic receptors; Parkinson disease; pharmacology; subunit composition.
Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases.
Acetylcholine; acetylcholinesterase; Alzheimer’s disease drugs; carbamates; detoxification; irreversible inhibitors; organophosphates; reversible inhibitors.
The hypothalamus may be involved in regulating homeostasis, motivation, and emotional behavior by
controlling autonomic and endocrine activity. The hypothalamus communicates input from the thalamus to the pituitary
gland, reticular activating substance, limbic system, and neocortex. This allows the output of pituitary hormones to
respond to changes in autonomic nervous system activity. Environmental heat stress increases cutaneous blood flow and
metabolism, and progressively decreases splanchnic blood flow. Severe heat exposure also decreases mean arterial
pressure (MAP), increases intracranial pressure (ICP), and decreases cerebral perfusion pressure (CPP = MAP – ICP), all
of which lead to cerebral ischemia and hypoxia. Compared with normothermic controls, rodents with heatstroke have
higher hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol)
markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), proinflammatory cytokines (e.g.,
interleukin-1β and tumor necrosis factor-α), inducible nitric oxide synthase-dependent nitric oxide, and an indicator for
the accumulation of polymorphonuclear leukocytes (e.g., myeloperoxidase activity), as well as neuronal damage (e.g.,
apoptosis, necrosis, and autophagy) after heatstroke. Hypothalamic values of antioxidant defenses (e.g., glutathione
peroxidase and glutathione reductase), however, are lower. The ischemic, hypoxic, and oxidative damage to the
hypothalamus during heatstroke may cause multiple organ dysfunction or failure through hypothalamic-pituitary-adrenal
axis mechanisms. Finding the link between the signaling and heatstroke-induced hypothalamic oxidative and ischemic
damage might allow us to clinically attenuate heatstroke. In particular, free radical scavengers, heat shock protein-70
inducers, hypervolemic hemodilution, inducible nitric oxide synthase inhibitors, progenitor stem cells, flutamide,
estrogen, interleukin-1 receptor antagonists, glucocorticoid, activated protein C, and baicalin mitigate preclinical
Hypothalamus; heatstroke; hypotension; ischemia; hypoxia; oxidative stress; cytokines; inflammation; antioxidants; pharmacology.
The bed nucleus of the stria terminalis (BNST) is a heterogeneous and complex limbic forebrain structure, which plays an important role in controlling autonomic, neuroendocrine and behavioral responses. The BNST is thought to serve as a key relay connecting limbic forebrain structures to hypothalamic and brainstem regions associated with autonomic and neuroendocrine functions. Its control of physiological and behavioral activity is mediated by local action of numerous neurotransmitters. In the present review we discuss the role of the BNST in control of both autonomic and neuroendocrine function. A description of BNST control of cardiovascular and hypothalamus-pituitary-adrenal axisactivity at rest and during physiological challenges (stress and physical exercise) is presented. Moreover, evidence for modulation of hypothalamic magnocellular neurons activity is also discussed. We attempt to focus on the discussion of BNST neurochemical mechanisms. Therefore, the source and targets of neurochemical inputs to BNST subregions and their role in control of autonomic and neuroendocrine function is discussed in details.
BNST; cardiovascular function; extended amygdala; neurotransmitters; HPA axis; vasopressin; stress and physical exercise.
Data from many experiments has shown that serotonin2C (5-HT2C) receptor plays a role in the control of orofacial activity in rodents. Purposeless oral movements can be elicited either by agonists or inverse agonists implying a tight control exerted by the receptor upon oral activity. The effects of agonists has been related to an action of these drugs in the subthalamic nucleus and the striatum, the two input structures for cortical efferents to the basal ganglia, a group of subcortical structures involved in the control of motor behaviors. The oral effects of agonists are dramatically enhanced in case of chronic blockade of central dopaminergic transmission induced by neuroleptics or massive destruction of dopamine neurons. The mechanisms involved in the hypersensitized oral responses to 5-HT2C agonists are not clear and deserve additional studies. Indeed, while the oral behavior triggered by 5-HT2C drugs would barely correspond to the dyskinesia observed in humans, the clinical data have consistently postulated that 5-HT2C receptors could be involved in these aberrant motor manifestations.
Serotonin2c receptor; oral activity; neuroleptic; 6-hydroxydopamine lesion; hypersensitized oral responses.
Neuropsychiatric disorders are devastating mental illnesses with a high economic burden. The additional morbidity associated with social issues that arises along with the course of these diseases increases the need for a clear understanding of their etiopathogenesis to allow an implementation of novel pharmacological strategies. Yet a poor knowledge about interactions occurring at the glia-neuron interface in health and disease still hampers innovative discoveries, despite the fact that glia cells have been long described to actively participate in the regulation of brain circuits.
The purpose of this review was to collect the scattered literature on the involvement of glia cells in neuropsychiatric disorders and to describe how also these cells besides neurons might be responsive to current pharmacological interventions. We hope thereby to offer alternative approaches for investigations that may open avenues to search for new potential targets for drug discovery.
Astrocytes; microglia; neuropsychiatric disorders; oligodendrocytes; pharmacotherapy
Since attention deficit/hyperactivity disorder (ADHD) presents high prevalence among children, science has been researching alternative forms of treatment that do not involve medication. Objective: To evaluate the effects of polyunsaturated fatty acids (PUFAs) on attention deficit/hyperactivity disorder. Methods: We reviewed the articles published between 1980 and 2012 indexed in the databases PubMed, APA psychNET, Scopus and Web of Knowledge. Results: Initially 231 articles were selected, out of which 12 met the inclusion criteria. The articles selected reported a modest cognitive and behavioral improvement of the patients after treatment with low doses of PUFAs. Those results might be associated with the evaluation methodology, the doses of PUFAs administered or the duration of treatment.
Attention deficit/hyperactivity disorder; behavior; children; cognition; dietary supplements and polyunsaturated fatty acids.
The blood-brain barrier (BBB), a dynamic and complex barrier formed by endothelial cells, can impede the entry of unwanted substances – pathogens and therapeutic molecules alike – into the central nervous system (CNS) from the blood circulation. Taking into account the fact that CNS-related diseases are the largest and fastest growing unmet medical concern, many potential protein- and nucleic acid-based medicines have been developed for therapeutic purposes. However, due to their poor ability to cross the BBB and the plasma membrane, the above-mentioned bio-macromolecules have limited use in treating neurological diseases. Finding effective, safe, and convenient ways to deliver therapeutic molecules into the CNS is thus urgently required. In recent decades, much effort has been expended in the development of drug delivery technologies, of which cell-penetrating peptides (CPPs) have the most promising potential. The present review covers the latest advances in CPP delivery technology, and provides an update on their use in CNS-targeted drug delivery.
Central nervous system; blood-brain barrier; cell-penetrating peptides; drug delivery.
The renin-angiotensin system (RAS) in brain is a crucial regulator for physiological homeostasis and diseases of cerebrovascular system, such as ischemic stroke. Overactivation of brain Angiotensin-converting enzyme (ACE) - Angiotensin II (Ang II) - Angiotensin II type 1 receptor (AT1R) axis was found to be involved in the progress of hypertension, atherosclerosis and thrombogenesis, which increased the susceptibility to ischemic stroke. Besides, brain Ang II levels have been revealed to be increased in ischemic tissues after stroke, and contribute to neural damage through elevating oxidative stress levels and inducing inflammatory response in the ischemic hemisphere via AT1R. In recent years, new components of RAS have been discovered, including ACE2, Angiotensin-(1–7) [Ang-(1-7)] and Mas, which constitute ACE2-Ang-(1-7)-Mas axis. ACE2 converts Ang II to Ang-(1-7), and Ang-(1-7) binds with its receptor Mas, exerting benefical effects in cerebrovascular disease. Through interacting with nitric oxide and bradykinin, Ang-(1-7) could attenuate the development of hypertension and the pathologic progress of atherosclerosis. Besides, its antithrombotic activity also prevents thrombogenic events, which may contribute to reduce the risk of ischemic stroke. In addition, after ischemia insult, ACE2-Ang-(1-7)-Mas has been shown to reduce the cerebral infarct size and improve neurological deficits through its antioxidative and anti-inflammatory effects. Taken together, activation of the ACE2-Ang-(1-7)-Mas axis may become a novel therapeutic target in prevention and treatment of ischemia stroke, which deserves further investigations.
Renin-angiotensin system; Angiotensin-(1-7); Stroke; Neuroprotection; Oxidative stress.
Vasopressin (VP) and oxytocin (OT) are mainly synthesized in the magnocellular neurons of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. Axons from the magnocellular part of the PVN and SON project to neurohypophysis where VP and OT are released in blood to act like hormones. Axons from the parvocellular part of PVN project to extra-hypothalamic brain areas (median eminence, limbic system, brainstem and spinal cord) where VP and OT act like neurotransmitters/modulators. VP and OT act in complementary manner in cardiovascular control, both as hormones and neurotransmitters. While VP conserves water and increases circulating blood volume, OT eliminates sodium. Hyperactivity of VP neurons and quiescence of OT neurons in PVN underlie osmotic adjustment to pregnancy. In most vascular beds VP is a potent vasoconstrictor, more potent than OT, except in the umbilical artery at term. The vasoconstriction by VP and OT is mediated via V1aR. In some vascular beds, i.e. the lungs and the brain, VP and OT produce NO dependent vasodilatation. Peripherally, VP has been found to enhance the sensitivity of the baro-receptor while centrally, VP and OT increase sympathetic outflow, suppresse baro-receptor reflex and enhance respiration. Whilst VP is an important mediator of stress that triggers ACTH release, OT exhibits anti-stress properties. Moreover, VP has been found to contribute considerably to progression of hypertension and heart failure while OT has been found to decrease blood pressure and promote cardiac healing.
Vasopressin; oxytocin; respiration; blood pressure; baro-receptor reflex; stress; hypertension; heart failure.
Mild cognitive impairment (MCI) is a syndrome which, depending on various neurobiological, psychological and social factors, carries a high risk of developing into dementia. As far as diagnostic uncertainty and the heterogeneous underlying pathophysiological mechanisms are concerned, only limited therapeutic options are currently available. Clinical trials involving a wide range of substances have failed to show efficacy on primary and secondary outcome parameters. Most results reflect not only a lack of effectiveness of drug therapy but also methodological constraints in true prodromal Alzheimer´s disease (AD) based on clinical criteria. Biomarkers may help to identify MCI as a prodromal phase of dementia, so it is important to use them to improve specificity of case selection in future studies. For MCI as a prodromal syndrome of AD, clinical trials with disease modifying drugs that target underlying pathological mechanisms such as amyloid-beta accumulation and neurofibrillary tangle formation may help develop effective treatment options in the future. Alternative pharmacological approaches are currently being evaluated in ongoing phase 1 and phase 2 studies. Nevertheless, a lack of approved pharmacotherapeutic options has led to specific interventions that focus on patient education and life-style related factors receiving increasing attention.
Mild cognitive impairment; Alzheimer’s Dementia; Clinical Trials; Treatment.
The neurobiological etiopathogenesis of OCD is still obscure. Neuroimaging studies have been very influential in shaping neurobiological models of OCD. Investigations performed within last twenty years have revealed some important findings and proposed that specific cortico-striato-thalamic circuits are involved in the mediation of its symptoms. The effects of antiobsessional drugs and cognitive behavioral therapy on structural and functional imaging have been evaluated in limited size of investigations. In structural investigations, in summary, it was found key brain regions in the pathophysiology of OCD and amygdala to change volumetrically by treatment. In functional and neurochemical investigations, by using different treatment modalities, cortico-striatal function disablements and NAA changes in a variety of brain regions were reported. In this paper, these limited data are reviewed. It is clear that there is so many things to be performed in the future researches on the effects of therapy on brains of the patients with OCD.
OCD; Structurel; MRI; MRS; fMRI.
Until recently, epilepsy medical therapy is usually limited to anti-epileptic drugs (AEDs). However, approximately 1/3 of epilepsy patients, described as drug-resistant epilepsy (DRE) patients, still suffer from continuous frequent seizures despite receiving adequate AEDs treatment of sufficient duration. More recently, with the remarkable progress of immunology, immunity and inflammation are considered to be key elements of the pathobiology of epilepsy. Activation of inflammatory processes in brain tissue has been observed in both experimental seizure animal models and epilepsy patients. Anti-inflammatory and immunotherapies also showed significant anticonvulsant properties both in clinical and in experimental settings. The above emerging evidence indicates that modulation of immunity and inflammatory processes could serve as novel specific targets to achieve potential anticonvulsant effects for the patients with epilepsy, especially DRE. Herein we review the recent evidence supporting the role of inflammation in the development and perpetuation of seizures, and also discuss the recent achievements in modulation of inflammation and immunotherapy applied to the treatment of epilepsy. Apart from medical therapy, we also discuss the influences of surgery, ketogenic diet, and electroconvulsive therapy on immunity and inflammation in DRE patients. Taken together, a promising perspective is suggested for future immunomodulatory therapies in the treatment of patients with DRE.
Immunity; Inflammation; Drug-Resistant Epilepsy; Auto-antibodies; Cytokines.