Alcohol Pathophysiology

2010 ◽  
Vol 24 (4) ◽  
pp. 215-230 ◽  
Author(s):  
Claude Tomberg

There is no specialized alcohol addiction area in the brain; rather, alcohol acts on a wide range of excitatory and inhibitory nervous networks to modulate neurotransmitters actions by binding with and altering the function of specific proteins. With no hemato-encephalic barrier for alcohol, its actions are strongly related to the amount of intake. Heavy alcohol intake is associated with both structural and functional changes in the central nervous system with long-term neuronal adaptive changes contributing to the phenomena of tolerance and withdrawal. The effects of alcohol on the function of neuronal networks are heterogeneous. Because ethanol affects neural activity in some brain sites but is without effect in others, its actions are analyzed in terms of integrated connectivities in the functional circuitry of neuronal networks, which are of particular interest because of the cognitive interactions discussed in the manuscripts contributing to this review. Recent molecular data are reviewed as a support for the other contributions dealing with cognitive disturbances related to alcohol acute and addicted consumption.

2021 ◽  
Vol 17 (2) ◽  
pp. 6-15
Author(s):  
L.A. Dziak ◽  
O.S. Tsurkalenko ◽  
K.V. Chekha ◽  
V.M. Suk

Coronavirus infection is a systemic pathology resulting in impairment of the nervous system. The involvement of the central nervous system in COVID-19 is diverse by clinical manifestations and main mechanisms. The mechanisms of interrelations between SARS-CoV-2 and the nervous system include a direct virus-induced lesion of the central nervous system, inflammatory-mediated impairment, thrombus burden, and impairment caused by hypoxia and homeostasis. Due to the multi-factor mechanisms (viral, immune, hypoxic, hypercoagulation), the SARS-CoV-2 infection can cause a wide range of neurological disorders involving both the central and peripheral nervous system and end organs. Dizziness, headache, altered level of consciousness, acute cerebrovascular diseases, hypogeusia, hyposmia, peripheral neuropathies, sleep disorders, delirium, neuralgia, myalgia are the most common signs. The structural and functional changes in various organs and systems and many neurological symptoms are determined to persist after COVID-19. Regardless of the numerous clinical reports about the neurological and psychiatric symptoms of COVID-19 as before it is difficult to determine if they are associated with the direct or indirect impact of viral infection or they are secondary to hypoxia, sepsis, cytokine reaction, and multiple organ failure. Penetrated the brain, COVID-19 can impact the other organs and systems and the body in general. Given the mechanisms of impairment, the survivors after COVID-19 with the infection penetrated the brain are more susceptible to more serious diseases such as Parkinson’s disease, cognitive decline, multiple sclerosis, and other autoimmune diseases. Given the multi-factor pathogenesis of COVID-19 resulting in long-term persistence of the clinical symptoms due to impaired neuroplasticity and neurogenesis followed by cholinergic deficiency, the usage of Neuroxon® 1000 mg a day with twice-day dosing for 30 days. Also, a long-term follow-up and control over the COVID-19 patients are recommended for the prophylaxis, timely determination, and correction of long-term complications.


2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.


Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 314 ◽  
Author(s):  
Nicole Blanshan ◽  
Hollis Krug

Chronic osteoarthritis pain is an increasing worldwide problem. Treatment for osteoarthritis pain is generally inadequate or fraught with potential toxicities. Botulinum toxins (BoNTs) are potent inhibitors of neuropeptide release. Paralytic toxicity is due to inhibition at the neuromuscular junction, and this effect has been utilized for treatments of painful dystonias. Pain relief following BoNT muscle injection has been noted to be more significant than muscle weakness and hypothesized to occur because of the inhibition of peripheral neuropeptide release and reduction of peripheral sensitization. Because of this observation, BoNT has been studied as an intra-articular (IA) analgesic for chronic joint pain. In clinical trials, BoNT appears to be effective for nociceptive joint pain. No toxicity has been reported. In preclinical models of joint pain, BoNT is similarly effective. Examination of the dorsal root ganglion (DRG) and the central nervous system has shown that catalytically active BoNT is retrogradely transported by neurons and then transcytosed to afferent synapses in the brain. This suggests that pain relief may also be due to the central effects of the drug. In summary, BoNT appears to be safe and effective for the treatment of chronic joint pain. The long-term effects of IA BoNT are still being determined.


2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.


2014 ◽  
Vol 94 (1) ◽  
pp. 81-140 ◽  
Author(s):  
Emmanuel Bourinet ◽  
Christophe Altier ◽  
Michael E. Hildebrand ◽  
Tuan Trang ◽  
Michael W. Salter ◽  
...  

The detection and processing of painful stimuli in afferent sensory neurons is critically dependent on a wide range of different types of voltage- and ligand-gated ion channels, including sodium, calcium, and TRP channels, to name a few. The functions of these channels include the detection of mechanical and chemical insults, the generation of action potentials and regulation of neuronal firing patterns, the initiation of neurotransmitter release at dorsal horn synapses, and the ensuing activation of spinal cord neurons that project to pain centers in the brain. Long-term changes in ion channel expression and function are thought to contribute to chronic pain states. Many of the channels involved in the afferent pain pathway are permeable to calcium ions, suggesting a role in cell signaling beyond the mere generation of electrical activity. In this article, we provide a broad overview of different calcium-permeable ion channels in the afferent pain pathway and their role in pain pathophysiology.


2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Shigetaka Yoshida

Abstract Klk8 is a tryptic serine protease with limited substrate specificity. Klk8 mRNA is expressed in many developing organs, whereas its expression is confined to limited regions, including the hippocampus, in adults. In the hippocampus, Klk8 is involved in activity-dependent synaptic changes such as long-term potentiation, which was found to be suppressed in Klk8 knockout (KO) mice. Oligodendrocytes only expressed Klk8 mRNA after injury to the central nervous system. The epidermis of the skin is one of the tissues that exhibits a high level of KLK8 expression. Klk8 might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis. Klk8 might thus be involved in tissue development and rearrangement.


1991 ◽  
Vol 275 (1) ◽  
pp. 183-186 ◽  
Author(s):  
M Orford ◽  
D Mazurkiewicz ◽  
G Milligan ◽  
D Saggerson

1. Rats (4 weeks old) were made hypothyroid by treatment with propylthiouracil together with a low-iodine diet for a further period of 4 weeks. Synaptosomal membranes were obtained from six anatomical regions of the brain. 2. The abundances in these membranes of the G-protein alpha-subunits Gi1 alpha, Gi2 alpha and Go alpha were measured by quantitative immunoblotting. 3. Hypothyroidism significantly increased the abundances of all three G-protein subunits in membranes from the cerebral cortex and the striatum. In the medulla oblongata and the hippocampus the abundances of Gi2 alpha and Go alpha were increased significantly. By contrast, in the cerebellum only Go alpha was increased, and in the hypothalamus only Gi2 alpha was increased. 4. It is suggested that this up-regulation of G-protein abundances may modify signalling pathways and may contribute to the functional changes that are observed in the central nervous system in hypothyroidism.


Neurosurgery ◽  
1987 ◽  
Vol 20 (2) ◽  
pp. 335-342 ◽  
Author(s):  
Mark J. Perlow

Abstract Parkinson's disease is an illness with neuropathological and neuroanatomical abnormalities in many areas of the central nervous system. Some clinical manifestations of this illness are correlated with pathological changes in the substantia nigra and with a loss of dopamine in the nigra and striatum. The most effective pharmacological treatments have used agents that either replace the lost dopamine or act as agonists on dopamine receptors. Recent studies in animal models of Parkinson's disease demonstrate that the loss of dopamine and many clinical manifestations of dopamine reduction can be reversed by transplantation of fetal dopamine-containing cells to specific dopamine-depleted areas of the brain. Long term viability of these transplants has also been demonstrated. The author suggests that the transplantation of dopamine neurons, even across species barriers, is a reasonable consideration for the treatment of human Parkinson's disease. This article reviews in detail the results of recent experiments and how the experience in these models might be utilized in determining a transplantation strategy for the treatment of specific clinical aspects of this illness.


Author(s):  
Benjamin M. Greenberg ◽  
Allen Desena

Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory disorder of the central nervous system (CNS) that can be fatal or lead to long-term disability. Various triggers have been identified in children and adults, which presumably cause an autoimmune response targeting myelin. The resulting inflammation causes demyelination and edema of the brain, spinal cord, and optic nerves. Depending on which portion of the CNS is affected, patients will experience a variety of symptoms including weakness, numbness, ataxia, encephalopathy, and seizures. Treatment is currently focused on reducing the amount of inflammation and supportive care.


Author(s):  
Sahib S. Khalsa ◽  
Justin S. Feinstein

A regulatory battle for control ensues in the central nervous system following a mismatch between the current physiological state of an organism as mapped in viscerosensory brain regions and the predicted body state as computed in visceromotor control regions. The discrepancy between the predicted and current body state (i.e. the “somatic error”) signals a need for corrective action, motivating changes in both cognition and behavior. This chapter argues that anxiety disorders are fundamentally driven by somatic errors that fail to be adaptively regulated, leaving the organism in a state of dissonance where the predicted body state is perpetually out of line with the current body state. Repeated failures to quell somatic error can result in long-term changes to interoceptive circuitry within the brain. This chapter explores the neuropsychiatric sequelae that can emerge following chronic allostatic dysregulation of somatic errors and discusses novel therapies that might help to correct this dysregulation.


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