Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle

Mitochondrial Aging and Metabolism: The Importance of a Good Relationship in the Central Nervous System

The mitochondrial theory of aging suggests that mitochondria have a decrease in production capacity of adenosine triphosphate (ATP). The question may seem trivial, but it becomes more complex when considering that dysfunctional mitochondria can be eliminated by lysosomal digestion and that cell with dysfunctional mitochondria can undergo the process of apoptosis. In organs with regenerative capacity, like the liver, cell proliferation can almost completely hide mitochondrial dysfunction. However, evidence indicates selective damage in mitochondria during aging, and so the mitochondrial aging theory is gaining recognition and respect. There is solid evidence that accumulated DNA damage in mitochondria is a cause directly related to metabolic disorders such as diabetes and degenerative disorders such as Alzheimer’s disease. The central nervous system is particularly susceptible to oxidative damage due to several factors, among which are its high oxygen consumption, its dependence on aerobic carbohydrate metabolism, and its complex composition of membrane lipids. Free radicals are generated at many cell sites, and the mitochondrial respiratory chain is one of the main sources. While many studies have been conducted in experimental animal models, the results are relevant because at least some of their interventions suggest a directing aim at reducing the effects of aging

Gut-Brain Axis: Role of Microbiota in Parkinson’s Disease and Multiple Sclerosis

It has recently been discovered that the digestive tract is lined with about 100 million nerve cells; the digestive tract has been baptized, metaphorically speaking, as “the second brain,” which contains a multitude of neurotransmitters, viruses, and bacteria that help regulate our emotional state. This second brain, known as the enteric nervous system, is a unique anatomical unit that extends from the esophagus to the anus. Like the nervous system, it produces a whole series of psychoactive substances, such as serotonin, dopamine, and opioids for pain, and synthesizes benzodiazepines. In it, we find the microbiota: a set of microorganisms (viruses and bacteria). Together with the brain, the microbiota directly influences mood, character, or sleep. Knowledge about the possible relationship of the microbiota with frequent neurological diseases is still just beginning. Recently, possible changes in the microbiota have been linked to the onset of Parkinson’s disease (PD). Also, today, we know that there are differences between the microbiota of healthy people and people with multiple sclerosis and that these differences have also been related to the disease and its evolution

From Probiotics to Psychobiotics: Live Beneficial Bacteria Which Act on the Brain-Gut Axis

There is an important relationship between probiotics, psychobiotics and cognitive and behavioral processes, which include neurological, metabolic, hormonal and immunological signaling pathways; the alteration in these systems may cause alterations in behavior (mood) and cognitive level (learning and memory). Psychobiotics have been considered key elements in affective disorders and the immune system, in addition to their effect encompassing the regulation of neuroimmune regulation and control axes (the hypothalamic-pituitary-adrenal axis or HPA, the sympathetic-adrenal-medullary axis or SAM and the inflammatory reflex) in diseases of the nervous system. The aim of this review is to summarize the recent findings about psychobiotics, the brain-gut axis and the immune system. The review focuses on a very new and interesting field that relates the microbiota of the intestine with diseases of the nervous system and its possible treatment, in neuroimmunomodulation area. Indeed, although probiotic bacteria will be concentrated after ingestion, mainly in the intestinal epithelium (where they provide the host with essential nutrients and modulation of the immune system), they may also produce neuroactive substances which act on the brain-gut axis

Psycho-Neuro-Endocrine-Immunology: A Role for Melatonin in This New Paradigm

Psychoneuroendocrinoimmunology is the area of study of the intimate relationship between immune, physical, emotional, and psychological aspects. This new way of studying the human body and its diseases was initiated in the last century’s first decades. However, the molecules that participate in the communication between the immune, endocrine, and neurological systems are still being discovered. This paper aims to describe the development of psychoneuroendocrinoimmunology, its scopes, limitations in actual medicine, and the extent of melatonin within it