Microglial and Neurological Disorder

There are four different patterns of inflammation in the white matter that is associated with individuals with multiple sclerosis (Lassmann et. al. 2007).The first pattern of inflammation is associated with the demyelination caused by macrophage activity. This pattern of inflammation is characterized by perivascular demyelination with radial expansion and extensive remyelination. The second pattern of inflammation demyelination is associated with antibody and complement activity. The lesions exhibited in this pattern are similar to lesions that occur in the first pattern except that the active demyelination sites demonstrate additional deposition of immunoglobulin (Ig) and activated complement in pattern 2. Immunoglobulins are antibodies that

(Okabe, 2012). Microglia are the immune system in the central nervous system (CNS), and act by responding to any injuries and diseases by proliferating, removing cellular debris, and activating a neuroinflammatory response (Lioy et al, 2011). Even in their dormant state, microglia extensively and endlessly scrutinize their cellular surroundings which means that microglia are always in close interaction with their nearby astrocytes and neurons (Noda, 2015). Recently, scientists have hypothesized that in RTT, microglia causes a non-cell autonomous effect in which only genotypically mutant cells exhibit the mutant phenotype (Maezawa & Jin,

The exact cause of MS is unknown. However, its pathogenesis is associated with irregular immune responses against CNS antigens, interference of the blood-brain barrier (BBB) and trans endothelial migration of activated leukocytes, as well as chemokines and cytokines, from peripheral circulation to the CNS. In active disease, there appears to be ongoing inflammatory as well as neurodegenerative processes within the CNS atmosphere. The triggering event for the first attack of MS remains projected. It is assumed that genetic and environmental factors are involved in the progress of MS. (Borazanci, 2009, p. 2)

Sepsis associated encephalopathy (SAE) is a complex and potentially serious consequence of sepsis appearing in many clinical forms. SAE is no more than the manifestation of a sinister cascade of damaging molecular interactions that can potentially lead to irreversible neurocognitive dysfunction. The pathophysiology of SAE is unknown but recent animal studies have shed some important information about some of the responsible molecular mechanisms and potential sites for future interventions. These pre-clinical studies have demonstrated the role of classic inflammatory factors that lead to blood-brain barrier dysfunction, astrocyte dysfunction, apoptosis, and neuronal death. Further studies are warranted to enhance our understanding of the process

Through inflammation and destruction of the myelin sheath covering nerves, irreversible damage slows, redirects, or stops nerve impulses. This is due to the fact that nervous tissue cannot repair itself resulting in plaques also referred to as MS lesions being left behind. Demyelination can occur in grey or white matter of the nervous system with wide reaching affects due to the immune system attacking the nervous system systemically as opposed to being confined to a small area. Huether, S and McCance, K (2012) found that MS is usually triggered in genetically predisposed individuals by a viral infection, traumatic injury, or

Shrinkage in parts of the brain such as the cortex and hippocampus, affects functions such as remembering, planning and even thinking. The remaining tissue contains plaque, abnormal clusters of protein fragments, between surviving nerve cells. This plague can block cell-to-cell signaling at synapses and activate immune system cells that trigger inflammation while devouring disabled cells. The dead and dying nerve cells contains tangles, which are made up of twisted strands of another protein. Tangles destroy a vital cell transport made of proteins, which block nutrients and other essential supplies from reaching cells, which then die. The progression of Alzheimer’s disease follows the spreading of plaque and tangles throughout the brain. The escalation damage areas of the brain that involve speaking and understanding speech and also the sense of where a body is in relation to surrounding objects. In severe cases of Alzheimer’s, where the cortex is intensively damaged, the brain shrinks so dramatically due to widespread cell death that individuals lose the ability to communicate, recognize loved ones, and care for

Specially, the exposure of brain parenchyma to blood circulation and the release of danger-associated molecule signals from damaged cells that initiate epileptogenic inflammatory cascades. In chronic neuro-inflammation, astrocytes and microglial cells act in a deleterious manner contributing in sustained release of pro-inflammatory cytokines, chemokines (such as S100B, interleukins [i.e., IL-1B,IL-6], tumor necrosis factor-alpha (TNF-a), interferon-y-inducible protein-10 (IP-10)), transforming growth factor (TGF) and proteases. The sensitive reactivation process and the inducible overproduction of pro-inflammatory mediators make astrocyte a very important contributor to the neuro-inflammation in the early onset of brain

Microglia are resident immune cells in the CNS, separated from many blood-borne molecules by the BBB. However, evidence suggests that BBB endothelial cells either act as transporters of hormones and cytokines across the BBB or as classic receptor sites, possibly reacting to signals in the blood by secreting other signals into the CNS.8 By these mechanisms, microglia can become activated in response to inflammatory stimulation such as the cytokines and hormones that cross the BBB.9 Also, metabolic disease frequently leads to compromise of the BBB, providing greater access for circulating molecules to the CNS. It is not clear whether metabolic disease causes microglia to weaken the BBB, or whether the BBB is weakened first, with microglia then

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the nerve and nerve fibers of the central nervous system (Ringold, Lynm, & Glass, 2006). It results in the loss and damage of myelin, the insulator of nerve fibers, thus affecting the conduction of nerve signals within the brain and spinal cord. This damage to the central nervous system (CNS) leads to an impairment in sensory, cognitive, and motor functions of the body. The cause of multiple sclerosis is still unknown, however, it is known that environmental, genetic, and viral factors play a role in the spread and diagnosis of this disease. This essay will examine the likelihood of the Epstein-Barr virus as an indicator to the development of multiple sclerosis.

When looking at lesion borders, the chronic plaques have clearer borders than the acute plaque. In these chronic plaques, there is a division into two forms to divide between “temporal evolution from active destruction at the edge of the lesion to a “burned out” lesion devoid of active inflammatory destruction.” 4 On the borders of chronic active plaque, there are active microglia and macrophages along with reactive astrocytes. Remyelination is not common and oligodendrocytes are completely lost with a reduction in the density of the axon.

Multiple Sclerosis (M.S) is a chronic autoimmune, inflammatory disease of the Central Nervous System (CNS) that leads to a variety of disabilities, including: asthenia, lack of coordination, abnormal vision, cognitive changes, and sexual and urinary dysfunction(1). M.S pathogenesis involves a complex process of the activity of macrophages and micro-glial cells that leads to differentiation of specific neural Th1 lymphocytes (Myelin auto reactive T-Cells) and secretion of pro-inflammatory cytokines in the CNS. Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease, characterized by inflammation of central nervous system (CNS) injury. This disease is an animal model of multiple sclerosis in human (2). In EAE, CD4+ lymphocytes call macrophages to the central nervous system, subsequently they are activated against microglia cells, which lead to demyelination of neurons (3, 4). EAE can be induced by injection of central nervous system proteins, such as basic myelin proteolipid protein derived from CNS proteins, to animals such as monkeys, pigs, rats and mice (5, 6). Recently, the role of Th2 cytokines in therapy and control of EAE as a potential treatment for M.S has been accepted. Following information suggest that immune modulators, especially those that lead to suppress Th2 environment, can be potential treatments for M.S(3). Many studies have shown that M.S is a Th1 lymphocyte-dependent autoimmune disease. There have been significant

Researchers from the University of Wollongong in Australia have found a link between the ATP-binding transporter A7 (ABCA7) and the regulation in the risk of Alzheimer’s disease. ABCA7 helps to clear out Aβ (amyloid beta) from the brain. Aβs can group together and block cell-to-cell signaling at synapses. The evidence in human and mouse trials have shown that ABAC7 has a role in the regulation of Alzheimer’s treatment and risk. ABCA7 has been found to be in high amounts amongst microglia in the brain and directly regulates phagocytosis. Further testing was done to determine what the exact link is between this transporter and Alzheimer’s disease.

Emerging evidence demonstrates neuroinflammation as a crucial pathophysiology of AD, specifically impacted by microglia and astroglia. 3 The microglia are distributed evenly across the brain and are activated by protein aggregation and neuronal cell death. 3 Specifically related to AD, the two chief proteins involved are amyloid-B and tau.3 An accumulation of microglia around amyloid-B plaques has been documented in post-mortem human brains and in animal models with AD.3 Research has yet to clearly determine if microglial activation plays a beneficial or detrimental role in the progression of AD..3 Some reports suggest that microglia are attracted to

In the primary research article given to us titled “Complement and microglia mediate early synapse loss in Alzheimer mouse models” it talks about a study about the causes of Alzheimer’s disease in mice. Alzheimer’s is believed to be caused by multiple factors. One of these are called complement proteins. According to the University of Washington, they are a group of around 20 different proteins that assist with fighting infections. Complement proteins are found in our blood and they assist in fighting infections in various ways. Some of these proteins bind to the surface of a pathogen were antibodies are already present to make sure that the pathogen is phagocytized. Other proteins cause histamines to be released or act as a signal to draw phagocytes to the pathogens. According to the National Center for Biotechnology Information, C3 is a type of complement protein that is vital to the activation of the entire complement system. C1q is another complement protein that it is a piece of the classical pathway for the activation of the complement system. According to the The Green Lab at the University of California Irvine, macroglia are the immune cells of the central nervous system. Their functions include removing bacteria and unwanted materials from the brain. In order to combat neurological damage and inflammations they have to be activated first. According to the Alzheimer 's Association, Alzheimer’s is a disease that causes a steady decline in brain functions such as

The over the counter medication once known only for its ability of easing aches and pains or fighting off fever and inflammation is proving itself to be quite the miracle drug. Aspirin has become part of the protocol for stroke victims as a preventative measure due to its neuro-protective benefits. Stroke can cause lesions in cerebral white matter, which may result in cognitive impairments such as deficits in learning and memory. White matter lesions (WML) have also been linked to increasing the risk of post-stroke dementia. Cerebral white matter damage has been widely overlooked. Comprised of oligodendrocytes that form the insulating myelin in the CNS, white matter is evidentially just as vulnerable to ischemia as gray matter.