The Serration Of Microglial Cells

2010). The neuroinflammation is an early, non-specific immune reaction to tissue damage or pathogen invasion (Lee et al. 2010). Inflammation of the central nervous system (CNS) is characterized by increased glial activation, pro-inflammatory cytokine concentration, blood-brain-barrier permeability, and leukocyte invasion (Lee et al. 2010). Microglia are cells that support and protect neuronal functions (Lee at al. 2010). They act as the first and main form of active immune defense that orchestrate the endogenous immune response of the Central Nervous System. The microglia play a central role in the cellular response to pathological lesions such as Aβ. Aβ can attract and activate microglia, leading to clustering of microglia around Aβ deposits sites in the brain (Lee et al. 2010). Even though microglia have neuroprotective functions, neurotoxic mechanisms which involves continuous activation of microglia and toxic factors are released by microglia, which may lead to neuroinflammation (Lee et al. 2010). Astrocytes (star-shaped glial cells) are the most abundant cells in the brain and are located in the brain and spinal. Astrocytes have various functions such as: biochemical support of endothelial cells of the BBB, supplying nutrients to the nervous tissue, maintenance of extracellular ion balance, and healing the brain and spinal cord following traumatic injury (Lee et al., 2010). Chemokines are released by astrocytes which attract microglia and they further express proinflammatory products, thus increasing neuronal damage in the pathogenesis of AD (Lee et al., 2010). Astrocytes play a critical role in Aß clearance and degradation, and they also provide trophic support to neurons forming a protective barrier between Aß deposits and neurons (Wyss-Coray et al., 2003). Neurons contribute to the production of

Similarly, an increase in the levels of lipid peroxidation was observed in Aβ-induced rat hippocampal cells, confirming previous reports [17]. Enzymatic antioxidants such as SOD, catalase, and GPX act as the cellular antioxidant defense mechanism against free radicals. Since NADPH is required for the regeneration of catalase from its inactive form, catalase activity might be decreased in Aβ induced toxicity due to reduced NADPH levels. In this study, we have reported that Honokiol treatment significantly increased the enzymatic antioxidant activities in APP-CHO cells. In addition, non-enzymatic antioxidants like GSH also exhibited beneficial neuroprotective effects against oxidative stress. GSH is an endogenous nonenzymatic antioxidant that prevents damage to cellular components caused by ROS such as free radicals and peroxides. GSH is oxidized to glutathione disulfide (GSSG) by ROS, thereby causing a reduction in the level of GSH. GR reduces GSSG to GSH via NADPH, which in turn is released by glucose-6-phosphate dehydrogenase [18]. Honokiol treatment upregulated the activity of these antioxidants in APP-CHO cells. In addition to oxidative stress, a strong association between insulin resistance and the development of AD has been demonstrated. Several studies have reported that insulin resistance (IR), an underlying characteristic of type 2 diabetes, is an important risk factor for AD

Inflammation is a reaction of tissues in response to any injury the human or vertebrae sustains. Neuroinflammation is the inflammatory response by the glial cells that are present in the nervous system along with neurons. It is an immune response to pathogen invasion or tissue damage most likely to be caused by Infectious bacteria, Traumatic brain injury (TBI), or toxic metabolites. The nervous system contains neurons and glial cells composed of astrocytes, microglia, oligodendrocytes, ependymal cells in the Central nervous system (CNS), and Schwann cells, satellite cells in Peripheral nervous system (PNS). The glial cells are non-neuronal cells that help to form myelin, maintain homeostasis, provide support for neurons with nutrients, destroy

Diabetes is a long-term metabolic condition characterized by high blood sugar levels. There are three major categories of the disease, type 1 diabetes occurs when the body produces minimal or no insulin, type 2 diabetes is when the body produces either little insulin or the cells are unable to respond to insulin, gestational diabetes mainly occurs during pregnancy. Non-Insulin Dependent Diabetes Mellitus, which is, type 2 diabetes is the most prevalent. The major complication that is caused by Type 2 diabetes is unremitting hyperglycemia, which leads to numerous changes in the body. There are several alterations in cellular, cardiovascular, and nervous functioning, which contribute to complications such as neuropathies and heart

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

Acting in accordance with National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), diabetic neuropathies are family of nerve syndromes affected by diabetes (2009). People with diabetes can be asymptomatic overtime and some can have notable signs with radicular symptoms in the upper and lower extremities (NIDDK, 2009), Moreover, can affect even the digestive, cardiac, and reproductive system in serious conditions (NIDDK, 2009). In fact, based on academic literatures, about two thirds of patients with diabetes have medical or subclinical pathology of nerve (Bansal, Kalita, & Mistra, 2006). The occurrence of neuropathy amplified from approximately 7 percent to 50 percent on admittance at 25 years in consequence (Bansal, Kalita, & Mistra, 2006).

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

In general, each neuron releases a single type of neurotransmitter. Neurons that release the neurotransmitter acetylcholine are called cholinergic neurons and degeneration of cholinergic neurons in the brain are associated with Alzheimer’s (Sherwood). Drugs classified as short-term cholinesterase inhibitors are used to treat Alzheimer’s because the drugs prolong the effect of acetylcholine. There are special cells called microglia that are associated with Alzheimer’s disease as well. Microglia are immune defense cells in the CNS (central nervous system) or brain and spinal cord. The remove foreign and degenerate material in the CNS. Overactive microglia appear to be involved in a variety of inflammation-related disorders like Alzheimer’s (Sherwood). Inflammation is triggered by the body’s immune system and is a factor that plays in the progression of the disease (Alzheimer’s Disease & Dementia).

The hippocampus has a region (CA1), which is more vulnerable and sensitive to the hypoxia that leads to inflammatory responses (COX-2, TNF-a),2 which can bring about endothelial dysfunctions,3 disturbances of the cerebrovascular blood flow,3 and consequently neuronal cell death.3 In addition, it provokes oxidative stress and nitric oxide synthase (iNOS).2

At adult normal physiological condition, microglial display surveillance or so-called ‘resting’ phenotypes gauged by small cell body with extensively ramifying processes that actively surveying the CNS microenvironment. In this steady state, the turnover processes is primarily confined and well-maintained through local self-renewal of the long-lived resident microglial. Anomalies in the CNS such as infections, tissues damage, and accumulation of abnormal protein or biochemical can trigger microglial activation and in turn cause inflammation in CNS. Different from steady state, inflammatory condition may have disrupted the integrity of blood brain barrier and allowed recruitment of circulating myeloid cells and promotes their differentiation into microglial with more potent inflammatory properties and resulting heterogeneity of microglial . Activated microglial rapidly proliferate undergo phenotypic transition where they will exit from the ‘resting’ or ‘surveying’ form and mounted inflammatory effectors functions. Evidences showed that activated microglial capable of upregulated its phagocytose properties and secrete of inflammatory mediators chemokines, cytokines, nitrite, reactive oxygen species, and free radicals to execute repair

Human central nervous system (CNS) is composed of neuron and glial cell ( astrocytes, oligodendrocytes, microglia) which act as structural support of brain and also contribute for formation of synapse. Microglia comprises 10% of the adult CNS. When there is tissue injury, trauma or pathogen, ramified microglia will undergo biochemical changes and turned into an activated microglia. The cell body

Globally, The number of patients with diabetes is increasing rapidly. By the year 2035, the number of people with diabetes worldwide is expected to rise to 592 million (IDF ATLAS 20131). Diabetic peripheral neuropathy (DPN) is a common microvascular complication of diabetes and a leading cause to amputations in hospitals (Boulton 20052). The prevalence of DPN is estimated to be 50-60% (Sandireddy R 20143). The pain associated with DPN can affect the patient quality of life (QOL). It affects their sleep, lifestyle, work and even can cause or be associated with depression (Jensen MP 20074). It is not well understood whether the mechanism behind peripheral neuropathy with diabetes is hyperglycemia or other insulting pathophysiological mechanism like proinflamatory immune mediators (Herder C 20135, Goh S-Y 20086). One of the possible mechanisms is the demyelination of the small C fiber, this is the leading cause behind the pain sensation with

Microglia, macrophages, mast cells, blood monocytes, dendritic cells, and neutrophils are rapidly activated, as well as extracellular ATP and neurotransmitters (Iadecola & Anrather, 2011). “Thrombosis and hypoxia trigger an intravascular inflammatory cascade, which is further augmented by the innate immune response to cellular damage occurring in the parenchyma” (Kamel & Iadecola 2012). Activation of the innate immune system triggers the adaptive immune system to prepare for brain antigens, but does not have an effect on the immediate recovery of am ischemic stroke. Since the blood brain barrier is changed, cells of the immune system have direct access to the brain parenchyma and local autoimmunity contributes to lesion formation. Immunodepression is common in post-ischemic stroke patients. “The immune system participates in the brain damage produced by ischemia, and the damaged brain, in turn, exerts an immunosuppressive effect that promotes fatal infections” (Iadecola & Anrather,

The sub-acute phase continues from the acute phase and characterized by new events such as formation of free radicals, delayed calcium influx, apoptotic cell death, inflammatory response, central cavitation initiation, and astroglial scar initiation (28). Neutrophils are the first immune cells to respond/arrive at injury, removing microbial intruders and tissue debris. Neutrophils release protease metalloproteinase, ROS, TNF-α, IFN-γ, IL-1, 8, 12 and other pro-inflammatory factors to activate other inflammatory and glial cells (29, 30). While initially beneficial, neutrophil persistence significantly increases damage through continuous production of pro-inflammatory cytokines and proteolytic enzymes (31). Therefore, neutrophil activation is limited to a couple days, and is contained to the sub-acute phase. Microglia and macrophages become active in response to neutrophils and the injury, also releasing numerous

Hyperglycemia is known to adversely affect peripheral nerve structure and function in younger (3–6 months) but not in older rats. Physical and functional damage to peripheral nerves associated with diabetes is related to increased activity of the polyol pathway . The polyol pathway is a minor pathway of glucose metabolism that increases the intracellular content of the polyol sorbitol in response to increased extracellular glucose concentrations.