Central Nervous System Summary

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

cell linages like astrocytes have been reported to have an elevated level of HSPs to

Since antibodies are not normally present in the CNS, microglial cells are the main active immune defense. As they are extremely plastic, microglia can adopt different morphologies, which two of the most important are the ramified and the activated one. The highly ramified morphology corresponds to the “resting” microglia, with long branches constantly moving and a small cellular body. The activated microglia presents a small amoeboid cell body with thicker and retracted branches, and it is associated with a pro-inflammatory phenotype. Microglial cells can go through the classical activation by stimulation with LPS and IFN-γ and can produce pro-inflammatory cytokines/mediators such as IL-1β, IL-6, TNF-α, CCL2, ROS, and NO18,19; suggesting that these molecules contribute to dysfunction of neural network in the CNS20. The microglia in this state is termed “M1 microglia”, while “M2 microglia” is used to include the states of both alternative activation21. IL-4 and IL-13 can induce alternative activation,

years later, brain scientists assumed that neurons connected within one another. Glial Cells represented our thoughts and that glia were kind of like stucco and grout holding the house composed. They were well-thought-out as modest insulators for neuron communication. There are some rare kinds of glial cells, but recently scientist’s experts have begun to focus on a more precise brand of glial cell called the 'astrocyte,' as they are rich in the cortex. Technologists have also exposed that astrocytes connect to themselves in the cortex and are also gifted of sending information to neurons. Finally, astrocytes are also the mature stem

So what are neuroglia? The two major components of the central nervous system are neurons and glial cells. Since Rudolf Virchow first observed them in the 1800s, glia were thought to be support cells in the brain. Glia greatly outnumber neurons, forming approximately half the volume of an adult mammalian brain. When early neurophysiologists recorded glia using electrodes, they found only passive membrane currents, so these early researchers assumed that half of the brain was silent (Algulhon, et al., 2008). In the late 1970s, this assumption was challenged. Using florescent imaging, researchers began to observe glial intracellular calcium fluxes, which lead to release of neuroactive substances, called

As shown in Figure 1 (Barker 1991), the neuron is composed of three parts: the dendrite, the cell body, and the axon. The dendrites are structures resembling tree branches that receive signals from other neurons and send them to the cell body. The cell body determines which signals among the many that it gets from the dendrites to send to the axon, which sends signals away from the cell body to other neurons (Herlihy, 2000). The axons are sheathed by a layer of fat known as myelin, which protects the axon and increases the speed at which impulses are carried out. However, myelin is formed differently in the central nervous and peripheral systems. In the central nervous system myelin is created by a type of cell known as oligodendrocytes, while in the peripheral system they are formed by Schwann cells (Hall 1991).

Astrocytes perform a multitude of important functions, such as, in supporting the endothelial cells that form the blood-brain barrier, provide maintenance of extracellular ion balance and play a role in the repair and scarring process of the brain and spinal cord following traumatic injuries. When astrocytes become affected by the build-up of plaque they become unable to provide all of these necessary bodily functions to an individual. The presence of this plaque also makes it more difficult for the BBB to restrict and mediate the substances that pass

On September 2013, the creation of cerebral organoids was achieved. Cerebral organoids are very small samples of brain tissue (Young). The creation of brain tissue with stem cells will provide the treatments for Alzheimer’s, Parkinson’s disease, and Dementia. These treatments may not cure the disease completely, but it could stop the disease from getting worse. It could also take away some of the damage already done. “Anything that might reasonably be called a real brain is going to have to pass more tests than simply being made of brain cells and looking a bit like a brain under a microscope” (Coath). This achievement of brain tissue organs can help researchers explore important questions about brain functions, Parkinson’s, and any other brain disease. Parkinson’s disease is a brain disease that causes for people to not have enough dopamine. Stephen Hawking also agrees with this statement. “Stem cell research is the key to developing cures for degenerative conditions like Parkinson’s and motor neuron disease from which I and many others suffer” (Hawking). With Parkinson’s, there is not enough dopamine produced, and messages are not properly sent to the parts of the brain that control movement and some forms of thinking. This disease targets and kills dopamine-producing nerve cells, or neurons. Scientists do not know what causes this disease, but they do know which cells are involved.

The central nervous system is made up of the brain and the spinal cord (Marieb and Hoehn, 2014), which includes neural tissue in the body (Farley, Johnstone, Hendry and McLafferty, 2014). Homeostasis occurs in the central nervous system, monitoring and responding to change externally and internally (Farley, Johnstone, Hendry and McLafferty, 2014). Memory, behaviour and starting voluntary movements are controlled by the central nervous system (Farley, Johnstone, Hendry and McLafferty, 2014), with the spinal cord providing quick responses to stimuli, aiding homeostasis (Tortora and Derrickson, 2013). Muscular sclerosis is a condition that affects the CNS, the chronic inflammatory disease occurs due to the breakdown of the myelin

Twenty years ago many scientists believed, glial cells were considered minor players in the nervous system; even though they outnumber neurons. Glial was thought to work as passive support cells. Glial cells carried nutrients to and removing wastes from the neurons. While the latter carried out the critical nervous system functions

Microglia serve as the resident innate immune cells of the brain parenchyma which play different roles in adult and developing CNS ranging from immunological surveillance to neurological preservation.17,18 Although microglia are the primary cells involved in innate immunity in the CNS, astrocytes and neurons also take part in immune response.19 Microglia were firstly identified as rod-shaped nucleus containing cells in the brain over one-hundred years ago and were named Staebchenzellen.20 Microglia with the capacity for self-renewal and long-living originate from myeloid progenitors within the yolk sac and migrate to the developing CNS during early embryogenesis. They are different from the cells derived from the bone marrow by haematopoiesis and from the blood circulating cells.21,22 These phagocytes make up approximately 10% of heterogeneous cell population in CNS and trigger both innate and adaptive immunities in neuroinflammation.12,13

The primary defense in the immune system are macrophages. The macrophage population in the CNS comprises of microglia, perivascular macrophages, meningeal macrophages, and choroid plexus macrophages. Microglia comprise around 10% of the cell population in the brain,but the ratio of microglia to neurons varies among different brain regions {Sousa, 2017 #81}. Extensive recent studies have indicated that these cells undergo dynamic alterations in their structure and function during different pathophysiological processes. For this reason, these cells have been classified as ramified microglia (physiological, typical of healthy CNS), dystrophic microglia (deterioration due to age-related processes), and reactive microglia (hypertrophy due to acute injury). Dystrophic microglia play an important role particularly in the context of

Hence, in the present study, the elevated expression of ED-2 in both dorsal and ventral hippocampus accounts for the incidence of alternate activation of macrophages and microglia activation up to the 12th week PDC. A recent study on AD has also shown that the ED-2 positive cells were present in higher density around the compromised blood vessels (Pey et al., 2014) might be indicating the BBB breakdown. This information supports the functional aspect of ED-2 expression in the resolution phase of inflammation (Polfliet et al., 2006) due to infiltration of inflammatory molecules following BBB damage (Perry, 2004). In our previous study (Nagayach et al., 2014a) we reported the astrocytic fragmentation a possible sign for the compromised functioning of the blood brain barrier (Huber et al., 2006) and oxidative stress (Mastrocola et al., 2005) in the brain following diabetes. Considerably, the recorded intense expression of ED-2 was might be a consequence of BBB damage. In addition to this, it might also be possible that the observed intense expression of ED-2 in the diabetic hippocampus (both dorsal and ventral) was aggravated by the activated microglia to further facilitate its role in initiating the cascade of events of the immune system. Similarly, the presence of ED-2

Neuropathic pain is a widespread health[1]. It is a complex disorder that leads to chronic illness. Although considerable progress has been made, the mechanisms of neuropathic pain have not been fully elucidated[2]. Accumulating evidence indicates that neuroinflammatory may play a critical role in the initiation and maintenance of neuropathic pain, which is now considered to be a neuroimmune disorder[3-6]. Researches showed that activation of glial cells (microglia and astrocytes) contributes to central nervous system neuroinflammation and promotes central sensitization, as well as subsequent development and maintenance of neuropathic pain[7-9]. In addition, several studies have shown that inhibiting microglial and astrocytic activation have analgesic effects in neuropathy[10-12]. Whereas, currently available drugs are either insufficiently effective, or produce undesirable side effects[6].

Apart from these classic hallmarks, increasing evidence has demonstrated uncontrolled glial activation and neuroinflammation in AD brain may contribute independently to neural dysfunction and cell death (Akiyama et al., 2000; Wyss-Coray and Mucke, 2002). Robust activation of microglia has been found in and around the area of amyloid plaques in the AD brain, and reactive astrocytes have been shown to form a halo surrounding the amyloid plaques (Itagaki et al., 1989; Ho et al., 2005). Additionally, numerous proinflammatory factors have been reported to be elevated in both patients with AD and transgenic animal models of AD (Griffin et al., 1989; Akiyama et al., 2000; Ruan et al., 2009). Whether alleviation of neuroinflammation will offer therapeutic benefit for AD remains unclear. Epidemiological studies show a possible association between suppression of inflammation and reduced risk for AD (in t’ Veld et al., 2001; Vlad et al., 2008). Therefore, drugs targeting neuroinflammation might provide benefits for the prevention and treatment of this devastating disease. In the central nervous system, microglia and astrocytes are the major type of glial cells, and activation of these cells has been involved in all neurodegenerative diseases (Wyss-Coray and Mucke, 2002). Nevertheless, the diverse physiological functions of glial activation might complicate the interpretation of experimental