Signs Of Inflammations

Neuroinflammation is viewed as a process that occurs in the CNS and that involves primarily glial responses (1). It does not reproduce the classical characteristics of peripheral inflammation. The term neuroinflammation, apparently not used prior to 1995, is associated with chronic CNS inflammation. It is now considered to be an innate immune response in the brain and is implicated in many chronic unremitting neurodegenerative disorders associated with activated glial cells (1). The complex interactions and feedback loops between glia and neuronal cells make it difficult to establish simple linear cause and effect cascades in these disorders. In this chapter we discuss two of the mechanisms, oxida-tive stress and UPS dysfunction, that can mediate the detrimental aspect of neuroinflammation.

2. WHAT IS INFLAMMATION?

Inflammation is the body's natural response to a variety of insults ranging from infection by bacteria or viruses to injury by chemical or physical agents. Inflammation is a double-edged sword that can benefit or harm the host: it is an extremely important survival tool in the body's defense system, but prolonged or unregulated inflammation can cease to be a beneficial event contributing to the pathology of many diseases. For example, chronic peripheral inflammation is known to be a major cause of asthma, chronic hepatitis, lupus and rheumatoid arthritis. More recently, chronic inflammation of the CNS has been implicated in various neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In addition, acute CNS inflammation has been implicated as a secondary injury mechanism following ischemia and stroke.

Inflammation was already recognized in ancient Egyptian times as described in the Smith Papyrus circa 1650 BC (Figure 1). Later on, the Roman Cornelius Celsius (circa AD 25) was the first to define inflammation as a process characterized by four cardinal signs readily visible on the body surface: heat, redness, swelling and pain (Figure 2). A fifth cardinal sign of inflammation, loss of function, was added by the famous 19th century German pathologist Rudolf Virchow (Figure 2). Following pro-inflammatory events, tissues release chemical signals of infection or injury/damage including vasoactive and chemotactic mediators that contribute to the five cardinal signs of inflammation. Heat and redness at the site of injury are caused by a rise in blood flow, swelling by increased vascular permeability, pain by stimulation of nerve endings and loss of function by destruction of the tissue.

The three major functions of inflammation are (1) to eliminate the source of the insult to prevent its spread, (2) to prepare the injured site for repair and (3) to restore tissue homeostasis. While the inflammatory response is crucial for containing infection and delivering cellular and humoral components of the body's defense systems to the site of injury or infection, an excessive or over-long period of inflammation can be problematical. Resolution of inflammation (anti-inflammatory response) is an active process controlled by

Figure 1. The hieroglyph reads from right to left. The bar is a phonetic "sh"; the two falcons are each a phonetic "m" and the half circle (a loaf of bread) is phonetically "t". The far left item is a flaming brazier with smoke curling up and down - something hot. All together the word sounded something like "she-memet" and was the earliest description of inflammation, [from: http://rdh.c.home.att.net/pdf/ inflamm.pdf].

Figure 1. The hieroglyph reads from right to left. The bar is a phonetic "sh"; the two falcons are each a phonetic "m" and the half circle (a loaf of bread) is phonetically "t". The far left item is a flaming brazier with smoke curling up and down - something hot. All together the word sounded something like "she-memet" and was the earliest description of inflammation, [from: http://rdh.c.home.att.net/pdf/ inflamm.pdf].

Mediators Inflamm

Figure 2. Left: CARDINAL SIGNS OF INFLAMMATION: heat, redness, swelling, pain and loss of function. Reproduced from (2) with permission from Macmillan Magazines Ltd. Right: Cornelius Celsius (top) and Rudolf Virchow (bottom), [from: http://rdh.c.home.att.net/pdf/inflamm.pdf].

Figure 2. Left: CARDINAL SIGNS OF INFLAMMATION: heat, redness, swelling, pain and loss of function. Reproduced from (2) with permission from Macmillan Magazines Ltd. Right: Cornelius Celsius (top) and Rudolf Virchow (bottom), [from: http://rdh.c.home.att.net/pdf/inflamm.pdf].

endogenous mediators that suppress pro-inflammatory gene expression and cell trafficking and induce inflammatory-cell apoptosis and phagocytosis. An optimal balance between pro- and anti-inflammatory responses is required to prevent the highly detrimental effects of extensive, prolonged or unregulated inflammation.

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