Activated microglia

A small amount of AP antibody reaches the brain, binds to A(3 peptides, promotes the disassembly of fibrils, and, via the Fc antibody domain, encourages activated microglia to enter the affected region and remove A(3 [86] and/or... 

FIGURE 57-6 Central sensitization of dorsal horn neurons and a loss of inhibition after nerve injury result in altered processing of sensory input. ATP activates microglia through the P2X4 receptor. The resulting release of cytokines contributes to the development of pain through a mechanism of action that is, as yet, unknown. 

A recent study found that cortical peripheral benzodiazepine receptors, as assessed with PET and [ C]PK11195, were increased by 30-40% in patients with AD when compared with healthy controls. This suggests active inflammatory processes in AD since PK11195 binds to activated microglia [72]. Several F-labeled tracers of the peripheral benzodiazepine receptor have been developed, and [i8p]PK14105 [73] and [i8p]FEDAA1106 [74] are the most well characterized. However, no reports have been published on the use of either of the two radiotracers in AD. The molecular structures of F-labeled tracers for the peripheral benzodiazepine receptor are shown in Fig. 5. 

Vallat-Decouvelaere A. V., Chretien F., Gras G., Le Pavec G., Dormont D., and Gray F. (2003). Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia J. Neuropathol. Exp. Neurol. 62 475 185. 

Qin L., Liu Y., Wang T., Wei S. J., Block M. L., Wilson B., Liu B., and Hong J. S. (2004). NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J. Biol. Chem. 279 1415-1421. 

Like spinal cord trauma, traumatic head injury consists of a primary injury, attributable to the mechanical insult itself, and a secondary injury, attributable to the series of systemic and local neurochemical changes that occur in brain after the initial traumatic insult (Klussmann and Martin-Villalba, 2005). The primary injury causes a rapid deformation of brain tissues, leading to rupture of neural cell membranes, release of intracellular contents, and disruption of blood flow and breakdown of the blood-brain barrier. In contrast, secondary injury to the brain tissue includes many neurochemical alterations such as release of cytokines, glial cell reactions involving both activated microglia and astroglia, and demyelination... 

Ananth C., Gopalakrishnakone P., and Kaur C. (2003b). Induction of inducible nitric oxide synthase expression in activated microglia following domoic acid (DA)-induced neurotoxicity in the rat hippocampus. Neurosci. Lett. 338 49-52. 

Noradrenergic depletion in AD transgenic animals showed an increase in the plaque number and plaque area as well as to an increase in the number of activated microglia and astrocytes (Heneka et al., 2006) (Kalinin et al., 2007). 

Fig. 1. Peripheral and central mechanism of neuropathic pain caused by vincristine. The upper diagram shows the effect of vincristine on the peripheral nervous system (comprising Schwann cells and the dorsal root ganglion (DRG)) and the involvement of interleukin (IL)-6 derived from infiltrating macrophages in neuropathic pain caused by vincristine. The lower diagram shows the effect of vincristine on the central nervous system, and the involvement of tumor necrosis factor-a (TNF-a) derived from activated microglia and astrocytes in neuropathic pain caused by vincristine.

Hains, B. C., and Waxman, S. G. (2006). Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J. Neurosci. 26, 4308—4317. 

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