Microglial Response in Cortical MS Lesions

The resident immune cells of the CNS are the microglia, which monitor pathological changes locally and also at sites distant to their location (Gonzalez-Scarano and Baltuch, 1999; Streit et al., 1999). In cortical MS lesions a striking association between microglia and neurons was identified (Peterson et al., 2001). Double-labeling confocal microscopy

Figure 9 Neuronal pathology in cortical lesions. Nonphosphorylated neurofilament-positive ovoids are abundant in cortical lesions (A, B, green). Confocal microscopy confirmed most of these ovoids as terminal ends of neurites (A, arrowheads) and some as en passant swellings (A, arrows). Some ovoids close to neuronal perikarya could be identified as axonal (B, arrowhead) or dendritic (not shown). Microglial (red) targeting of neuronal perikarya and processes (green) (C, D). Confocal microscopy detected ferritin-positive microglia with elongated shapes ensheathing neurites (C, arrowheads). More stellate-shaped microglia were detected in close apposition to neuronal perikarya and extending processes to and around neurofilament-positive neurites (D, arrows). High magnification image of microglial process (red, arrowhead) ensheathing a branch of an apical dendrite (green) (inset). N = neuron. (Reproduced from Peterson et al., 2001, with permission.)

Figure 9 Neuronal pathology in cortical lesions. Nonphosphorylated neurofilament-positive ovoids are abundant in cortical lesions (A, B, green). Confocal microscopy confirmed most of these ovoids as terminal ends of neurites (A, arrowheads) and some as en passant swellings (A, arrows). Some ovoids close to neuronal perikarya could be identified as axonal (B, arrowhead) or dendritic (not shown). Microglial (red) targeting of neuronal perikarya and processes (green) (C, D). Confocal microscopy detected ferritin-positive microglia with elongated shapes ensheathing neurites (C, arrowheads). More stellate-shaped microglia were detected in close apposition to neuronal perikarya and extending processes to and around neurofilament-positive neurites (D, arrows). High magnification image of microglial process (red, arrowhead) ensheathing a branch of an apical dendrite (green) (inset). N = neuron. (Reproduced from Peterson et al., 2001, with permission.)

detected elongated microglia oriented perpendicular to the pial surface, closely apposed, and ensheathing apical den-drites and axons in active and chronic active cortical lesions (Fig. 9C, D). In addition, other more ramified stellate-shaped microglia often extended processes to neuronal perikarya and ensheathed dendrites or axons (Fig. 9D). Unlike microglia/macrophages in white matter lesions which often apposed the terminal ends of transected axons (Trapp et al., 1998) microglia in cortical lesions did not consistently associate with the terminal ends of transected neu-rites in the cortical lesions (Fig. 9C).

The targeting of neurons and neuronal processes by microglia is suggestive of the process of synaptic stripping.

Microglia in cortical lesions morphologically resemble microglia in an animal model of synaptic stripping (Blinzinger and Kreutzberg, 1968; Graeber etal., 1988). After distal regions of the facial nerve are transected, microglia become activated and target neurons of the affected VII cranial nerve nucleus within a day. By electron microscopy, the microglial processes were detected separating presynaptic and postsynaptic terminals (Blinzinger and Kreutzberg, 1968). Whether microglia in cortical lesions actively target synaptic terminals remains to be determined. It is unknown whether this association between microglia and neurons is destructive or protective. It is likely that the microglia are targeting neurons already functionally impaired. For example, in

Alzheimer's disease (AD), activated microglia are associated with damaged neurites and neuronal loss (Haga et al., 1989; McGeer et al., 1992; Mochizuki et al., 1996). Some of the most promising AD therapeutics are anti-inflammatory therapies targeting activated microglia (Breitner, 1996; Combs et al., 2000). Thus, similar anti-inflammatory therapies, which reduce microglial activation in the cerebral cortex, may benefit patients with MS.

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Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.

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