Axonal injury is characterized by an interruption of axonal fibers (Fig. 3.2b) as demonstrable - for example - as a result of a gunshot: the axons will be fragmented (Figs. 8.13b, 9.19). Moreover, axonal injury induces an anterograde (Wallerian) and retrograde degeneration of the injured axons. The terms "anterograde" and "retrograde" refer to the directions of conduction of the nerve impulse along the axon, i.e., the degeneration following focal damage proceeds in a centrifugal or centripetal direction (for review see Brodal 1982).
An interrupted anterograde flow of proteins along the axon can cause the phenomenon of axonal injury. This phenomenon was once demonstrated by H&E stain and by silver staining techniques within 16-24 h after a traumatic event (Strich 1956; Adams et al. 1982). But since the injured axon is selectively characterized by expression of P-amyloid precursor protein (P-APP) (Fig. 4.21d-f; cf. Gentleman et al. 1993; Sherriff et al. 1994), it is now routinely confirmed in 105-180 min (Blumbergs et al. 1995; Oehmichen et al. 1999), in adult brains as well as in infant brains (Reichard et al. 2003). P-APP expression is seen even if the axonal injury is moderate or the axotomy delayed or incomplete (Povlishock 1992). Although axonal injury was long thought to be a morphological correlate of MBI, it is now known to be a non-specific phenomenon also associated with acute intoxication (Nies et al. 2002) or hypoxia/isch-emia (Oehmichen et al. 1999).
In a recent study Graham et al. (2004) evaluated the pattern of P-APP immunoreactivity. The authors identified three different types:
1. A diffuse - multifocal type - in MBI, CO poisoning and hypoglycemia;
2. A type corresponding to the outlines of an infarct or hematoma with evidence of raised intracrani-cal pressure;
3. A mixture of (1) and (2) which was seen in serve MBI.
It is still unclear which events trigger axonal degeneration within the CNS and PNS. Kapoor et al. (2003) suggest a link between nitric oxide (NO) and subsequent molecular events that previously have been indicated as contributors to reversible and irrevers ible axonal injury. Waxman (2003) demonstrates the axonal death cascade induced by hypoxia, ischemia, mechanical trauma, inflammation or NO. The molecular events involving sodium channels and the Na+/Ca2+ exchanger lead to an increase in intracellular calcium, which can provoke axonal degeneration.
Axonal injury of myelinated axons is always accompanied by a demyelinating process, i.e., a loss of myelin, which will be eliminated by mononuclear phagocytes (see: Fig. 9.15b). The sequelae will be a glial scar lacking myelin as demonstrable by Luxol fast blue stain (Fig. 4.22a) or by immunohistochem-istry using an antibody against myelin basic protein (Fig. 4.22b, c).
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