Increased expression of growth-associated protein 43 immunoreactivity in axons following compression trauma to rat spinal cord

Abstract

Growth-associated protein 43 (GAP43) is one compound used to indicate growth of axonal endings during development and regeneration, particularly of peripheral neurons. Using immunohistochemistry, we have studied the expression of GAP43 in the spinal cord of rats subjected to mild, moderate or severe compression injury and used neurofilament immunostaining to demonstrate axonal injuries. Samples removed from the compressed T8-9, the cranial T7 and the caudal T10 segments were studied at 4 h, 24 h, 4 days and 9 days after injury. Control rats showed a moderate immunostaining of neurons in dorsal root ganglia, weak staining of ventral motor neurons and, with the exception of the corticospinal tracts, a weak staining in some axons of the longitudinal tracts of the cord. Injury in the compressed region led to increased GAP43 immunoreactivity in axons of normal and expanded size. This occurred particularly 1-4 days after injury and normalized 9 days thereafter. More marked immunostaining was present in the cranial and caudal segments. The corticospinal tracts never showed such staining. The increase of GAP43 immunostaining is presumably caused by disturbed axonal transport from neurons with the capacity to synthesize and transport the GAP43 antigen. Transported material may thus be available for regeneration of axons, but this source of material may vary between different classes of axons within the cord.

GM-CSF inhibits glial scar formation and shows long-term protective effect after spinal cord injury

“…We do not completely exclude the possibility of neurotrophic action of GM-CSF, but it is not likely that it could directly enhance axonal regeneration. Transient increase in GAP-43 expression within 1 week after SCI was observed in neurons around the lesion area of rat spinal cord [29][30][31], which suggest possible role(s) of GAP-43 in the in the compensatory and repair mechanisms after SCI. However, the expression of GAP-43 alone does not appear to be sufficient for axonal regeneration [32], and we could observe increase of its expression by GM-CSF only after 3 weeks after SCI but not at early time of 1 week (data not shown).…”

Increased expression and colocalization of GAP43 and CASP3 after brain ischemic lesion in mouse

“…Other genes involved in this process are mostly linked to formation of neurofilaments, microtubules or myelin. In rodents affected by tMCAO, GAP43 is present during the early phase in the focus of ischemic lesion, followed by expression in penumbra [18]. This suggested an early role for GAP43 in the rescue and regeneration of tissue.…”

“…Adult cortex in mammals responds to injury with axonal sprouting, with GAP43 being one of the key players in the outgrowth of new axons [7][8][9]18]. Other genes involved in this process are mostly linked to formation of neurofilaments, microtubules or myelin.…”

Does β-amyloid plaque formation cause structural injury to neuronal processes?

“…Following axonal injury a regenerative sprouting response is observed both in vitro and in vivo that is characterised by the presence of fine calibre neurites expressing GAP43 and other proteins associated with neurite growth at the site of injury (Li et al, 1996;Christman et al, 1997;Hou et al, 1998;Dickson et al, 2000;King et al, 2001;Chuckowree and Vickers, 2003;Chung et al, 2003). The DNs in AD also share similarities with these regenerative or sprouting axons, albeit with aberrant morphology.…”

“…In this regard, the growth-associated protein, GAP43, has been widely used as a marker for neuritic outgrowth, including the regeneration of axons following injury Li et al, 1996;Christman et al, 1997;Hou et al, 1998;Dickson et al, 2000;King et al, 2001). Sprouting neurites containing GAP43 and NF triplet protein are present following transection of axonal bundles in vitro King et al, 2001;Chuckowree and Vickers, 2003) and GAP43 mRNA is upregualted in neurons in Clarke's nucleus following axotomy in vivo, even if they are destined to degenerate (Schmitt et al, 1999).…”