TY  - JOUR
AU  - Büki, András
AU  - Povlishock, JT
TI  - All roads lead to disconnection?--traumatic axonal injury revisited
JF  - ACTA NEUROCHIRURGICA
J2  - ACTA NEUROCHIR
VL  - 148
PY  - 2006
IS  - 2
SP  - 181
EP  - 193
PG  - 13
SN  - 0001-6268
DO  - 10.1007/s00701-005-0674-4
UR  - https://m2.mtmt.hu/api/publication/1251083
ID  - 1251083
N1  - Funding Agency and Grant Number: FIC NIH HHS [1-R03-TW0131302A1] Funding Source: Medline; NINDS NIH HHS [NS20193] Funding Source: Medline
AB  - Traumatic brain injury (TBI) evokes widespread/diffuse axonal injury (TAI)
significantly contributing to its morbidity and mortality. While classic theories
suggest that traumatically injured axons are mechanically torn at the moment of
injury, studies in the last two decades have not supported this premise in the
majority of injured axons. Rather, current thought considers TAI a progressive
process evoked by the tensile forces of injury, gradually evolving from focal
axonal alteration to ultimate disconnection. Recent observations have
demonstrated that traumatically induced focal axolemmal permeability leads to
local influx of Ca2+ with the subsequent activation of the cysteine proteases,
calpain and caspase, that then play a pivotal role in the ensuing pathogenesis of
TAI via proteolytic digestion of brain spectrin, a major constituent of the
subaxolemmal cytoskeletal network, the "membrane skeleton". In this pathological 
progression this local Ca2+ overloading with the activation of calpains also
initiates mitochondrial injury that results in the release of cytochrome-c, with 
the activation of caspase. Both the activated calpain and caspases then
participate in the degradation of the local axonal cytoskeleton causing local
axonal failure and disconnection. In this review, we summarize contemporary
thought on the pathogenesis of TAI, while discussing the potential diversity of
pathological processes observed within various injured fiber types. The
anterograde and retrograde consequences of TAI are also considered together with 
a discussion of various experimental therapeutic approaches capable of
attenuating TAI.
LA  - English
DB  - MTMT
ER  -