Recent findings have led to changes in the traditional concept of nerv
e recovery, including the realization that injured nerves, like any ot
her injured tissue, need the assistance of blood-derived cells and fac
tors in order to heal. We show that factor XIIIa (FXIIIa, the potentia
lly active a(2)-subunit of factor XIII), an enzyme that participates i
n blood coagulation by stabilizing the fibrin clot, is also active in
the nervous system where it may play a key role in the healing of inju
red tissue. We demonstrate that the plasma, macrophages and nerves of
fish contain a 55 kDa form of transglutaminase that cross-reacts immun
ologically with the a-subunit of FXIII in mammals (80 kDa). The fish e
nzyme in the plasma, unlike its mammalian counterpart, is active, poin
ting to a difference in control of the coagulation pathway in the two
species. Analysis of FXIIIa expression in mammalian neural tissues and
their response to injury revealed high levels of the enzyme in media
conditioned by peripheral nerves as compared with medium conditioned b
y nerves of the central nervous system. Furthermore, similarity was ob
served in the postinjury behavior of FXIIIa in regenerating nerve tiss
ues (peripheral nervous system of mammals and the central nervous syst
em of fish). We suggest that the postinjury level of factor XIIIa in t
he nervous system may be related to the tissue's regenerative capacity
, and that FXIIIa may therefore be a link underlying a possible associ
ation between the processes of blood coagulation and nerve healing.