The long-term fate of multiple intrahippocampal
allogeneic transplants of fetal basal
forebrain tissue was studied in neonatally
tolerised and immunised groups of rats with
lesions of the fimbria-fornix. Despite the good
survival of the allografts in all groups,
unexpected transplant-associated host hippo-campal
neuropathology was discovered 12
months after transplantation, which consisted of
(i) CA1 cell degeneration and (ii) abnormal
accumulations of phosphorylated neurofilaments
in neuronal perikarya and axonal swellings only
within the host hippocampal neuropil and not of
the transplanted tissue. This neurofilament
abnormality, identified by RT97 immunohistochemistry,
was significantly greater in the
transplanted rats compared to the non-grafted
lesion-only and sham-lesioned rats (p<0.01)
. The
same type of neurofilament abnormality was
again observed in a second, separate experiment
using unilateral and bilateral syngeneic and
allogeneic transplants. The neuropathology was
significantly (p<0.05)
greater in the transplanted
side of the unilateral transplanted rats
compared to the non-transplanted lesion-only
control side of the same animals, showing that
transplantation per se was a major factor
involved in the pathogenesis of this neuropathology,
irrespective of the type of transplant
(syngeneic or allogeneic). In addition, a small
degree of neurofilament abnormality was also
found within the transplants in the second
experiment, but not in the first. The results show
that, under certain conditions, specific local
neuropathological damage to the surrounding
host neural tissue can develop in long-surviving
allografted and syngrafted animals.