I. Ferrer et al., MULTIPLE NEUROTROPHIC SIGNALS CONVERGE IN SURVIVING CA1 NEURONS OF THE GERBIL HIPPOCAMPUS FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA, Journal of comparative neurology, 394(4), 1998, pp. 416-430
Delayed cell death involving the CA1 area of the hippocampus was produ
ced following 5 minutes of transient forebrain ischemia in gerbils. Ce
ll death mainly affected CA1 pyramidal neurons, whereas parvalbumin-im
munoreactive (parv-ir) cells were spared. Synaptophysin immunoreactivi
ty was observed in the strata oriens and radiatum of CA1 for months, a
lthough immunoreactivity decreased in gerbils surviving 1 year post-is
chemia. Golgi studies disclosed a few pyramidal neurons with dendrites
, variably covered with dendritic spines, in the CA1 area of 1-year su
rviving gerbils. In the normal gerbil, the majority of CA1 neurons exp
ressed brain-derived neurotrophic factor (BDNF), tyrosine protein kina
se C (TrkC), fibroblast growth factor receptor 1 (Flg), transforming g
rowth factor-alpha (TGF-alpha), and epidermal growth factor-receptor (
EGF-R), but only a minority of cells were tyrosine protein kinase B (T
rkB)-immunoreactive. Marked reduction in the number of BDNF-, TrkC-, F
lg-, TGF-alpha-, and EGF-R-ir cells was observed in CA1 from 24 hours
to 1 year after ischemia. In contrast, TrkB-ir cells survived the isch
emic insult. Double-labeling immunohistochemistry disclosed that about
90% of surviving BDNF-ir and 85% of TrkB-ir neurons co-localized parv
albumin in the CA1 area. In control gerbils, only about 5% of BDNF-ir
cells in CA1 co-expressed TrkB. However, TrkB co-localized in about 95
% of surviving BDNF-ir neurons in CA1 in ischemic gerbils. In addition
, parvalbumin was co-expressed in about 90% of TrkC-, 95% Flg-, and 85
% EGF-R-ir surviving neurons in the stratum pyramidale of CA1. Finally
, basic fibroblast growth factor (bFGF) was expressed by reactive astr
ocytes from day 4 onwards. These data show that the subpopulation of T
rkB-/parv-ir neurons in CA1 survive the ischemic episode and that mult
iple neurotrophic signals converge in surviving neurons of the gerbil
hippocampus following transient forebrain ischemia. J. Comp. Neurol. 3
94:416-430, 1998. (C) 1998 Wiley-Liss, Inc.