Neural grafts attenuate behavioral deficits produced by early radiation-induced hypoplasia of fascia dentata granule cells

Abstract

Localized X-irradiation of the mitotic cells in the neonatal rat hippocampus produces a discrete hypoplasia of the fascia dentata granule cell layer. This brain damage inhibits the acquisition of a passive avoidance task, and stimulates spontaneous perseverative turning (without reversals) in a plastic hemisphere apparatus. Here we report how transplantation of fetal brain tissue can attenuate these radiation-induced behavioral deficits. The partially shielded cerebral hemispheres of neonatal rats received fractionated exposures to 13 Gray (Gy) of X-rays during the first 16 days post partum. This procedure depleted 90% of the hippocampal granule cells while sparing other brain areas. Control animals were sham irradiated. Baseline behavioral tests were conducted when subjects reached an average age of 147 ± 4 days. We recorded behavioral parameters known to be sensitive to hippocampal damage: (1) passive avoidance performance, and (2) perseverative spontaneous turning without reversals. Irradiated subjects later (average age= 182 ± 4days) received intracerebral transplants of either fetal (E20–21) neurons/neuronal precursors from the fascia dentata or cerebral cortex (control grafts). Additional controls (both irradiated and sham-irradiated) experienced sham surgical procedures or received no surgical manipulation. Two post-surgical behavioral retests were accomplished when rats were 265 ± 5 and 351 ± 6 days old. Rats were then sacrificed and brains were treated histologically to assess radiation-induced brain damage, graft survivability and graft locus. Both hippocampaa and cerebral cortex grafts generally facilitated performance on the passive avoidance task. This effect was most prominent during the first post-surgical test. Hippocampal transplants (especially those found to reside in the damaged hippocampus) also significantly attenuated perseverative spontaneous rotation at the time of the final post-surgical test series. Cortex grafts found within the damaged hippocampus did not ameliorate perseverative movements, while cortex grafts located outside the hippocampus significantly reduced this behavioral deficiency. These data suggest that selected behavioral deficits may be attenuated by transplanting fetal neural tissue long after early radiation-induced brain damage. The success of these procedures depends on a number of factors including: (1) the behaviors chosen for analysis, (2) the time after transplantation that behavioral tests are conducted, and (3) the source and final location of the donor neural tissue.