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X-irradiation of the neonatal rat hippocampus produces a selective hypoplasia of fascia dentata granule cells, locomotor hyperactivity, perseverative movements and deficits in passive avoidance. We previously reported that transplantation of fetal hippocampal tissue into the adult (age = 182 +/- 4 days) brain produced a partial recovery of these behavioral deficits. Since graft/host interconnections are more prominent when transplants are conducted soon after radiation-induced hippocampal damage, in this study we transplanted hippocampal or cerebral cortex neurons when host rats were 33 +/- 5 days of age (i.e. only 16 days after radiogenic brain damage). Behavioral evaluations were conducted 80 and 182 days after transplantation or surgical control procedures. In the first test series only, selective components of locomotion (e.g. stereotypy and total distance traveled) and perseverative turning (e.g. mean bout length and turning speed topography) were normalized by the hippocampal grafts. Radiation-induced changes in passive avoidance were less prominent in these studies than in past experiments. Still, transplantation of hippocampal tissue improved performance on this learning task as well. Cerebral cortex grafts did not produce reliable improvements in most behavioral measures. These data suggest that hippocampal grafts placed soon after X-ray induced fascia dentata hypoplasia reduce a broad range of behavioral deficits. However, these benefits are transient and, for the most part, depend on the use of transplant tissues homologous with those damaged.

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 +/- 4 days) 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 hippocampal 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.

This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

Localized exposure of the neonatal rat brain to X-rays produces neuronal hypoplasia specific to the granule cell layer of the hippocampal dentate gyrus. This brain damage causes locomotor hyperactivity, slowed acquisition of passive avoidance tasks and long bouts of spontaneous turning (without reversals) in a bowl apparatus. Here we report how these behavioral deficits change as a function of subject aging and behavioral test replications. Portions of the neonatal rat cerebral hemispheres were X-irradiated in order to selectively damage the granule cells of the dentate gyrus. The brains of experimental animals received a fractionated dose of X rays (13 Gy total) over postnatal days 1 to 16 and control animals were sham-irradiated. Rats between the ages of 71-462 days were tested 3 separate times on each of the following 3 behavioral tests: 1) spontaneous locomotion, 2) passive avoidance acquisition, and 3) spontaneous circling in a large plastic hemisphere. Rats with radiation-induced damage to the fascia dentata exhibited long bouts of slow turns without reversals. Once they began, irradiated subjects perseverated in turning to an extent significantly greater than sham-irradiated control subjects. This irradiation effect was significant during all test series. Moreover, in time, spontaneous perseverative turning was significantly potentiated in rats with hippocampal damage but increased only slightly in controls. Early radiation exposure produced locomotor hyperactivity in young rats. While activity levels of controls remained fairly stable throughout the course of the experiment, the hyperactivity of the irradiated animals decreased significantly as they matured.(ABSTRACT TRUNCATED AT 250 WORDS)