The current work explores the therapeutic potential of experiential treatments for enhancing functional recovery and anatomical change after early brain damage. Normal rats and rats with perinatal cortical lesions (P2 or P7) were exposed to one of the following treatments: complex housing as juveniles, complex housing as adults, prenatal tactile stimulation, postnatal tactile stimulation, or postnatal handling (removal from the nest with no additional stimulaion). Behavior was assessed in adulthood the Morris water task and the Whishaw reaching task. There were sex differences in the details of the effect of experience on both behavioral recovery and brain morphology. For both sexes treatments initiated prior to or immediately after brain injury were most effective in improving functional outcome. This was correlated with changes in dendritic arborization and Acetylcholinesterase staining. The results suggest that behavioral treatments can be used to stimulate functional recovery after early brain injury. / v, [14], 208 leaves : ill. ; 28 cm.

A ballistic pendulum impulse generator was used to impact networks in primary culture growing on microelectrode arrays. This approach has the advantage of imparting pure tangential acceleration insults (50 to 300 g) with simultaneous morphological and electrophysiological multichannel monitoring for days before and after the impact. Action potential (AP) production, network activity patterns, and cell electrode coupling of individual units using AP waveshape templates were quantified. Network adhesion was maintained after tangential impacts up to 300g with minimal loss of pre-selected active units. Time lapse phase contrast microscopy revealed stable nuclei pre-impact, but post impact nuclear rotation in 95% of observations (n= 30). All recording experiments (n=31) showed a repeatable two-phase spike production response profile: recovery to near reference in 1-2 hrs, followed by a slow activity decay to a stable, level plateau approximately 30-40% below reference. Phase 1 consisted of a complex two-step recovery: rapid activity increase to an average 23.6% (range: 11-34%) below reference, forming a level plateau lasting from 5 to 20 min, followed by a climb to within 20% of reference where a second plateau was established for 1 to 2 hrs. Cross correlation profiles showed changes in firing hierarchy after impact, and in spontaneous network oscillatory activity. Native oscillations were found in the Delta band (2 to 3 Hz), and decreased by approximately 20% after impact. Under network disinhibition with bicuculline, oscillations were slower (0.8-1Hz) and decreased 40% after impact. These data link network performance deficits with microscopically observable subcellular changes.