Prolonged neurological dysfunction that results from an insult to the brain is often attributed to irreversible structural damage such as loss of neurons or axonal degeneration. For example, following cerebral ischemia even partial hippocampal CA1 neuronal loss has been proposed to be sufficient to result in deficits in hippocampal dependent spatial memory. This study examined if hippocampal CA1 neuronal loss and/or axonal injury was necessary to produce prolonged spatial memory deficits resulting from traumatic brain injury (TBI). Prior to TBI Sprague-Dawley rats were trained on an 8-arm radial maze, a task sensitive to detecting specific lesions of the hippocampus or its extrinsic connections. Following a mild, moderate, or sham injury, rats were tested for working and reference memory for 25 days. After 25 days of maze testing, histological cell counts were made from consistent coronal sections of the mid-dorsal hippocampus. Rats subjected to mild or moderate TBI manifested working memory deficits for 5 and 15 days, respectively, after injury in the absence of overt (all brain regions) or quantitative (CA1 only) evidence of neuronal death. The number of CA1 pyramidal neurons of representative sections of the mid-dorsal hippocampi for injured maze-deficit rats and sham control rats were: 1626 (S.E.M. = +/- 66) and 1693 (S.E.M. = +/- 69) per 10(6) micron2, respectively. Additionally, no overt evidence of axonal injury was observed in any forebrain structure including major intrinsic or extrinsic connecting hippocampal pathways. These data strongly suggest that mild to moderate TBI is capable of producing prolonged spatial memory deficits in the rat without evidence of either neuronal cell death in the intrinsic hippocampus or overt axonal injury in hippocampal pathways.