Intracranial bone marrow transplantation after traumatic brain injury improving functional outcome in adult rats

Abstract

Object. The authors tested the hypothesis that intracranial bone marrow (BM) transplantation after traumatic brain injury (TBI) in rats provides therapeutic benefit. Methods. Sixty-six adult Wistar rats, weighing 275 to 350 g each, were used for the experiment. Bone marrow prelabeled with bromodeoxyuridine (BrdU) was harvested from tibias and femurs of healthy adult rats. Other animals were subjected to controlled cortical impact, and BM was injected adjacent to the contusion 24 hours after the impact. The animals were killed at 4, 7, 14, or 28 days after transplantation. Motor function was evaluated both before and after the injury by using the rotarod test. After the animals had been killed, brain sections were examined using hemotoxylin and eosin and immunohistochemical staining methods. Histological examination revealed that, after transplantation, BM cells survived, proliferated, and migrated toward the injury site. Some of the BrdU-labeled BM cells were reactive, with astrocytic (glial fibrillary acid protein) and neuronal (NeuN and microtubule-associated protein) markers. Transplanted BM expressed proteins phenotypical of intrinsic brain cells, that is, neurons and astrocytes. A statistically significant improvement in motor function in rats that underwent BM transplantation, compared with control rats, was detected at 14 and 28 days posttransplantation. Conclusions. On the basis of their findings, the authors assert that BM transplantation improves neurological outcome and that BM cells survive and express nerve cell proteins after TBI.