The severity of brain damage determines bone marrow stromal cell therapy efficacy in a traumatic brain injury model

BACKGROUND: Patients who survive traumatic brain injury (TBI) can undergo serious sensorial and motor function deficits. Once damage occurs, there is no effective treatment to bring patients to full recovery. Recent studies, however, show bone marrow stromal cells (BMSC) as a potential therapy for TBI. METHODS: This study was designed to determine whether the degree of neurologic deficits influences the efficacy of cell therapy using intracerebral transplantation of BMSC in an experimental model of chronically established TBI. Adult Wistar rats were subjected to weight-drop impact causing TBI. Two months later, the animals were classified according to levels of neurologic deficits. To achieve this, we used two different functional tests: the modified Neurologic Severity Score test and internal zone Permanence Time in Video-Tracking-Box analysis. Saline only or saline containing BMSC was injected into injured brain tissue of the animals that were classified having moderate or severe neurologic damage depending on the level of established functional deficits. All experimental groups were evaluated in the course of the following 2 months to study the efficacy of BMSC administration. The animals were then killed and their brains were studied. RESULTS: Our results showed that significant functional improvement was seen when BMSC was injected into animals with moderate brain damage, but no significant improvement was found in animals with severe functional deficits when compared with controls. CONCLUSION: These findings suggest that the severity of neurologic damage may determine the potential effect of cell therapy when applied to chronically established TBI. (J Trauma. 2012; 72: 1203-1212. Copyright (C) 2012 by Lippincott Williams & Wilkins)