Introduction: Nogo-A is one of the growth inhibitory molecules (growth-IMs) which inhibit axonal regeneration and neurite regrowth after neural injury. The present study was designed to investigate the suppressive effects of treatment with bone marrow stromal cells (MSCs) on the expression of Nogo-A, and induction of axonal regeneration after traumatic brain injury (TBI) in rats.
Methods: Adult male Wistar rats (n=32) were injured with controlled cortical impact and treated either with saline or MSCs (3x106) transplanted into the lesion cavity after impregnating them into collagen scaffolds 7 days after TBI (n=16/group). Rats were sacrificed 14 days after TBI and brain tissues were harvested for immunohistochemical studies, Western blot analysis, laser capture microdissections (LCM) and quantitative-reverse transcriptase-polymerase chain reaction (qRT-PCR) to evaluate axonal density and Nogo-A protein and gene expressions.
Results: Our data showed that treatment of TBI with MSCs significantly decreased TBI-induced Nogo-A protein expression and increased axonal density compared to saline treatment (p<0.05). In addition, MSC transplantation decreased Nogo-A transcription in oligodendrocytes after TBI (p<0.05).
Conclusions: Our results show that transplanting MSCs with scaffolds down-regulates Nogo-A transcription and protein expression which may partially contribute to the enhanced axonal regeneration seen after this treatment.
Patient Care: This study examines a new way of delivering treatment (suppression of Nogo-A via BMSs) in traumatic brain injury. The goal is to discover, verify then use these results to develop more effective treatments for patients suffering from traumatic brain injury.
Learning Objectives: By the conclusion of this session, participants should be able to: 1)describe Nogo-A and why it affects axonal regeneration and neurite regrowth after neural injury, 2) Be able to discuss how Nogo-A can be suppressed in TBI via treatment with bone marrow stromal cells, and 3) the effects of Nogo-A suppression in rats with TBI treated with bone marrow stromal cells.