Introduction: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. To date, there are no pharmacologic agents proven to improve outcomes from TBI because all the Phase I...

Exosomes play an important role in intercellular communication by delivering microribonucleic acids (miRNAs) to recipient cells. Previous studies have demonstrated that multi-potent mesenchymal stromal cell (MSC)-derived exosomes improve functional recovery after experimental traumatic brain injury (TBI). This study was performed to determine efficacy of miR-17-92 cluster-enriched exosomes (Exo-17-92) harvested from human bone marrow MSCs transfected with a miR-17-92 cluster plasmid in enhancing tissue and neurological recovery compared with exosomes derived from MSCs transfected with an empty plasmid vector (Exo-empty) for treatment of TBI. Adult male rats underwent a unilateral moderate cortical contusion. Animals received a single intravenous injection of miR-17-92 cluster-enriched exosomes (100 μg/rat, approximately 3.75x10 ¹¹ particles, Exo-17-92) or control exosomes (100 μg/rat, Exo-empty) or Vehicle (phosphate-buffered solution) one day after injury. A battery of neurological functional tests was performed weekly after TBI for five weeks. Spatial learning and memory were measured on days 31–35 after TBI using the Morris water maze test. All animals were sacrificed five weeks after injury. Their brains were processed for histopathological and immunohistochemical analyses of lesion volume, cell loss, angiogenesis, neurogenesis, and neuroinflammation. Compared with Vehicle, both Exo-17-92 and Exo-empty treatments significantly improved sensorimotor and cognitive function, reduced neuroinflammation and hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis without altering the lesion volume. Moreover, Exo-17-92 treatment exhibited a significantly more robust therapeutic effect on improvement in functional recovery by reducing neuroinflammation and cell loss, enhancing angiogenesis and neurogenesis than did Exo-empty treatment. Exosomes enriched with miR-17-92 cluster have a significantly better effect on improving functional recovery after TBI compared with Exo-empty, likely by reducing neuroinflammation and enhancing endogenous angiogenesis and neurogenesis. Engineering specific miRNA in exosomes may provide a novel therapeutic strategy for management of unilateral moderate cortical contusion TBI.

Object: Neurocan is a major form of growth-inhibitory molecule (growth-IM) that suppresses axonal regeneration after neural injury. Bone marrow stromal cells (MSCs) have been shown to inhibit neurocan expression in vitro and in animal models of cerebral ischemia. Therefore, the present study was designed to investigate the effects of treatment of MSCs impregnated with collagen scaffolds on neurocan expression after traumatic brain injury (TBI). Methods: Adult male Wistar rats were injured with controlled cortical impact and treated with saline, human MSCs (hMSCs) (3 × 10⁶) alone, or hMSCs (3 × 10⁶) impregnated into collagen scaffolds (scaffold + hMSCs) transplanted into the lesion cavity 7 days after TBI (20 rats per group). Rats were sacrificed 14 days after TBI, and brain tissues were harvested for immunohistochemical studies, Western blot analyses, laser capture microdissections, and quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to evaluate neurocan protein and gene expressions after various treatments. Results: Animals treated with scaffold + hMSCs after TBI showed increased axonal and synaptic densities compared with the other groups. Scaffold + hMSC treatment was associated with reduced TBI-induced neurocan protein expression and upregulated growth-associated protein 43 (GAP-43) and synaptophysin expression in the lesion boundary zone. In addition, animals in the scaffold + hMSC group had decreased neurocan transcription in reactive astrocytes after TBI. Reduction of neurocan expression was significantly greater in the scaffold + hMSC group than in the group treated with hMSCs alone. Conclusions: The results of this study show that transplanting hMSCs with scaffolds enhances the effect of hMSCs on axonal plasticity in TBI rats. This enhanced axonal plasticity may partially be attributed to the downregulation of neurocan expression by hMSC treatment after injury.

Spinal cord abscesses and spinal subdural empyemas are rare and difficult to treat. A 35-year-old male presented to an outside institution with 2 months of progressive low back pain, weakness, and bowel incontinence; he was diagnosed with an L4 epidural abscess that was poorly managed. When the patient presented to our institution, magnetic resonance imaging (MRI) revealed a well-organized chronic subdural abscess at the thoracolumbar junction. Following resection, his back pain resolved but he was left with a residual paraparesis. Subdural abscesses are rare and should be considered among the differential diagnoses for intraspinal mass lesions. Treatment should include prompt surgical exploration and decompression combined with appropriate prolonged antibiotic treatment.