Systemic Administration of Allogeneic Cord Blood Mononuclear Cells in Adults with Severe Acute Contusion Spinal Cord Injury: Phase 1/2a Pilot Clinical Study-Safety and Primary Efficacy Evaluation.

OBJECTIVE: Phase 1 of the SUBSCI I/IIa (Systemic Umbilical Cord Blood Administration in Patients with Acute Severe Contusion Spinal Cord Injury) study focused on safety and primary efficacy of multiple systemic infusions of allogeneic unrelated human umbilical cord blood mononuclear cells in patients with severe acute spinal cord contusion having severe neurologic deficit. The primary end point was safety. The secondary end point was the restoration of motor and sensory function in lower limbs within a 1-year period. METHODS: Ten patients with acute contusion spinal cord injury (SCI) and American Spinal Injury Association (ASIA) level A/B deficit were enrolled into phase 1. Patients were treated with 4 infusions of group-matched and rhesus-matched cord blood samples after primary surgery within 3 days after SCI. All patients were followed up for 12 months after SCI. Safety was assessed using adverse events classification depending on severity and relation to cell therapy. Primary efficacy was assessed using dynamics of deficit (ASIA scale). RESULTS: The overall number of adverse events reached 419 in 10 patients. Only 2 were estimated as possibly related to cell therapy, and the remaining 417 were definitely unrelated. Both adverse events were mild and clinically insignificant. No signs of immunization were found in participants. Analysis of clinical outcomes also showed that cell therapy promotes significant functional restoration of motor function. CONCLUSIONS: The data obtained suggest that systemic administration of allogeneic, non-human leukocyte antigen-matched human umbilical cord blood is safe and shows primary efficacy in adults with severe acute contusion SCI and ASIA level A/B deficit.

A Translational Study on Acute Traumatic Brain Injury: High Incidence of Epileptiform Activity on Human and Rat Electrocorticograms and Histological Correlates in Rats.

BACKGROUND: In humans, early pathological activity on invasive electrocorticograms (ECoGs) and its putative association with pathomorphology in the early period of traumatic brain injury (TBI) remains obscure. METHODS: We assessed pathological activity on scalp electroencephalograms (EEGs) and ECoGs in patients with acute TBI, early electrophysiological changes after lateral fluid percussion brain injury (FPI), and electrophysiological correlates of hippocampal damage (microgliosis and neuronal loss), a week after TBI in rats. RESULTS: Epileptiform activity on ECoGs was evident in 86% of patients during the acute period of TBI, ECoGs being more sensitive to epileptiform and periodic discharges. A "brush-like" ECoG pattern superimposed over rhythmic delta activity and periodic discharge was described for the first time in acute TBI. In rats, FPI increased high-amplitude spike incidence in the neocortex and, most expressed, in the ipsilateral hippocampus, induced hippocampal microgliosis and neuronal loss, ipsilateral dentate gyrus being most vulnerable, a week after TBI. Epileptiform spike incidence correlated with microglial cell density and neuronal loss in the ipsilateral hippocampus. CONCLUSION: Epileptiform activity is frequent in the acute period of TBI period and is associated with distant hippocampal damage on a microscopic level. This damage is probably involved in late consequences of TBI. The FPI model is suitable for exploring pathogenetic mechanisms of post-traumatic disorders.