AAV6 mediated Gsx1 expression in neural stem progenitor cells promotes neurogenesis and restores locomotor function after contusion spinal cord injury.

Genomic screened homeobox 1 (Gsx1 or Gsh1) is a neurogenic transcription factor required for the generation of excitatory and inhibitory interneurons during spinal cord development. In the adult, lentivirus (LV) mediated Gsx1 expression promotes neural regeneration and functional locomotor recovery in a mouse model of lateral hemisection spinal cord injury (SCI). The LV delivery method is clinically unsafe due to insertional mutations to the host DNA. In addition, the most common clinical case of SCI is contusion/compression. In this study, we identify that adeno-associated virus serotype 6 (AAV6) preferentially infects neural stem/progenitor cells (NSPCs) in the injured spinal cord. Using a rat model of contusion SCI, we demonstrate that AAV6 mediated Gsx1 expression promotes neurogenesis, increases the number of neuroblasts/immature neurons, restores excitatory/inhibitory neuron balance and serotonergic neuronal activity through the lesion core, and promotes locomotor functional recovery. Our findings support that AAV6 preferentially targets NSPCs for gene delivery and confirmed Gsx1 efficacy in clinically relevant rat model of contusion SCI.

Biomarkers from Secondary Complications in Spinal Cord Injury.

Purpose of Review: In the USA, spinal cord injury (SCI) occurs in 40 people per million every year due to events such as car accidents, falls, violence, or sports injury. Secondary complications that arise from SCI are life-threatening and should be treated as early as possible. In some cases, it is not completely obvious what complication a patient may have until it is too late. Therefore, biomarkers are required to assess the levels of secondary complications after SCI. As there are several complications that pose different warning signs, different biomarkers may be beneficial in early detection, maintenance, and long-term care for patients with SCI. Recent Findings: Numerous studies have been conducted on biomarkers in various SCI and its related complications, such as neuropathic pain and deep vein thrombosis. In recent years, research has expanded with biomarkers discovered by cellular and molecular, genome-wide transcriptomic analysis, bioinformatics, and clinical studies. Biomarkers have allowed early prediction of the severity of secondary complications due to SCI. Summary: In this review, we summarize recent studies on the common biomarkers for the secondary complications related to SCI. We highlight the reliable biomarkers that have been tested, e.g., sclerostin, NGF, D-dimer, oncostatin M (OSM), microbiota, and C-reactive protein, which are valuable and with clinical importance. This review also emphasizes continuing research in biomarkers as they can provide valuable cellular and molecular insight into secondary complications after SCI.