Molecular approaches for spinal cord injury treatment

Injuries to the spinal cord result in permanent disabilities that limit daily life activities.The main reasons for these poor outcomes are the limited regenerative capacity of central neurons and the inhibitory milieu that is established upon traumatic injuries.Despite decades of research,there is still no efficient treatment for spinal cord injury.Many strategies are tested in preclinical studies that focus on ameliorating the functional outcomes after spinal cord injury.Among these,molecular compounds are currently being used for neurological recovery,with promising results.These molecules target the axon collapsed growth cone,the inhibitory microenvironment,the survival of neurons and glial cells,and the re-establishment of lost connections.In this review we focused on molecules that are being used,either in preclinical or clinical studies,to treat spinal cord injuries,such as drugs,growth and neurotrophic factors,enzymes,and purines.The mechanisms of action of these molecules are discussed,considering traumatic spinal cord injury in rodents and humans.

Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice

In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury （SCI） are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells （MSCs） in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T9 level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups： sham （anesthesia and laminectomy but without compression injury induction）, MSC i.p. （intraperitoneal injection of 8×10^5 MSCs in 500 μL of DMEM at 7 days after SCI）, MSC i.v. （intravenous injection of 8 × 10^5 MSCs in 500μL of DMEM at 7 days after SCI）, DMEM i.p. （intraperitoneal injection of 500μL of DMEM at 7 days after SCI）, DMEM i.v. （intravenous injection of 500 μL of DMEM at 7 days after SCI）. The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors （brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and neurotrophin-4） in the spinal cord and improved locomotor performance. Our results indicate that injection of MSCs by either intraperitoneal or intravenous routes results in beneficial outcomes and can be elected as a choice for SCI treatment.

Inosine: a novel treatment for sciatic nerve injury

Trauma to the peripheral nervous system often results in loss of motor and sensory functions of the affected area of the body,leading to a series of functional impairments(Allodi et al.,2012).Injuries to peripheral nerves initiate a series of complex events,known as Wallerian degeneration,which allows the injured axons to regenerate and reinnervate their targets(Allodi et al.,2012).Damage to a nerve induces multiple alterations,which include:axonal degeneration,breakdown of myelin sheath,Schwann cells(SC)proliferation and conversion to a repair phenotype which express cytokines and chemokines that allow the infiltration and activation of macrophages(Mietto et al.,2015;Jessen and Mirsky,2016).