L. Feng, A. Sharma, F. Niu, H. Huang, J.V. Lafuenta, D.F. Muresanu, A. Ozkizilcik, Z.R. Tian, H.S. Sharma
Bethune International Peace Hospital,
Keywords: spinal cord injury, mesenchymal stem cells, cerebrolysin, nanowired delivery
Summary:Military personnel are often victims of spinal cord injury (SCI) for which there is no suitable treatment available. Thus, exploring new therapeutic avenues using select combination of novel neuroprotective agents is the need of the hour to improve the quality of life of SCI patients. Previous experiments from our laboratory show that a focal SCI inflicted in rat by making an incision of the right dorsal horn of the T10-11 segment resulted in pronounced functional disability on Tarlov Scale, inclined plane angle test and walking on a mesh grid in a progressive manner after 12 and 24 h trauma. This behavioral dysfunction correlated well with breakdown of the blood-spinal cord barrier (BSCB), edema formation and cell injuries seen in both the rostral and caudal segments after SCI in a progressive manner. Recording of spinal cord evoked potentials using epidural electrodes at rostral and caudal to lesion segments exhibited significant increase in latency and amplitude changes indicating loss of spinal cord conduction. Several lines of evidences suggest that intraspinal administration of mesenchymal stem cells (MSCs) improves functional outcome and enhance spinal cord conduction. However, MSCs induced restoration of BSCB and reduction in edema formation is not well known. In present investigation we examined the role of MSCs alone or in combination with cerebrolysin (CBL)- a multimodal drug on SCI induced restoration of cellular and behavioural functions in a rat model. SCI was inflicted in Equithesin anesthetized rats over the right dorsal horn of the T10-11 segments (2 mm deep and 4 mm long) and the animals were allowed to survive 12 or 24 h after trauma. In separate groups of SCI rats MSCs (106 cells) and CBL (50 µl) were administered into the rostral and caudal spinal cord around the lesion site after 3 h injury using a 100 µl Hamilton syringe connected to a constant infusion pump (10 µl/min). Since nanodelivery of MSCs or CBL has superior neuroprotective effects in CNS injury, we also examined TiO2 nanodelivery of MSCs and CBL in SCI. Our observations showed that co-administration of MSCs and CBL significantly reduced BSCB breakdown, edema formation and cell injuries at 12 h but not at 24 h after SCI. In this group significant improvement on behavioral function was seen after 12 h SCI. However, when TiO2-nanodelivery of MSCs and CBL was done in identical conditions, these treatment strategies significantly attenuated cord pathology and improved behavioral dysfunctions after 24 SCI. These observations are the first to show that intraspinal administration of nanowired MSCs and CBL have superior neuroprotective effects in SCI, not reported earlier.