11, 12 Given this, exogenous cells may well be a source of trophic support, promoting endogenous
repair such as neurogenesis, angiogenesis, and synaptogenesis.13 Mechanisms of action of stem cell therapy in CNS injury The neuroprotective effect of stem cells for the treatment of CNS injury has been shown in several preclinical studies. However, the exact mechanism remains controversial. Potential mechanisms currently under investigation include engraftment and transdifferentiation, modulation of the inflammatory milieu, Inhibitors,research,lifescience,medical and modulation of the systemic immunologic/inflammatory response. Lundberg et al14 administered human mesenchymal stem cells in the ipsilateral internal carotid artery of rats which had been Inhibitors,research,lifescience,medical subjected to experimental TBI. Intraarterial transplantion of mesenchymal stem cells resulted in CNS engraftment without thromboembolic ischemia. Kuh et al15 implanted human umbilical cord blood-derived progenitor cells (HUCBCs) into the injury site after spinal cord contusion in a rodent
model. The transplanted HUCBCs were differentiated into various neural cells, which were confirmed by double immunofluorescence staining of bromodeoxyuridine (BrdU) and glial Inhibitors,research,lifescience,medical fibrillary acidic protein (GFAP) and microtubule-associated protein-2 (MAP-2) staining. Locomotor testing showed functional improvement for all time points tested up to 8 weeks after spinal cord injury. BMS-345541 ic50 Salazar et al16 transplanted human Inhibitors,research,lifescience,medical neural stem cells into immunodeficient NOD-scid mice 30 days post spinal cord contusion
injury. The transplanted mice demonstrated significantly improved locomotor recovery compared with vehicle controls using open field locomotor testing and Cat Walk gait analysis. The transplanted neural stem cells exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Also, differentiated NSCs integrated with the host as was demonstrated by colocalization of human cytoplasm with discrete Inhibitors,research,lifescience,medical staining for the paranodal marker contactin-associated protein . Dramatic cerebral responses following TBI comprise inflammation, cell death, and modulation of trophic factor release. These cerebral modulations might be influenced by stem cells. Walker et al17 directly implanted MSCs into the brains of rats which had been subjected to TBI. Rolziracetam Brain supernatant analysis showed an increase in interleukin (IL)-6, which has both direct and indirect neurotrophic effects on neurons.18 Glazova et al19 implanted neuronal phenotype ES cells in mice after experimentally induced spinal cord injury. Transplantation of the ES cells activated both brainderived neurotrophic factor IL-6 signaling pathways in the host tissue, leading to activation of cAMP/PKA, phosporylation of cofilin and synapsin I, and promoting regenerative growth and neuronal survival.