BIONEURO – 62085/2008
       The effect of transplanting neural stem cells for the treatment of spinal cord injuries has been studied with great interest during the last two decades. Passing from studies on experimental rat models to clinical studies on humans have now begun in China and elsewhere and may soon begin in many Western European countries. Studies regarding transplants in spinal cord injuries have been done in the last years and are still in a research state. The primary olfactory system has a remarkable capacity of forming olfactory neurons continuously throughout the animal's life. The direct exposure of primary olfactory neurons to the external environment makes them more susceptible to chemical or traumatic injuries. Olfactory neurogenesis takes place in the basal cell layer of the olfactory epithelium, being enhanced after an injury to the primary olfactory system. New primary olfactory neurons grow axons to the olfactory bulb and establish novel functional connections. These axons grow along specialized glial cells, the OEG, which are found throughout the primary olfactory pathway from the lamina propria to the olfactory bulb. The mammalian primary olfactory system is the only neural tissue where axons are capable to grow directly into the central nervous system (CNS) throughout adulthood. In contrast to the vigorous neurogenesis and axonal growth that occurs following lesions of the mature primary olfactory system, injuries to the CNS and in particular, the spinal cord, results in permanent loss of neuronal connectivity. At the same time, recent studies on dogs have showed that the mucosa of the frontal sinus through its population of OEG and Schwann cells also has characteristics which can be valued through transplant in spinal cord injuries. The project aims to bring important data regarding the efficiency of the transplant of neural cells with regenerative potential (from the olfactory mucosa) and neural stem cells, in the functional recovery of patients with spinal cord injuries. To achieve this, studies will be made on experimental groups of dogs, which will be, in the first stage, assessed to establish a direct correlation between the degree of correspondence of clinical aspects and neurological imaging and electrophysiological exam, with the histological exam. At the same time, by identifying and stadializing the evolution of certain biomarkers of the neural inflammation in the cerebro-spinal fluid and assessing them from a quantitative/ qualitative point of view, it is aimed to establish an indirect protocol of lesion evaluation and determine the ideal moment for a viable transplant. Because the experimental models will be on groups of dogs, the data obtained can be applied in veterinary medicine and become the premises of experimental and clinical studies in human medicine. Using the advantages of sequential studies on the spinal cord pre- and post-transplant we will be able to offer consistent data regarding the rate of success of the transplants in direct correlation with the intimate modifications to the spinal cord tissue. The rate of success of the transplants will be appreciated in real time by correlating clinical data with neural imaging, testing the presence and evolution of the biomarkers of the process of rehabilitation of medullar architecture in the cerebro-spinal fluid, and the histological exam. This will identify and sequentialise the evolutive substrate of transplants in spinal cord injuries. The objectives of the project are: sequentialising of the pathological processes of the spinal cord induced by acute and chronical trauma as well as those degenerative and inflammatory; the study of neural stem cells and neural tissues with regenerative potential from the olfactory system and the frontal sinus mucosa; transplanting cells and neural tissues with stem potential in patients with spinal cord lesions; the clinical, electrophysiological and imagistic evaluation of the medullar transplant on experimental animal models and evaluating the possibility of transferring the results to human patients