Effect of IGF-I gene therapy in the inflammatory response of microglia in a traumatic brain injury model

HERRERA, M.L.; FALOMIR LOCKHART, E.; MARCHESE, N.A.; DOLCETTI, F.; GARCÍA SEGURA, L.M.; HEREÑÚ, C.; BELLINI, M.J.

Buenos Aires

Congreso; 2ndFALAN Congress; 2016

Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN)

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. Neuroinflammation is well established as a key secondary injury mechanism after TBI, and contributes to the activation of glial cells. Such activation is mainly regulated by microglia and astroglia. Neurotrophic factors like insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in part by the regulation of gliosis. OBJECTIVE: In this study we assessed the efficacy of IGF-I gene therapy in reducing the inflammatory response of microglia after a stab wound injury. METHODS: Wistar male rats were divided into 3 experimental groups: G1: injected IP with RAd- IGF-1, G2: injected IP with Rad-GFP and G3: control with PBS, 14 days previous to stab wound injury in the cortex. One week after injury rats were sacrificed and gliosis was assessed by immunohistochemistry. The number of Iba I immunoreactive microglia were estimated in the cortex within a distance of 0- 1252,5um from the wound border, divided into five consecutives frames of 250,5x835,52um2. In addition, Iba I-positive cells were classified in two morphological phenotypes: reactive and nonreactive. RESULTS: The stab injury induced a significant increase in the density of total possitive cells respect to the contralateral hemisphere in G1 (p<0.05), G2 (p<0.05) and G3 (p<0.05), respectively. We observed a decrease in cellular density dependent on the distance from the wound edge (p<0.05), but there were no differences between groups (p>0.05). Regarding to Iba1 cells with non-reactive phenotype, there were an increase in the group treated with IGF-1, in the first two frames, respect to G2 (p<0.05). CONCLUSIONS: These findings suggest that IGF-I gene therapy may represent a new approach to reduce microglia inflammatory reaction in this model of TBI.