Effect of IGF-1 gene therapy in the inflammatory response of microglia in a traumatic brain injury model

MACARENA LORENA HERRERA; EUGENIA FALOMIR LOCKHART; NATALIA MARCHESE; FRANCO DOLCETTI; LUIS MIGUEL GARCÍA SEGURA; CLAUDIA HEREÑÚ; MARÍA JOSÉ BELLINI

Buenos Aires

Congreso; Second FALAN Congress. XXXI Annual Congress of the Argentinean Society for Research in Neuroscience; 2016

FALAN | Federation of Latin American and Caribbean Neuroscience

BACKGROUND: 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 and the release of pro-inflammatory cytokines and chemokines. Such activation it is mainly regulated by microglia and astroglia. Neurotrophic factors like the insulin-like growth factor-I (IGF-I) exerts neuroprotective actions that are mediated at least in part by control of activation of glia. OBJECTIVE: In this study we have 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- HD-IGF-1, G2: injected IP with Rad-HD-GFP and G3: control with PBS, fourteen days previous to stab wound injury in the cortex. Two days 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 Iba1 immunoreactive cells respect to the contralateral hemisphere in G1 (t=2.588; p<0.05), G2 (t=4.756; p<0.05) and G3 (t=3.552; p<0.05), respectively. We observed in the 3 groups a decrease in cellular density as it moves away from the wound edge (F(4,48)=96,6; P<0.05), but there were no differences between the groups (F(8, 48)=0,3682; 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 (F(8, 12)=3,942; 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.