IGF-1 gene therapy reverses hippocampal alterations after spinal cord injury.

JURE, I; DE NICOLA, AF; FALOMIR LOCHHART; BELLINI MJ; DEL CORE J; LABOMBARDA, F

Simposio; 3er Simposio: Physiology and pathology of neuroglia, UNAM; 2020

UNAM

After spinal cord injury (SCI), patients exhibitcognitive deficits that could be related to hippocampal alterations. We havepreviously described hippocampal neuroinflammation, neurogenesis reduction andcognitive impairments in rats after chronic SCI. Since insulin-like growthfactor 1 (IGF-1) enhances neurogenesis and IGF1 gene therapy modifies the inflammatoryresponse and ameliorates cognitive impairments in other models, we decided toevaluate whether an adenoviral vector expressing IGF-1 could reversehippocampal alterations and cognitive deficits observed in rats after SCI.  Sixty days post-injury (dpi), rats wereinjected in the lateral ventricles with a recombinant adenoviral constructedharboring the cDNA of rat IGF-1 as a therapeutic virus 1 (RAd-IGF-1) or thecDNA of red fluorescent protein, as a control virus (RAd-DsRed) or salinesolution. Neurogenesis and cognitive hippocampal dependent-tasks were evaluated15dpi. As expected, the number of neuroblasts (doublecortin + cells) decreasedafter chronic SCI (p<0.01 SCI vs sham). After the treatment with RAd-IGF1,neurogenesis increased in lesioned rats (p<0.05 SCI+RAd-DsRed control vsSCI+Rad-IGF-1). Regarding cognitive performance, recognition and spatialworking memory were assayed 60dpi using the novel object recognition and Y-mazetest respectively. The discrimination index decreased 24 h after the familiarizationphase in the lesioned group (p<0.001 SCI vs Sham), while IGF-1 treatmentincreased the mentioned index in lesioned rats (p<0.05 SCI+RAd-DsRed vs SCI+RAd-IGF-1).The percentage of spontaneous alternations decreased in lesioned rats (p<0.01SCI vs Sham) while injured rats treated with the adenoviral IGF-1 injectionincreased the percentage of spontaneous alternation (p<0.05 SCI+RAd-DsRed vsSCI+RAd-IGF-1).  These results supportthat therapies which enhance endogenous IGF-1 expression might be a possible treatmentfor the encephalopathy developed by SCI.