Intracisternal IGF‐1 gene therapy abrogates kainic acid‐induced excitotoxic damage of the rat spinal cord

• Published in: The European journal of neuroscience Vol. 52; no. 5; pp. 3339 - 3352
• Main Authors: Nishida, Fabián, Zanuzzi, Carolina N., Sisti, María S., Falomir Lockhart, Eugenia, Camiña, Agustina E., Hereñú, Claudia B., Bellini, María J., Portiansky, Enrique L.
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.09.2020
• Subjects: adenoviral gene therapy; Animal models; Brain injury; Central nervous system; Excitotoxicity; Gene therapy; Injection; Insulin; Insulin-like growth factors; intracisternal route; Kainic acid; Nervous system; Neurological diseases; Neuronal-glial interactions; Neuroprotection; neurotoxicity; neurotrophic factor; Neurotrophic factors; Spinal cord; Spinal cord injuries; adenoviral gene therapy; neurotoxicity; neurotrophic factor; intracisternal route
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.14876

Development of alternative therapies for treating functional deficits after different neurological damages is a challenge in neuroscience. Insulin‐like growth factor‐1 (IGF‐1) is a potent neurotrophic factor exerting neuroprotective actions in brain and spinal cord. It is used to prevent or treat injuries of the central nervous system using different administration routes in different animal models. In this study, we evaluated whether intracisternal (IC) route for IGF‐1 gene therapy may abrogate or at least reduce the structural and behavioral damages induced by the intraparenchymal injection of kainic acid (KA) into the rat spinal cord. Experimental (Rad‐IGF‐1) and control (Rad‐DsRed‐KA) rats were evaluated using a battery of motor and sensory tests before the injection of the recombinant adenovector (day −3), before KA injection (day 0) and at every post‐injection (pi) time point (days 1, 2, 3 and 7 pi). Histopathological changes and neuronal and glial counting were assessed. Pretreatment using IC delivery of RAd‐IGF‐1 improved animal's general condition and motor and sensory functions as compared to Rad‐DsRed‐KA‐injected rats. Besides, IC Rad‐IGF‐1 therapy abrogated later spinal cord damage and reduced the glial response induced by KA as observed in Rad‐DsRed‐KA rats. We conclude that the IC route for delivering RAd‐IGF‐1 prevents KA‐induced excitotoxicity in the spinal cord. Intracisternal pretreatment with RAd‐IGF‐1 gene therapy abrogated the damage induced by the intraparenchymal injection of kainic acid (KA) in the rat spinal cord. As compared to Rad‐DsRed‐KA control group, the use of RAd‐IGF‐1 gene therapy improved animal's general condition, motor and sensory functions and reduced the structural spinal cord damage and glial response induced by KA.