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Evaluation of VDAC1 blockade effects at the damage length and functional recovery after spinal cord transection in rats

Grant number: 16/07687-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Vera Paschon
Grantee:Beatriz Cintra Morena
Home Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Spinal cord damage may develop from different insults as fights with weapons or knives, accidents and others, leading to a paraplegic or tetraplegic condition. After the first insult, besides many processes are activated to maintain the homeostasis, several processes may be harmful for the neuronal regeneration, such as glial scar formation, inflammation, and spread of cell death. In the case of a mechanical lesion, many cells are disrupted, releasing prejudicial particles such as calcium (Ca2+) in high concentration, glutamate, apoptosis products and damaged-associated molecular pattern (DAMP) that can worsen the progression of the injury. Interestingly, one of the first cell organelle affected is the mitochondria. VDAC1 is a mitochondrial transmembrane protein that regulates its morphology and structure, conducts ADP and modulates apoptosis and necrosis signals. VDAC1 has well-described roles in neurodegenerative diseases as Parkinson's and amyotrophic lateral sclerosis. Combining behavioral test and histochemistry experiments, the aim of this project is to elucidate the effects of VDAC1 blockade in locomotor function recovery and cell death spread after spinal cord injury. Wistar rats will be submitted to spinal cord transection and pharmacological treatment with 4,42-diisothiocyanatostilbene-2,22-disulfonic acid (DIDS), a VDAC1 blocker, directly in the lesion site. After 7 and 14 days, the motor and sensorial function recovery will be accessed by footprint analyzes, open field measures, BBB score, and neurologic evaluation. Moreover, we will analyze spinal cord after 1, 7 and 14 post-lesion employing molecular methods, as TUNEL assay and immunofluorescence. The techniques described above may contribute with future spinal cord therapies to restore locomotor function.