HO-1 inhibits Inflammatory Cytokines which favors BDNF Induced Neuroregeneration in Spinal Cord Injury of Dogs and improves Functional Recovery | [Abstract Book on International Conference on Life Sciences (ICLS-23) 11-12 May 22-23 • 2023]

Author(s):

1. Imdad Ullah Khan: Department of Veterinary surgery, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea; Faculty of Veterinary and Animal Sciences, Gomal University D I Khan

2. Yoon Yongseok: Department of Veterinary surgery, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.

3. Jo Kwang Rae: Department of Veterinary surgery, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.

4. Jung Taeseong: Department of Veterinary surgery, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.

5. Kim Wan Hee: Department of Veterinary surgery, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.

6. Kweon Oh-Kyeong: Department of Veterinary surgery, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea

Abstract:

The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation and apoptotic cell death. It also leads to the production of myelin inhibitory molecules which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During spinal cord injury, abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), matrix metalloproteinase, superoxide dismutase and myeloperoxidases which synergize neuronal apoptosis. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, an optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. It was aimed to selectively target inflammation and neuroregeneration at the injured area of spinal cord. Therefore the stem cells expressing HO-1 and BDNF genes were prepared through lenti virus gene transfection. In an experimental study on dogs, spinal cord injury was induced and were injected intraparenchymal with both HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) designated a combination group and were compared with dogs injected with HO-1 MSCs, BDNF MSCs, and GFP MSCs. It was found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed a reduced intraparenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Page(s): 38-38

DOI: DOI not available

Published: Journal: Abstract Book on International Conference on Life Sciences (ICLS-23) 11-12 May 22-23, Volume: 0, Issue: 0, Year: 2023

Keywords:

BDNF , Neuroregeneration , Spinal Cord Injury of Dogs

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