PMID- 35693138 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2008-126X (Print) IS - 2228-7442 (Electronic) IS - 2008-126X (Linking) VI - 12 IP - 6 DP - 2021 Nov-Dec TI - Minocycline Enhance the Restorative Ability of Olfactory Ensheathing Cells by the Upregulation of BDNF and GDNF Expression After Spinal Cord Injury. PG - 777-788 LID - 10.32598/bcn.2021.1727.1 [doi] AB - INTRODUCTION: Spinal Cord Injury (SCI) is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss, and severe functional deficits. Neurotrophic factors are a potential treatment for reducing secondary damage, promoting axon growth; they are responsible for inducing myelination after injury. Olfactory Ensheathing Cells (OECs) and minocycline have promoted locomotor function after SCI. The present study investigated the neuroprotective effects of combined treatment with minocycline and OECs on spinal cord injury related to Brain-Derived Neurotrophic Factor (BDNF) and Glial Derived Neurotrophic Factor (GDNF) expressions after SCI. METHODS: Adult female rats were used to experimental SCI by weight compression method. Rats received an intraperitoneal minocycline injection (90 mg/kg) immediately after SCI and 24 h after injury. OECs were transplanted one week after the injury. The hindlimb function was assessed using Basso Beattie Bresnahan (BBB) locomotor rating scale and Electromyography (EMG). After 5 weeks, the spinal cord segment centered at the injury site was removed for histopathological analysis. Immunohistological and western blot assays were performed to observe the expression of NeuN, BDNF, GDNF, and Myelin Basic Protein (MBP). RESULTS: SCI induced the loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline+OECs increased the score of the BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results suggested that NeuN expression significantly increased in the minocycline+OECs group than other groups. Moreover, electromyography amplitude in treated rats was increased compared to the control group. BDNF, GDNF, and MBP expressions and the number of ventral motor neurons increased further by minocycline+OECs in SCI rats. CONCLUSION: The present study provides evidence that minocycline may facilitate recovery of locomotor function by OECs by increasing BDNF and GDNF expressions following SCI. HIGHLIGHTS: Combined treatment with Minocycline and OECs increased the locomotor function.The results showed that BDNF and GDNF expression increased by combined treatment with minocycline and OECs. PLAIN LANGUAGE SUMMARY: This study examined the effect of combined treatment with minocycline and olfactory ensheathing cell on the BDNF and GDNF expression after spinal cord injury model in rat. The results showed that injection of minocycline before transplantation of OECs enhances expression of neurotrophic factors that lead to an appropriate environment for transplanted OECs and increases neuronal survival that promotes tissue sparing and functional recovery. CI - Copyright(c) 2021 Iranian Neuroscience Society. FAU - Pourkhodadad, Soheila AU - Pourkhodadad S AUID- ORCID: 0000-0003-1550-0350 AD - Department of Animal Physiology, Faculty of Biology, Kharazmi University, Tehran, Iran. FAU - Oryan, Shahrbanoo AU - Oryan S AUID- ORCID: 0000-0001-5259-9156 AD - Department of Animal Physiology, Faculty of Biology, Kharazmi University, Tehran, Iran. FAU - Hadipour, Mohammad Mehdi AU - Hadipour MM AUID- ORCID: 0000-0001-7441-2292 AD - Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. FAU - Kaka, Gholamreza AU - Kaka G AUID- ORCID: 0000-0001-8599-6123 AD - Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. FAU - Sadraie, Seyed Homayoon AU - Sadraie SH AUID- ORCID: 0000-0001-6955-8035 AD - Department of Anatomy, School of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran. LA - eng PT - Journal Article DEP - 20211101 PL - Iran TA - Basic Clin Neurosci JT - Basic and clinical neuroscience JID - 101575211 PMC - PMC9168820 OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Electromyography OT - Glial derived neurotrophic factor OT - Minocycline OT - Myelin basic protein OT - Olfactory ensheathing cells OT - Spinal cord injury COIS- Conflict of interest The authors declared no conflict of interest. EDAT- 2022/06/14 06:00 MHDA- 2022/06/14 06:01 PMCR- 2021/11/01 CRDT- 2022/06/13 03:11 PHST- 2019/03/03 00:00 [received] PHST- 2020/04/10 00:00 [revised] PHST- 2020/04/27 00:00 [accepted] PHST- 2022/06/13 03:11 [entrez] PHST- 2022/06/14 06:00 [pubmed] PHST- 2022/06/14 06:01 [medline] PHST- 2021/11/01 00:00 [pmc-release] AID - bcn-12-777 [pii] AID - 10.32598/bcn.2021.1727.1 [doi] PST - ppublish SO - Basic Clin Neurosci. 2021 Nov-Dec;12(6):777-788. doi: 10.32598/bcn.2021.1727.1. Epub 2021 Nov 1.