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The Effect of rhEPO on NTF Expression and Neuronal Apoptosis after Spinal Cord Injury

Author: ZhangZhenDong
Tutor: XuYouJia
School: Suzhou University
Course: Orthopedics
Keywords: Spinal cord injury Erythropoietin Apoptosis Caspase-3 Nerve growth factor Neurotrophin-3
CLC: R651.12
Type: Master's thesis
Year: 2007
Downloads: 183
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Abstract

Erythropoietin (EPO) is a molecular weight of about 34 kd, sialic acid-containing acid glycoprotein. EPO in the past has been considered only in the kidney secretion, is an effect on bone marrow cells, promote erythroid progenitor cell proliferation, differentiation, and ultimately mature endocrine hormones. Currently find, in addition to the kidneys, the liver, lung, spleen, placenta, reproductive organs and other tissues and organs of the EPO secretion, central nervous system (CNS) is also present EPO and EPO receptor (EpoR) gene is widely expressed; EPO in addition to outside of erythropoietin is essential, is a anti-inflammatory and immunomodulatory effects of the multi-nutritional factors and neuroprotective factor, development of the CNS and plays an important role in the regulation of CNS injury have good neuroprotective effect, so widely attention. This study intends to apply different time points after spinal cord injury erythropoietin intervention to explore their neuromotor functions and pathological changes secondary protective effect on neurotrophic factor expression and neuronal apoptosis, is divided into the following three parts: The first part of the spinal cord injury erythropoietin for NGF, NT-3 expression Objective: nerve growth factor (NGF) and neurotrophin -3 (NT-3) is a major neurotrophic factor family members are produced by the body can promote nerve cell survival, growth and differentiation factor for a class of peptides or proteins. It can prevent neuronal death after injury, promote neuronal repair, regulate synaptic plasticity and axonal regeneration neurotransmission and other nervous system function, is a reflection of the importance of spinal cord repair observed. In this study, spinal cord injury at different times after application of erythropoietin to explore their neuromotor functions and secondary pathological changes and the protective effect of nerve growth factor and neurotrophin-3 expression. Methods: Wistar rats were randomly divided into normal group, sham operation group, the control group, the experimental group. Allen hit by modified method in rats incomplete spinal cord injury model, the experimental group were 1 hour after spinal cord injury, 6 hours, 24 hours intraperitoneal injection of rhEPO, 5000ku/kg. Through animal neuromotor function score and histological staining nerve damage evaluation; using immunohistochemical staining of nerve growth factor and neurotrophin-3 expression levels. Results: In the 48 hours after spinal cord injury, rhEPO1 hours, 6 hours treatment group neuromotor functions and secondary pathological damage significantly improved swash plate angle experiment (43.5 ± 3.45; 42 ± 1.98) compared with the same period in the control group was significantly increased ( P lt; 0.05); Immunohistochemistry showed that spinal nerve growth factor and neurotrophin-3 expression was significantly increased, the difference was significant (P lt; 0.01); while 24 hours after the treatment group compared with the control group over the same period, the spinal cord nerve cell nerve growth factor and neurotrophin-3 expression were not statistically significant increase (P gt; 0.05). Conclusion: Early application of exogenous EPO on incomplete spinal cord injury caused by neuromotor dysfunction and secondary pathological changes has a protective effect, such a protective effect may be related to EPO can increase neurotrophin-3 and nerve growth factor expression, protect damaged neurons to promote spinal cord regeneration related. The second part of the spinal cord injury erythropoietin on the expression of Caspase-3 Objective: cysteine ??protease (Caspase) during apoptosis is considered the most important series of proteases, which Caspase-3 is the most important protease, is a common variety of apoptotic pathways downstream effects section. In this study, different times after spinal cord injury in rats by intraperitoneal injection of erythropoietin, explore their Caspase-3 expression. Methods: Wistar rats were randomly divided into normal group, sham operation group, the control group, rhEPO treatment group. Allen hit by modified method in rats incomplete spinal cord injury model, through animal neuromotor function score and histological staining nerve damage evaluation; using immunohistochemical staining nerve cells in the spinal cord of Caspase-3 expression levels. Results: Compared with the control group, spinal cord injury rhEPO1 hours, 6 hours and treated with neuromotor function significantly improved secondary pathological damage, spinal cord of Caspase-3 expression was significantly decreased (P lt; 0.01); while after 24 hours Compared with the control group, spinal cord neuronal apoptosis index and decreased expression of Caspase-3 was not statistically significant. Conclusion: Early application of exogenous EPO on incomplete spinal cord injury caused by neuromotor dysfunction and secondary pathological changes has a protective effect, such a protective effect may be related to EPO by reducing the expression of Caspase-3, thereby reducing secondary of neuronal apoptosis. The third part of the spinal cord injury erythropoietin on neuronal apoptosis Objective: neuronal apoptosis in spinal cord injury is an important pathological changes. In this study, different times after spinal cord injury in rats by intraperitoneal injection of erythropoietin to explore its effects on neuronal apoptosis. Methods: Wistar rats were randomly divided into normal group, sham operation group, the control group, the experimental group. Allen hit by modified method in rats incomplete spinal cord injury model, through animal neuromotor function score evaluation nerve damage; using the TUNEL assay spinal neuronal apoptosis index. Results: Compared with the control group, spinal cord injury erythropoietin 1 hour, 6 hours experimental group significantly improved neurological motor function, spinal cord nerve cell apoptosis index were significantly decreased (P lt; 0.01); while the group after 24 hours Compared with the control group, spinal cord neuronal apoptosis was no significant fall in the index Conclusion: Early application of exogenous EPO on incomplete spinal cord injury caused by neuromotor dysfunction has a protective effect, such a protective effect may be related to EPO reduce neuronal apoptosis.

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