Lei Zuo1, Luhang Shi2, Fuling Yan3. 1. Department of Neurology, The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, China. Electronic address: 1139598544@qq.com. 2. Geriatric Department, The First People's Hospital of Lianyungang, Lianyungang, China. Electronic address: shiluhangnanjing@163.com. 3. Department of Neurology, The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, China. Electronic address: yanfuling218@163.com.
Abstract
BACKGROUND: Sympathetic nervous system(SNS) is involved in the mechanism of immune suppression after stroke. Furthermore, as the pro-inflammatory effect of nuclear factor kappa B(NF-kB) is inhibited after stroke, which is regulated by cyclic adenosine monophosphate(cAMP) and proteinkinase A(PKA). The cAMP-PKA-NF-kB pathway might play an important role in noradrenergic-mediated immune dysfunction. AIM: The purpose of our research is to analyze how SNS interfere with the immune system after acute stroke and the underlying mechanism of cAMP-PKA-NF-kB pathway in regulating the inflammation. METHODS: 32 healthy male Sprague-Dawley rats were divided into 4 groups equally and randomly (1) Sham operation group; (2) middle cerebral artery occlusion; (MCAO) control group; (3) propranolol MCAO group; (4) isopropylarterenol sham group. 72h later after MCAO or sham operation, tumor necrosis factor-α(TNF-α)and interleukine-10(IL-10) in serum as well as cAMP, PKA and NF-kB in spleen cells were tested. RESULTS: TNF-α decreased while IL-10 increased in serum after acute ischemia stroke (p<0.05). Meanwhile, the levels of cAMP and PKA in spleen both increased in MCAO model while the expression of NF-kB was inhibited (p<0.05). When propranolol was used to inhibit SNS, all of the results reversed (p<0.05). But the reversed results were still significantly different from the sham operation group (p<0.05). Isopropylarterenol administrated rats appeared the same trend as MCAO group when compared to the sham operation group (p<0.05). However, the differences still existed (p<0.05). CONCLUSION: On account of the SNS activation after stroke, epinephrine activates the expression of cAMP, which further increases the level of PKA. Therefore, the level of nuclear factor NF-kB is down-regulated. Since the pro-inflammatory effect of NF-kB slacked, the immune system may be inhibited after stroke.
BACKGROUND: Sympathetic nervous system(SNS) is involved in the mechanism of immune suppression after stroke. Furthermore, as the pro-inflammatory effect of nuclear factor kappa B(NF-kB) is inhibited after stroke, which is regulated by cyclic adenosine monophosphate(cAMP) and proteinkinase A(PKA). The cAMP-PKA-NF-kB pathway might play an important role in noradrenergic-mediated immune dysfunction. AIM: The purpose of our research is to analyze how SNS interfere with the immune system after acute stroke and the underlying mechanism of cAMP-PKA-NF-kB pathway in regulating the inflammation. METHODS: 32 healthy male Sprague-Dawley rats were divided into 4 groups equally and randomly (1) Sham operation group; (2) middle cerebral artery occlusion; (MCAO) control group; (3) propranololMCAO group; (4) isopropylarterenol sham group. 72h later after MCAO or sham operation, tumor necrosis factor-α(TNF-α)and interleukine-10(IL-10) in serum as well as cAMP, PKA and NF-kB in spleen cells were tested. RESULTS: TNF-α decreased while IL-10 increased in serum after acute ischemia stroke (p<0.05). Meanwhile, the levels of cAMP and PKA in spleen both increased in MCAO model while the expression of NF-kB was inhibited (p<0.05). When propranolol was used to inhibit SNS, all of the results reversed (p<0.05). But the reversed results were still significantly different from the sham operation group (p<0.05). Isopropylarterenol administrated rats appeared the same trend as MCAO group when compared to the sham operation group (p<0.05). However, the differences still existed (p<0.05). CONCLUSION: On account of the SNS activation after stroke, epinephrine activates the expression of cAMP, which further increases the level of PKA. Therefore, the level of nuclear factor NF-kB is down-regulated. Since the pro-inflammatory effect of NF-kB slacked, the immune system may be inhibited after stroke.
Authors: Jalila Chagraoui; Bernhard Lehnertz; Simon Girard; Jean Francois Spinella; Iman Fares; Elisa Tomellini; Nadine Mayotte; Sophie Corneau; Tara MacRae; Laura Simon; Guy Sauvageau Journal: PLoS One Date: 2019-11-08 Impact factor: 3.240
Authors: Thomas Schmoch; Florian Uhle; Benedikt H Siegler; Thomas Fleming; Jakob Morgenstern; Peter P Nawroth; Markus A Weigand; Thorsten Brenner Journal: Int J Mol Sci Date: 2017-03-17 Impact factor: 5.923