title: The reciprocal interaction of sympathetic nervous system and cAMP-PKA-NF-kB pathway in immune suppression after experimental stroke.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.affiliation: Department of Neurology, The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, China. Electronic address: 1139598544@qq.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Geriatric Department, The First People's Hospital of Lianyungang, Lianyungang, China. Electronic address: shiluhangnanjing@163.com.
authors.forename: Luhang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Neurology, The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, China. Electronic address: yanfuling218@163.com.
authors.forename: Fuling
authors.initials: F
authors.lastname: Yan
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D020521:Stroke / Q000276:immunology* / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Immune depression; NF-kB; PKA; Stroke; Sympathetic nervous system; cAMP