Neuroprotective effects of neurotropin in a mouse model of hypoxic-ischemic brain injury

被引:11
作者
Hishiyama, Sohei [1 ]
Kotoda, Masakazu [1 ]
Ishiyama, Tadahiko [2 ]
Mitsui, Kazuha [2 ]
Matsukawa, Takashi [1 ]
机构
[1] Univ Yamanashi, Dept Anesthesiol, Fac Med, Chuo Ku, 1110 Shimokato, Yamanashi 4093898, Japan
[2] Univ Yamanashi, Univ Yamanashi Hosp, Surg Ctr, Chuo Ku, Yamanashi, Japan
关键词
Neurotropin; Hypoxic-ischemic brain injury; Inflammatory cytokine; INTERLEUKIN-6; STROKE; ACCUMULATION; EXPRESSION; RECEPTOR; ALPHA;
D O I
10.1007/s00540-019-02655-z
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
PurposeIschemic-hypoxic insult leads to detrimental effects on multiple organs. The brain is especially vulnerable, and it is hard to regenerate once damaged. Currently, therapeutic options are very limited. Previous studies have reported neuroprotective effects of neurotropin, a non-protein extract derived from the inflamed skin of rabbits inoculated with vaccinia virus, using a murine model of peripheral nerve injury and cultured cell lines. However, whether neurotropin might have protective effects against brain injuries remains unclear. We, therefore, investigated the neuroprotective effect of neurotropin and possible underlying mechanisms, using a mouse model of hypoxic-ischemic brain injury.MethodsHypoxic-ischemic brain injury was induced via a combination of the left common carotid artery occlusion and exposure to hypoxic environment (8% oxygen) in adult male C57BL/6 mice. Immediately following induction of hypoxia-ischemia, mice received either saline or 2.4 units of neurotropin. The survival rate, neurological function, infarct volume, and expression of inflammatory cytokines were evaluated.ResultsCompared to the control group, the neurotropin group exhibited a significantly higher survival rate (100% vs. 62.5%, p<0.05) and lower neurological deficit scores (1; 0-2 vs. 3; 0-5, median; range, p<0.05) after the hypoxic-ischemic insult. The administration of neurotropin also reduced infarct volume (18.35.1% vs. 38.3 +/- 7.2%, p<0.05) and mRNA expression of pro-inflammatory cytokines.Conclusions The post-treatment with neurotropin improved survival and neurological outcomes after hypoxic-ischemic insult. Our results indicate that neurotropin has neuroprotective effects against hypoxic-ischemic brain injury by suppressing pro-inflammatory cytokines.
引用
收藏
页码:495 / 500
页数:6
相关论文
共 29 条
[1]   Release of IL-6 After Stroke Contributes to Impaired Cerebral Autoregulation and Hippocampal Neuronal Necrosis Through NMDA Receptor Activation and Upregulation of ET-1 and JNK [J].
Armstead, William M. ;
Hekierski, Hugh ;
Pastor, Philip ;
Yarovoi, Serge ;
Higazi, Abd Al-Roof ;
Cines, Douglas B. .
TRANSLATIONAL STROKE RESEARCH, 2019, 10 (01) :104-111
[2]   A quantitative in situ hybridization and polymerase chain reaction study of microglial-macrophage expression of interleukin-1β mRNA following permanent middle cerebral artery occlusion in mice [J].
Clausen, BH ;
Lambertsen, KL ;
Meldgaard, M ;
Finsen, B .
NEUROSCIENCE, 2005, 132 (04) :879-892
[3]  
Cojocaru Inimioara Mihaela, 2009, Rom J Intern Med, V47, P393
[4]   Delayed administration of a potent cyclin dependent kinase and glycogen synthase kinase 3 β inhibitor produces long-term neuroprotection in a hypoxia-ischemia model of brain injury [J].
Cowper-Smith, C. D. ;
Anger, G. J. A. ;
Magal, E. ;
Norman, M. H. ;
Robertson, G. S. .
NEUROSCIENCE, 2008, 155 (03) :864-875
[5]   Pathobiology of ischaemic stroke: an integrated view [J].
Dirnagl, U ;
Iadecola, C ;
Moskowitz, MA .
TRENDS IN NEUROSCIENCES, 1999, 22 (09) :391-397
[6]   Rapid mitochondrial dysfunction mediates TNF-alpha-induced neurotoxicity [J].
Doll, Danielle N. ;
Rellick, Stephanie L. ;
Barr, Taura L. ;
Ren, Xuefang ;
Simpkins, James W. .
JOURNAL OF NEUROCHEMISTRY, 2015, 132 (04) :443-451
[7]   Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells [J].
Fukuda, Yu ;
Fukui, Takao ;
Hikichi, Chika ;
Ishikawa, Tomomasa ;
Murate, Kenichiro ;
Adachi, Takeshi ;
Imai, Hideki ;
Fukuhara, Koki ;
Ueda, Akihiro ;
Kaplan, Allen P. ;
Mutoh, Tatsuro .
BRAIN RESEARCH, 2015, 1596 :13-21
[8]   Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke [J].
Gelderblom, Mathias ;
Leypoldt, Frank ;
Steinbach, Karin ;
Behrens, Doerthe ;
Choe, Chi-Un ;
Siler, Dominic A. ;
Arumugam, Thiruma V. ;
Orthey, Ellen ;
Gerloff, Christian ;
Tolosa, Eva ;
Magnus, Tim .
STROKE, 2009, 40 (05) :1849-1857
[9]   Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke [J].
Gredal, Hanne ;
Thomsen, Barbara B. ;
Boza-Serrano, Antonio ;
Garosi, Laurent ;
Rusbridge, Clare ;
Anthony, Daniel ;
Moller, Arne ;
Finsen, Bente ;
Deierborg, Tomas ;
Lambertsen, Kate L. ;
Berendt, Mette .
NEUROREPORT, 2017, 28 (03) :134-140
[10]   The global and regional burden of stroke [J].
Hankey, Graeme J. .
LANCET GLOBAL HEALTH, 2013, 1 (05) :E239-E240