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Planta Med 2019; 85(03): 231-238
DOI: 10.1055/a-0753-0400
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Icariin Improves Functional Behavior in a Mouse Model of Traumatic Brain Injury and Promotes Synaptic Plasticity Markers

Hyejin Joo
1   Department of Science in Korean medicine, Graduate School, Kyung Hee University, Seoul, Korea
2   Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
,
Jinhyun Bae
2   Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
,
Jun-Seon Lee
2   Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
,
Yumi Bang
2   Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
,
Beom-Joon Lee
3   Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Korea
,
Jae-Woo Park
3   Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Korea
,
Kyungjin Lee
2   Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
,
Jae-Heung Cho
4   Department of Korean Rehabilitation Medicine, Kyung Hee University, Seoul, Korea
,
Youngmin Bu
2   Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
› Author Affiliations
Further Information

Publication History

received 01 June 2018
revised 21 September 2018

accepted 26 September 2018

Publication Date:
09 October 2018 (online)

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Abstract

Epimedii Herba (EH) has been used in traditional Asian medicine to treat hemiplegia following stroke. Icariin, its major active component, is used as a quality-control marker and for its various pharmacological effects. We hypothesized that icariin would show protective effects following traumatic brain injury (TBI). The TBI mouse model was induced using a controlled cortical impact method. Body weight, brain damage, motor function, and cognitive function were evaluated. Synaptogenesis markers were analyzed to investigate potential mechanisms of action. The animals were divided into six groups: sham, control, minocycline-treated group, and icariin-treated (3, 10, and 30 mg/kg, p. o.) groups. The icariin 30 mg/kg-treated group regained body weight at 7 and 8 d post TBI. Icariin 30 mg/kg- and 10 mg/kg-treated groups showed enhanced sensory-motor function at 8 d post TBI in rotarod and balance beam tests. Icariin-treated groups showed increased recognition index in the novel object recognition test at all doses and increased spontaneous alternation in the Y-maze test at 30 mg/kg. Icariin upregulated brain-derived neurotrophic factor, synaptophysin and postsynaptic density protein 95 expressions. However, no protective effects against brain damage or neuronal death were observed. The current results provide a basis for using icariin following TBI and suggest that it could be a candidate for the development of therapeutic agents for functional recovery after TBI.

Key words

icariin - Epimedii Herba - traumatic brain injury - synaptic plasticity - functional recovery - Berberidaceae
 

  • References

  • 1 Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 2006; 21: 375-378
    CrossrefPubMedGoogle Scholar
  • 2 Xiong Y, Mahmood A, Chopp M. Animal models of traumatic brain injury. Nat Rev Neurosci 2013; 14: 128-142
    CrossrefPubMedGoogle Scholar
  • 3 Fozouni N, Chopp M, Nejad-Davarani SP, Zhang ZG, Lehman NL, Gu S, Ueno Y, Lu M, Ding G, Li L, Hu J, Bagher-Ebadian H, Hearshen D, Jiang Q. Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy. PLoS One 2013; 8: e76343
    CrossrefPubMedGoogle Scholar
  • 4 Rossini PM, Calautti C, Pauri F, Baron JC. Post-stroke plastic reorganisation in the adult brain. Lancet Neurol 2003; 2: 493-502
    CrossrefPubMedGoogle Scholar
  • 5 Ponsford J, Janzen S, McIntyre A, Bayley M, Velikonja D, Tate R, Panel IE. INCOG recommendations for management of cognition following traumatic brain injury, part I: posttraumatic amnesia/delirium. J Head Trauma Rehabil 2014; 29: 307-320
    CrossrefPubMedGoogle Scholar
  • 6 Kooda K, Aho J, Weber D, Brown A. 1149: The effect of antipsychotic use post-traumatic brain injury on duration of post-traumatic amnesia. Crit Care Med 2015; 43: 289
    PubMedGoogle Scholar
  • 7 Mysiw WJ, Bogner JA, Corrigan JD, Fugate LP, Clinchot DM, Kadyan V. The impact of acute care medications on rehabilitation outcome after traumatic brain injury. Brain Inj 2006; 20: 905-911
    CrossrefPubMedGoogle Scholar
  • 8 Hoffman AN, Cheng JP, Zafonte RD, Kline AE. Administration of haloperidol and risperidone after neurobehavioral testing hinders the recovery of traumatic brain injury-induced deficits. Life Sci 2008; 83: 602-607
    CrossrefPubMedGoogle Scholar
  • 9 Kwon D, Choi H, Lee J, Oh M, Bu Y. Bonchohak. Seoul: Younglim-sa; 2012
    Google Scholar
  • 10 Heo J. Japbyeongpyeon, Donguibogam. Seoul: Haeseongsa; 1610. (reprinted edition 1994).
    Google Scholar
  • 11 Ministry of Food and Drug Safety. The Korean Herbal Pharmacopoeia IV. Osong: Republic of Korea; 2017
    Google Scholar
  • 12 State Pharmacopoeia Committee. Pharmacopoeia of the Peopleʼs Republic of China. Beijing: China; 2015
    Google Scholar
  • 13 Indran IR, Liang RL, Min TE, Yong EL. Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health. Pharmacol Ther 2016; 162: 188-205
    CrossrefPubMedGoogle Scholar
  • 14 Ding J, Tang Y, Tang Z, Zu X, Qi L, Zhang X, Wang G. Icariin improves the sexual function of male mice through the PI3K/AKT/eNOS/NO signalling pathway. Andrologia 2018; 50: e12802
    CrossrefPubMedGoogle Scholar
  • 15 Cho JH, Jung JY, Lee BJ, Lee K, Park JW, Bu Y. Epimedii Herba: a promising herbal medicine for neuroplasticity. Phytother Res 2017; 31: 838-848
    CrossrefPubMedGoogle Scholar
  • 16 Zhang ZG, Wang X, Zai JH, Sun CH, Yan BC. Icariin improves cognitive impairment after traumatic brain injury by enhancing hippocampal acetylation. Chin J Integr Med 2018; 24: 366-371
    CrossrefPubMedGoogle Scholar
  • 17 Denes Z. The influence of severe malnutrition on rehabilitation in patients with severe head injury. Disabil Rehabil 2004; 26: 1163-1165
    CrossrefPubMedGoogle Scholar
  • 18 Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol 2015; 72: 355-362
    CrossrefPubMedGoogle Scholar
  • 19 Wu B, Chen Y, Huang J, Ning Y, Bian Q, Shan Y, Cai W, Zhang X, Shen Z. Icariin improves cognitive deficits and activates quiescent neural stem cells in aging rats. J Ethnopharmacol 2012; 142: 746-753
    CrossrefPubMedGoogle Scholar
  • 20 Dolenec P, Pilipovic K, Rajic J, Zupan G. Temporal pattern of neurodegeneration, programmed cell death, and neuroplastic responses in the thalamus after lateral fluid percussion brain injury in the rat. J Neuropathol Exp Neurol 2015; 74: 512-526
    CrossrefPubMedGoogle Scholar
  • 21 Tsenter J, Beni-Adani L, Assaf Y, Alexandrovich AG, Trembovler V, Shohami E. Dynamic changes in the recovery after traumatic brain injury in mice: effect of injury severity on T2-weighted MRI abnormalities, and motor and cognitive functions. J Neurotrauma 2008; 25: 324-333
    CrossrefPubMedGoogle Scholar
  • 22 Curzon P, Zhang M, Radek RJ, Fox GB. The behavioral Assessment of sensorimotor Processes in the Mouse: acoustic Startle, sensory Gating, locomotor Activity, Rotarod, and Beam Walking. In: Buccafusco JJ. ed. Methods of Behavior Analysis in Neuroscience. Boca Raton: CRC Press/Taylor & Francis; 2009: Chapter 8
    Google Scholar
  • 23 Baratz R, Tweedie D, Wang JY, Rubovitch V, Luo W, Hoffer BJ, Greig NH, Pick CG. Transiently lowering tumor necrosis factor-alpha synthesis ameliorates neuronal cell loss and cognitive impairments induced by minimal traumatic brain injury in mice. J Neuroinflammation 2015; 12: 45
    CrossrefPubMedGoogle Scholar
  • 24 Hammond RS, Tull LE, Stackman RW. On the delay-dependent involvement of the hippocampus in object recognition memory. Neurobiol Learn Mem 2004; 82: 26-34
    CrossrefPubMedGoogle Scholar
  • 25 Aggleton JP, Hunt PR, Rawlins JN. The effects of hippocampal lesions upon spatial and non-spatial tests of working memory. Behav Brain Res 1986; 19: 133-146
    CrossrefPubMedGoogle Scholar
  • 26 Sherman SM, Guillery RW. Exploring the Thalamus and its Role in cortical Function. 2nd ed.. London: The MIT Press; 2005
    Google Scholar
  • 27 Zhang ZG, Wang X, Zai JH, Sun CH, Yan BC. Icariin improves cognitive impairment after traumatic brain injury by enhancing hippocampal acetylation. Chin J Integr Med 2018; 24: 366-371
    CrossrefPubMedGoogle Scholar
  • 28 Lee BH, Kim YK. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investig 2010; 7: 231-235
    CrossrefPubMedGoogle Scholar
  • 29 Soler JE, Robison AJ, Nunez AA, Yan L. Light modulates hippocampal function and spatial learning in a diurnal rodent species: a study using male Nile grass rat (Arvicanthis niloticus). Hippocampus 2017; 28: 189-200
    PubMedGoogle Scholar
  • 30 Valtorta F, Pennuto M, Bonanomi D, Benfenati F. Synaptophysin: leading actor or walk-on role in synaptic vesicle exocytosis?. Bioessays 2004; 26: 445-453
    CrossrefPubMedGoogle Scholar
  • 31 Ansari MA, Roberts KN, Scheff SW. Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury. Free Radic Biol Med 2008; 45: 443-452
    CrossrefPubMedGoogle Scholar
  • 32 Rice RA, Spangenberg EE, Yamate-Morgan H, Lee RJ, Arora RP, Hernandez MX, Tenner AJ, West BL, Green KN. Elimination of microglia improves functional outcomes following extensive neuronal loss in the hippocampus. J Neurosci 2015; 35: 9977-9989
    CrossrefPubMedGoogle Scholar
  • 33 Tchantchou F, Tucker LB, Fu AH, Bluett RJ, McCabe JT, Patel S, Zhang Y. The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury. Neuropharmacology 2014; 85: 427-439
    CrossrefPubMedGoogle Scholar
  • 34 Rice RA, Pham J, Lee RJ, Najafi AR, West BL, Green KN. Microglial repopulation resolves inflammation and promotes brain recovery after injury. Glia 2017; 65: 931-944
    CrossrefPubMedGoogle Scholar
  • 35 Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008; 22: 659-661
    CrossrefPubMedGoogle Scholar
  • 36 Choi W, Lee K, Lee B, Park S, Park J, Ko C, Bu Y. The effects of chunghyul-dan, an agent of Korean medicine, on a mouse model of traumatic brain injury. Evid Based Integr Med 2017; 2017: 7326107
    PubMedGoogle Scholar
  • 37 Arvin KL, Han BH, Du Y, Lin SZ, Paul SM, Holtzman DM. Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. Ann Neurol 2002; 52: 54-61
    CrossrefPubMedGoogle Scholar
  • 38 Homsi S, Federico F, Croci N, Palmier B, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Minocycline effects on cerebral edema: relations with inflammatory and oxidative stress markers following traumatic brain injury in mice. Brain Res 2009; 1291: 122-132
    CrossrefPubMedGoogle Scholar
  • 39 George P, Keith BJ. The Mouse Brain in stereotaxic Coordinates. 2nd ed.. Cambridge: Academic Press; 2004
    Google Scholar
  • 40 Tucker LB, Fu AH, McCabe JT. Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research. J Neurotrauma 2016; 33: 880-894
    CrossrefPubMedGoogle Scholar
  • 41 Pandit V, Khan M, Zakaria ER, Largent-Milnes TM, Hamidi M, OʼKeeffe T, Vanderah TW, Joseph B. Continuous remote ischemic conditioning attenuates cognitive and motor deficits from moderate traumatic brain injury. J Trauma Acute Care Surg 2018; 85: 48-53
    CrossrefPubMedGoogle Scholar
  • 42 Aadal L, Mortensen J, Nielsen JF. Weight reduction after severe brain injury: a challenge during the rehabilitation course. J Neuroscience Nursing 2015; 47: 85-90
    PubMedGoogle Scholar