Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury

  • Authors:
    • Youquan Gu
    • Jun Chen
    • Tianhong Wang
    • Chaoning Zhou
    • Zhaodong Liu
    • Lanhua Ma
  • View Affiliations

  • Published online on: October 19, 2016     https://doi.org/10.3892/etm.2016.3821
  • Pages: 3767-3772
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Abstract

Traumatic brain injury (TBI) is the predominant cause of mortality in young adults and children living in China. TBI induces inflammatory responses; in addition, tumor necrosis factor‑α (TNF‑α), interleukin‑1β (IL‑1β), and IL‑6 are important pro‑inflammatory cytokines. Considering the observation that Hsp-70 overexpression can exert neuroprotection, identifying a drug that is able to induce the upregulation of Hsp70 has the potential to be a promising therapy for the treatment of neurological diseases. Thus, the present study assessed the clinical effectiveness of an anticancer drug and Hsp70 activator, 17‑allylamino-demethoxygeldanamycin (17‑AAG), to evaluate its potential as a treatment for patients with TBI. The aim of present study was to determine the neuroprotective effects of 17‑AAG following trauma and to investigate the underlying mechanisms of action. To establish rat models, rats were subjected to a controlled cortical impact injury and randomly divided into vehicle or 17‑AAG groups. In the 17‑AAG group, rats were administered with an intraperitoneal injection of 17‑AAG (80 mg/kg) immediately following the establishment of TBI. The motor function was measured using Neurologic Severity Score, and neuronal death was evaluated using immunofluorescence. The expression levels of GLT‑1, Bcl‑2 and Hsp‑70 were detected by western blot analysis and the expression levels of inflammatory cytokines were quantified using ELISA. The present study determined that 17‑AAG significantly reduced brain edema and motor neurological deficits (P<0.05), in addition to increasing neuronal survival. The aforementioned findings are associated with a downregulation of the expression levels of pro‑inflammatory cytokines TNF‑α, IL‑1β and IL‑6. Conversely, no significant changes of glutamate transporter‑1 expression were observed. The present results suggest that 17‑AAG treatment may provide a neuroprotective effect by reducing inflammation following TBI.
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December-2016
Volume 12 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Gu Y, Chen J, Wang T, Zhou C, Liu Z and Ma L: Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury. Exp Ther Med 12: 3767-3772, 2016.
APA
Gu, Y., Chen, J., Wang, T., Zhou, C., Liu, Z., & Ma, L. (2016). Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury. Experimental and Therapeutic Medicine, 12, 3767-3772. https://doi.org/10.3892/etm.2016.3821
MLA
Gu, Y., Chen, J., Wang, T., Zhou, C., Liu, Z., Ma, L."Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury". Experimental and Therapeutic Medicine 12.6 (2016): 3767-3772.
Chicago
Gu, Y., Chen, J., Wang, T., Zhou, C., Liu, Z., Ma, L."Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury". Experimental and Therapeutic Medicine 12, no. 6 (2016): 3767-3772. https://doi.org/10.3892/etm.2016.3821