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Rab7b Overexpression–Ameliorated Ischemic Brain Damage Following tMCAO Involves Suppression of TLR4 and NF-κB p65

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Abstract

Cerebral stroke is one of the leading causes of death and permanent disability worldwide. Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) p65 play a critical role in brain damage following ischemia-induced stroke. Rab7b, a lysosome-associated small Rab GTPase, has been implicated in TLR4 regulation; however, its role in cerebral stroke is poorly understood. In this study, by investigating a rat model with cerebral stroke, we found that Rab7b was upregulated in the rat brain following the transient middle cerebral artery occlusion (tMCAO). Functionally, overexpression of Rab7b in the brain by DNA transfection reduced cerebral infarction and improved neurological outcome following tMCAO, suggesting that Rab7b alleviates ischemic brain damage. Mechanistically, Rab7b overexpression suppressed the expression of TLR4 and NF-κB p65 and also inhibited the activation of NF-κB p65. Furthermore, Rab7b overexpression suppressed the production of proinflammatory mediators including TNF-α, IFN-γ, IL-1β, and IL-6 in the brain following tMCAO. In summary, these results suggest that Rab7b protects against ischemic brain damage following tMCAO and that this protection may relate to the suppressed inflammatory response mediated by TLR4 and NF-κB p65. Our study might offer Rab7b as a novel therapeutic target in the treatment of cerebral stroke.

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Authors and Affiliations

  1. Department of Neurology, Tianjin Baodi Hospital, No.8 of Guang Chuan Road, Baodi District, Tianjin, 301800, China

    Jinlong Qi, Yanhong Rong, Lu Wang, Junying Xu & Kun Zhao

Authors
  1. Jinlong Qi
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  2. Yanhong Rong
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  3. Lu Wang
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  4. Junying Xu
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  5. Kun Zhao
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Correspondence to Kun Zhao.

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All the animal experimental procedures were performed in accordance with the protocols approved by the Animal Care and Use Committee of Tianjin Baodi Hospital.

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The authors declare that they have no conflict of interest.

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Qi, J., Rong, Y., Wang, L. et al. Rab7b Overexpression–Ameliorated Ischemic Brain Damage Following tMCAO Involves Suppression of TLR4 and NF-κB p65. J Mol Neurosci 68, 163–170 (2019). https://doi.org/10.1007/s12031-019-01295-y

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  • DOI: https://doi.org/10.1007/s12031-019-01295-y

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