Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain injury model via activation of PI3K/Akt signaling pathway.
OBJECTIVE
Neuronal autophagy and apoptosis play an irreplaceable role in brain injury pathogenesis and may represent a hopeful target for treatment. Previous studies have demonstrated that administration of quercetin-attenuated brain damage in a variety of brain injury models including traumatic brain injury (TBI). However, whether PI3K/Akt signaling pathway mediates the neuroprotection of quercetin following TBI is not well clarified. We sought to propose a hypothesis that quercetin could attenuate neuronal autophagy and apoptosis via enhancing PI3K/Akt signaling.


METHODS
All rats were randomly arranged into four groups as follows: sham group (n = 25), TBI group (n = 25), TBI + quercetin group (n = 25), TBI + quercetin + LY294002 group (n = 25). Quercetin (Sigma, USA, dissolved in 0.9% saline solution) was administered intraperitoneally at a dose of 50 mg/kg at 30 min, 12 h, and 24 h after TBI. The neurological impairment and spatial cognitive function was assessed by the neurologic severity score and Morris water maze, respectively. Immunohistochemistry staining and western blotting was used to evaluate the expression of LC3, p-Akt, caspase-3, Bcl-2, and Bax.


RESULTS
Quercetin treatment significantly attenuated TBI-induced neurological impairment (1-3 days, p < 0.05) and improved cognitive function (5-8 days, p < 0.05). Double immunolabeling demonstrated that quercetin significantly reduced the LC3-positive cells co-labeled with NeuN, whereas significantly enhanced p-Akt-positive cells co-labeled with NeuN. Furthermore, quercetin treatment reduced the expression of LC3、caspase-3 and Bax levels induced following TBI (p < 0.05), and increased the expression of p-Akt and Bcl-2 at 48 h (p < 0.05).


CONCLUSIONS
In conclusion, our observations indicate that post-injury treatment with quercetin could inhibit neuronal autophagy and apoptosis in the hippocampus in a rat model of TBI. The neuroprotective effects of quercetin may be related to modulation of PI3K/Akt signaling pathway.
a Department of Neurosurgery , Central Hospital of Cangzhou , Cangzhou , People's Republic of China.
Guoliang
G
Du
b Department of Neurosurgery , Second Hospital of Hebei Medical University , Shijiazhuang , People's Republic of China.
Zongmao
Z
Zhao
a Department of Neurosurgery , Central Hospital of Cangzhou , Cangzhou , People's Republic of China.
Yonghan
Y
Chen
a Department of Neurosurgery , Central Hospital of Cangzhou , Cangzhou , People's Republic of China.
Zonghao
Z
Li
a Department of Neurosurgery , Central Hospital of Cangzhou , Cangzhou , People's Republic of China.
Yaohui
Y
Tian
a Department of Neurosurgery , Central Hospital of Cangzhou , Cangzhou , People's Republic of China.
Zhifeng
Z
Liu
a Department of Neurosurgery , Central Hospital of Cangzhou , Cangzhou , People's Republic of China.
Bin
B
Liu
a Department of Neurosurgery , Central Hospital of Cangzhou , Cangzhou , People's Republic of China.
Jianqiang
J
Song
Apoptosis; Autophagy; PI3K/Akt; Quercetin; Traumatic brain injury