The neuroprotective effect of a novel agent N2 on rat cerebral ischemia associated with the activation of PI3K/Akt signaling pathway
Authors: Nandani Darshika Kodithuwakku
Weirong Fang
Yi Zhou
Yunman Li
Wei He
Shaoxing Chu
Guangwei He
Qiang Wu
Jinru Huang
Wenxiang Fan
Journal: Neuropharmacology (2015)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Cerebral ischemia; N2; Neuron apoptosis.
Affiliations: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China., State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: ., Hefei Yigong Medicine Co., Ltd., Hefei, Jiangsu, PR China.

Abstract:  Ischemic stroke is the third leading cause of death and the main reason for severe disabilities in the world today. N2, 4 - (2 - (1H - imidazol - 1 - yl) ethoxy) - 3 - methoxybenzoic acid is considered as a novel potent agent for cerebral ischemia due to its effect in preventing neuronal cell death after ischemic stroke. In the present study, we investigated the post-ischemic neuroprotective effect of N2 and its underlying mechanisms. Using a MCAO rat model, we found that N2 reversed brain infarct size, reduced cerebral edema and decreased the neurological deﬁcit score significantly. Moreover, N2 diminished TUNEL positive cells, down-regulated bax expression and up-regulated bcl-2 expression notably. In addition, we evaluated the oxygen glucose deprivation/reoxygenation (OGD/R) injury induced neuron cell death in rat primary cortical neuron and assessed the neuroprotective effect of our drug. N2 increased cell viability, ameliorated neuron cell injury by decreasing LDH activity, and inhibited cell apoptotic rate while suppressed apoptotic signaling via inhibiting the bax expression, and elevating the bcl-2 expression. Furthermore, the neuroprotective effect of N2 was associated with the PI3K/Akt pathway which was proved by the use of PI3K inhibitor LY294002. The combination of our findings disclosed that N2 can be used as an effective neuroprotective agent for ischemic stroke due to its significant effect on preventing neuronal cell death after cerebral ischemia both in vivo and in vitro and the effectiveness was dose dependent. 

Retracted: No

PubPeer comments:
 This publications contains figure items that were also published in: https: doi.org 10.3389 fncel.2015.00517 ![file] ![file] ![file] , 
 RETRACTION: Front. Cell. Neurosci., 12 January 2016 | https: doi.org 10.3389 fncel.2015.00517 The journal retracts the 12 January 2016 article cited above. Following publication, it has been brought to our attention that several figures included in the article above appear identical to figures published by the authors in a separate article, u201cThe neuroprotective effect of a novel agent N2 on rat cerebral ischemia associated with the activation of PI3K Akt signaling pathwayu201d (doi: 10.1016 j.neuropharm.2015.02.022.), published in Neuropharmacology, February 2015. Specifically, the Bax-sham and Bax-AR(32mg kg) panels in Figure 2A of the Frontiers in Cellular Neuroscience publication appear identical to the D and F panels in Figure 5C of the Neuropharmacology publication, respectively. The TUNEL-AR(16mg kg) panel in Figure 2A of the Frontiers in Cellular Neuroscience publication also appears identical to panel C in Figure 4A of the Neuropharmacology publication. The authors concur with the retraction and sincerely regret any inconvenience this may have caused to the reviewers, editors and readers of Frontiers in Cellular Neuroscience. ,