<p>Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis</p>

Abstract

Purpose The present study was carried out to confirm the protective effect of extract of Ginkgo biloba (Ginaton) against ischemic neuronal damage post-treatment at 24 h after reperfusion in rats with middle cerebral artery occlusion (MCAO) and further reveal its possible mechanisms. Methods Adult male Sprague-Dawley rats were modeled by MCAO for 2 h. The rats were divided into three groups: sham, model, and Ginaton (50 mg/kg). All animals received treatment once a day for 14 days from 24 h after reperfusion. Modified neurological severity score test was performed in 1, 7 and 14 days after MCAO, and beam walking test was performed only 14 days after MCAO. Hematoxylin-eosin straining was implemented to measure infarct volume and immunohistochemical analysis was performed to calculate the number of neurons in ischemic cortex penumbra. Western blot was used to evaluate the expression of autophagy (Beclin1, LC3, AMPK, mTOR, ULK), mitochondrial dynamic protein (Parkin, DRP1, OPA1) and apoptosis (Bcl-2, Bax). Results Post-treatment with Ginaton for 14 days decreased neurological deficit score, promoted the recovery of motor function, and noticeably reduced infarct size. Besides, Ginaton also alleviated the loss of NeuN-positive cells in ischemic cortex penumbra. In ischemic cortex, Ginaton increased the expression of Beclin1 and LC3-Ⅱ, elevated the AMPK, mTOR and ULK1, and induced autophagy. Moreover, Ginaton treatment upregulated Parkin, DRP1, and OPA1, and elevated the ratio of Bcl-2/Bax in 14 days after MCAO reperfusion injury. Conclusion Ginaton exhibited obvious neuroprotective effects in MCAO rats with initial administered 24 h after MCAO. The mechanism of Ginaton included induction of autophagy via activation of the AMPK pathway, maintenance of mitochondrial homeostasis and inhibition of apoptosis.

Eriodictyol Attenuates MCAO-Induced Brain Injury and Neurological Deficits via Reversing the Autophagy Dysfunction

“…Ao et al reported that JLX001 could induce autophagy to alleviate cerebral ischemia injury by activating the AMPK-ULK1 signaling pathway (Ao et al, 2019 ). The neuroprotective mechanisms of Ginaton in ischemic brain injury mainly include activation of AMPK pathway induced autophagy, maintenance of mitochondrial homeostasis, and inhibition of apoptosis (Li et al, 2019 ). On the other hand, He et al ( 2019 ) found that Puerarin inhibited neuronal autophagy and plays a neuroprotective role in cerebral ischemia (Hongyun et al, 2017 ).…”

Anti-inflammatory effects of powdered product of Bu Yang Huan Wu decoction: Possible role in protecting against Transient Focal Cerebral Ischemia

“…While most studies including the present one examine the acute effects of BYHW on stroke, the effects of chronic treatment of BYHW are yet to be fully elucidated. Long-term effects of BYHW on suspected genes or target proteins related to inflammation and mitochondria homeostasis in ischemic stroke and peripheral artery diseases also warrant further research [9,26,27,28].…”

Progesterone Attenuates Stress-Induced NLRP3 Inflammasome Activation and Enhances Autophagy Following Ischemic Brain Injury

“…Wang et al [63] observed an increased LC3-II protein level after cardiac arrest; that peaked between 3 and 6 h and then gradually decreased by 24 h. Wei et al [34] confirmed an early increase in LC3-II at 6 and 12 h within the cortex from mice subjected to cardiac arrest. However, Wu et al [64] and Li et al [65] observed lower levels of autophagy markers in the ischemic cortex compared to non-ischemic controls at days 7 and 14 post-ischemia. This is consistent with our observations of reduced hippocampal levels of LC3-II, indicating that autophagy was impaired at later time points after global ischemia when microglial activation peaks.…”