Acidic preconditioning protects against ischemia-induced brain injury

Zhang, Chen-Hui; Fan, Yanying; Wang, Xiaofen; Xiong, Jie; Tang, Yingying; Gao, Jieqiong; Shen, Zhe; Song, Xiaohui; Zhang, Jingying; Shen, Yao; Li, Qing; Zhang, Xiangnan; Chen, Zhong

doi:10.1016/j.neulet.2012.05.015

Cited by 19 publications

(18 citation statements)

References 27 publications

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“…48 Briefly, the dissected cortex from E17 fetal mice was treated with 0.125% trypsin in Hank's buffer (in mmol/L: 137 NaCl, 5.4 KCl, 0.4 KH 2 PO 4 , 0.34 Na 2 PO 4 ·7H 2 O, 10 glucose and 10 HEPES) for 12 min at 37 °C and dissociated by repeated passage through a series of fire-polished Pasteur pipettes. Approximate 2 × 10 5 cells/cm 2 were seeded onto poly-l-lysine (10 µg/ml)-coated plates and dishes.…”

Section: Transient Mcao Mouse Model and Drugs Administrationmentioning

confidence: 99%

Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury

Zhang¹,

et al. 2014

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Transient cerebral ischemia leads to endoplasmic reticulum (ER) stress. However, the contributions of ER stress to cerebral ischemia are not clear. To address this issue, the ER stress activators tunicamycin (TM) and thapsigargin (TG) were administered to transient middle cerebral artery occluded (tMCAO) mice and oxygen-glucose deprivation-reperfusion (OGD-Rep.)-treated neurons. Both TM and TG showed significant protection against ischemia-induced brain injury, as revealed by reduced brain infarct volume and increased glucose uptake rate in ischemic tissue. In OGD-Rep.-treated neurons, 4-PBA, the ER stress releasing mechanism, counteracted the neuronal protection of TM and TG, which also supports a protective role of ER stress in transient brain ischemia. Knocking down the ER stress sensor Eif2s1, which is further activated by TM and TG, reduced the OGD-Rep.-induced neuronal cell death. In addition, both TM and TG prevented PARK2 loss, promoted its recruitment to mitochondria, and activated mitophagy during reperfusion after ischemia. The neuroprotection of TM and TG was reversed by autophagy inhibition (3-methyladenine and Atg7 knockdown) as well as Park2 silencing. The neuroprotection was also diminished in Park2(+/-) mice. Moreover, Eif2s1 and downstream Atf4 silencing reduced PARK2 expression, impaired mitophagy induction, and counteracted the neuroprotection. Taken together, the present investigation demonstrates that the ER stress induced by TM and TG protects against the transient ischemic brain injury. The PARK2-mediated mitophagy may be underlying the protection of ER stress. These findings may provide a new strategy to rescue ischemic brains by inducing mitophagy through ER stress activation.

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Section: Transient Mcao Mouse Model and Drugs Administrationmentioning

confidence: 99%

Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury

Zhang¹,

et al. 2014

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“…Induced simply by inhaling 20% CO 2 , APC significantly reduces focal cerebral ischemia and allows a wider time window for reperfusion than ischemic postconditioning (IPC) 8 . APC can preserve mitochondrial membrane potential, and, similarly, acidic pre-conditioning, where CO 2 is inhaled before ischemia, also alleviates mitochondrial dysfunction 9 . ASIC1/ASIC1α (acid-sensing [proton-gated] ion channel 1), the primary proton sensor in the nervous system, is localized in mitochondria and decreases mitochondrial membrane potential upon oxidative stress 10 .…”

Section: Introductionmentioning

confidence: 99%

PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window

Shen

Zheng

et al. 2017

Autophagy

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Prompt reperfusion after cerebral ischemia is critical for neuronal survival. Any strategies that extend the limited reperfusion window will be of great importance. Acidic postconditioning (APC) is a mild acidosis treatment that involves inhaling CO2 during reperfusion following ischemia. APC attenuates ischemic brain injury although the underlying mechanisms have not been elucidated. Here we report that APC reinforces ischemia-reperfusion-induced mitophagy in middle cortical artery occlusion (MCAO)-treated mice, and in oxygen-glucose deprivation (OGD)-treated brain slices and neurons. Inhibition of mitophagy compromises neuroprotection conferred by APC. Furthermore, mitophagy and neuroprotection are abolished in Park2 knockout mice, indicating that APC-induced mitophagy is facilitated by the recruitment of PARK2 to mitochondria. Importantly, in MCAO mice, APC treatment extended the effective reperfusion window from 2 to 4 h, and this window was further extended to 6 h by exogenously expressing PARK2. Taken together, we found that PARK2-dependent APC-induced mitophagy renders the brain resistant to ischemic injury. APC treatment could be a favorable strategy to extend the thrombolytic time window for stroke therapy.

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“…Overexpression of monocarboxylate transporters, which enhances the uptake of lactate for neurons, reduces infarct brain volumes . Our previous studies also showed that acidic preconditioning and postconditioning protect against the neuronal death in a variety of ischemia models . Therefore, the contributions of lactic acid to ischemic brains are controversial and it is unknown whether GPR81 activation by accumulated lactate during ischemia is involved in ischemic injury.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of G Protein‐Coupled Receptor 81 (GPR81) Protects Against Ischemic Brain Injury

et al. 2014

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Acidic preconditioning protects against ischemia-induced brain injury

Cited by 19 publications

References 27 publications

Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury

Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury

PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window

Inhibition of G Protein‐Coupled Receptor 81 (GPR81) Protects Against Ischemic Brain Injury

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