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Dihydrocapsaicin (DHC) enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat.
Brain Res. 2017 Sep 15; 1671:18-25.BR

Abstract

OBJECTIVE

Hypothermia has demonstrated neuroprotection following ischemia in preclinical studies while its clinical application is still very limited. The aim of this study was to explore whether combining local hypothermia in ischemic territory achieved by intra-arterial cold infusions (IACIs) with pharmacologically induced hypothermia enhances therapeutic outcomes, as well as the underlying mechanism.

METHODS

Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2h using intraluminal hollow filament. The ischemic rats were randomized to receive: 1) pharmacological hypothermia by intraperitoneal (i.p.) injection of dihydrocapsaicin (DHC); 2) physical hypothermia by IACIs for 10min; or 3) the combined treatments. Extent of brain injury was determined by neurological deficit, infarct volume, and apoptotic cell death at 24h and/or 7d following reperfusion. ATP and ROS levels were measured. Expression of p-Akt, cleaved Caspase-3, pro-apoptotic (AIF, Bax) and anti-apoptotic proteins (Bcl-2, Bcl-xL) was evaluated at 24h. Finally, PI3K inhibitor was used to determine the effect of p-Akt.

RESULTS

DHC or IACIs each exhibited hypothermic effect and neuroprotection in rat MCAO models. The combination of pharmacological and physical approaches led to a faster and sustained reduction in brain temperatures and improved ischemia-induced injury than either alone (P<0.01). Furthermore, the combination treatment favorably increased the expression of anti-apoptotic proteins and decreased pro-apoptotic protein levels (P<0.01 or 0.05). This neuroprotective effect was largely blocked by p-Akt inhibition, indicating a potential role of Akt pathway in this mechanism (P<0.01 or 0.05).

CONCLUSIONS

The combination approach is able to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection following ischemic stroke. The findings here move us a step closer towards translating this long recognized TH from bench to bedside.

Authors+Show Affiliations

China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing, China.Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China. Electronic address: jixm@ccmu.edu.cn.China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China; Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28684048

Citation

Wu, Di, et al. "Dihydrocapsaicin (DHC) Enhances the Hypothermia-induced Neuroprotection Following Ischemic Stroke Via PI3K/Akt Regulation in Rat." Brain Research, vol. 1671, 2017, pp. 18-25.
Wu D, Shi J, Elmadhoun O, et al. Dihydrocapsaicin (DHC) enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat. Brain Res. 2017;1671:18-25.
Wu, D., Shi, J., Elmadhoun, O., Duan, Y., An, H., Zhang, J., He, X., Meng, R., Liu, X., Ji, X., & Ding, Y. (2017). Dihydrocapsaicin (DHC) enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat. Brain Research, 1671, 18-25. https://doi.org/10.1016/j.brainres.2017.06.029
Wu D, et al. Dihydrocapsaicin (DHC) Enhances the Hypothermia-induced Neuroprotection Following Ischemic Stroke Via PI3K/Akt Regulation in Rat. Brain Res. 2017 Sep 15;1671:18-25. PubMed PMID: 28684048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydrocapsaicin (DHC) enhances the hypothermia-induced neuroprotection following ischemic stroke via PI3K/Akt regulation in rat. AU - Wu,Di, AU - Shi,Jingfei, AU - Elmadhoun,Omar, AU - Duan,Yunxia, AU - An,Hong, AU - Zhang,Jun, AU - He,Xiaoduo, AU - Meng,Ran, AU - Liu,Xiangrong, AU - Ji,Xunming, AU - Ding,Yuchuan, Y1 - 2017/07/03/ PY - 2017/06/07/received PY - 2017/06/27/revised PY - 2017/06/28/accepted PY - 2017/7/8/pubmed PY - 2018/5/18/medline PY - 2017/7/8/entrez KW - Apoptotic cell death KW - Intra-arterial cold infusions (IACIs) KW - Ischemia/reperfusion injury KW - Middle cerebral artery KW - Pharmacological hypothermia SP - 18 EP - 25 JF - Brain research JO - Brain Res. VL - 1671 N2 - OBJECTIVE: Hypothermia has demonstrated neuroprotection following ischemia in preclinical studies while its clinical application is still very limited. The aim of this study was to explore whether combining local hypothermia in ischemic territory achieved by intra-arterial cold infusions (IACIs) with pharmacologically induced hypothermia enhances therapeutic outcomes, as well as the underlying mechanism. METHODS: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2h using intraluminal hollow filament. The ischemic rats were randomized to receive: 1) pharmacological hypothermia by intraperitoneal (i.p.) injection of dihydrocapsaicin (DHC); 2) physical hypothermia by IACIs for 10min; or 3) the combined treatments. Extent of brain injury was determined by neurological deficit, infarct volume, and apoptotic cell death at 24h and/or 7d following reperfusion. ATP and ROS levels were measured. Expression of p-Akt, cleaved Caspase-3, pro-apoptotic (AIF, Bax) and anti-apoptotic proteins (Bcl-2, Bcl-xL) was evaluated at 24h. Finally, PI3K inhibitor was used to determine the effect of p-Akt. RESULTS: DHC or IACIs each exhibited hypothermic effect and neuroprotection in rat MCAO models. The combination of pharmacological and physical approaches led to a faster and sustained reduction in brain temperatures and improved ischemia-induced injury than either alone (P<0.01). Furthermore, the combination treatment favorably increased the expression of anti-apoptotic proteins and decreased pro-apoptotic protein levels (P<0.01 or 0.05). This neuroprotective effect was largely blocked by p-Akt inhibition, indicating a potential role of Akt pathway in this mechanism (P<0.01 or 0.05). CONCLUSIONS: The combination approach is able to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection following ischemic stroke. The findings here move us a step closer towards translating this long recognized TH from bench to bedside. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/28684048/Dihydrocapsaicin__DHC__enhances_the_hypothermia_induced_neuroprotection_following_ischemic_stroke_via_PI3K/Akt_regulation_in_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(17)30277-9 DB - PRIME DP - Unbound Medicine ER -