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Neuroprotection by progesterone after transient cerebral ischemia in stroke-prone spontaneously hypertensive rats.
Horm Behav. 2016 08; 84:29-40.HB

Abstract

We investigated the neuroprotective effects of progesterone (P4) treatment in stroke-prone spontaneously hypertensive rats (SHRSPs) given 60-min transient middle cerebral artery occlusion (tMCAO). The treatment groups were: (1) Wistar-Kyoto (normotensive sham), (2) SHRSP (hypertensive sham), (3) tMCAO SHRSPs (SHRSP+tMCAO), and (4) SHRSP+tMCAO+P4. P4 (8mg/kg) was administered 1h after occlusion and then daily for 14days. We measured cerebral infarction volume, blood pressure and body weight. Behavioral outcomes were analyzed at post-stroke days 3, 9, and 14. To assess morphological protection we measured activation of microglia and astrocytes, oxidative stress, apoptosis, expression of vascular endothelial growth factor (VEGF), an angiogenic marker, and IL-1β, a marker of inflammation, on day 14 post-stroke. There was no effect of P4 on body weight or systolic blood pressure compared to the SHRSP+tMCAO group. However, grip strength and sensory neglect measures in the P4 group were improved compared to SHRSP+tMCAO. In addition, significantly larger infarct volumes were seen in the SHRSP+tMCAO group compared to SHRSP+tMCAO+P4. Increased markers of the injury cascade such as macrophages, activated astrocytes, superoxide anion and apoptotic cells observed in the SHRSP+tMCAO group were significantly decreased by P4. We conclude that, despite hypertensive comorbidity, P4 improves functional outcomes and attenuates stroke infarct in hypertensive rats by reducing superoxide anion expression and by decreasing inflammation and neuronal apoptosis.

Authors+Show Affiliations

Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: syousu2@emory.edu.Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: fatif@emory.edu.Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: isayeed@emory.edu.Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: jwang26@emory.edu.Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: dstein04@emory.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27283379

Citation

Yousuf, Seema, et al. "Neuroprotection By Progesterone After Transient Cerebral Ischemia in Stroke-prone Spontaneously Hypertensive Rats." Hormones and Behavior, vol. 84, 2016, pp. 29-40.
Yousuf S, Atif F, Sayeed I, et al. Neuroprotection by progesterone after transient cerebral ischemia in stroke-prone spontaneously hypertensive rats. Horm Behav. 2016;84:29-40.
Yousuf, S., Atif, F., Sayeed, I., Wang, J., & Stein, D. G. (2016). Neuroprotection by progesterone after transient cerebral ischemia in stroke-prone spontaneously hypertensive rats. Hormones and Behavior, 84, 29-40. https://doi.org/10.1016/j.yhbeh.2016.06.002
Yousuf S, et al. Neuroprotection By Progesterone After Transient Cerebral Ischemia in Stroke-prone Spontaneously Hypertensive Rats. Horm Behav. 2016;84:29-40. PubMed PMID: 27283379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection by progesterone after transient cerebral ischemia in stroke-prone spontaneously hypertensive rats. AU - Yousuf,Seema, AU - Atif,Fahim, AU - Sayeed,Iqbal, AU - Wang,Jun, AU - Stein,Donald G, Y1 - 2016/06/06/ PY - 2015/10/15/received PY - 2016/04/11/revised PY - 2016/06/04/accepted PY - 2016/6/11/entrez PY - 2016/6/11/pubmed PY - 2017/10/4/medline KW - Functional recovery KW - Neuroprotection KW - Progesterone KW - Stroke-prone spontaneously hypertensive rats (SHRSP) KW - Transient cerebral ischemia SP - 29 EP - 40 JF - Hormones and behavior JO - Horm Behav VL - 84 N2 - We investigated the neuroprotective effects of progesterone (P4) treatment in stroke-prone spontaneously hypertensive rats (SHRSPs) given 60-min transient middle cerebral artery occlusion (tMCAO). The treatment groups were: (1) Wistar-Kyoto (normotensive sham), (2) SHRSP (hypertensive sham), (3) tMCAO SHRSPs (SHRSP+tMCAO), and (4) SHRSP+tMCAO+P4. P4 (8mg/kg) was administered 1h after occlusion and then daily for 14days. We measured cerebral infarction volume, blood pressure and body weight. Behavioral outcomes were analyzed at post-stroke days 3, 9, and 14. To assess morphological protection we measured activation of microglia and astrocytes, oxidative stress, apoptosis, expression of vascular endothelial growth factor (VEGF), an angiogenic marker, and IL-1β, a marker of inflammation, on day 14 post-stroke. There was no effect of P4 on body weight or systolic blood pressure compared to the SHRSP+tMCAO group. However, grip strength and sensory neglect measures in the P4 group were improved compared to SHRSP+tMCAO. In addition, significantly larger infarct volumes were seen in the SHRSP+tMCAO group compared to SHRSP+tMCAO+P4. Increased markers of the injury cascade such as macrophages, activated astrocytes, superoxide anion and apoptotic cells observed in the SHRSP+tMCAO group were significantly decreased by P4. We conclude that, despite hypertensive comorbidity, P4 improves functional outcomes and attenuates stroke infarct in hypertensive rats by reducing superoxide anion expression and by decreasing inflammation and neuronal apoptosis. SN - 1095-6867 UR - https://www.unboundmedicine.com/medline/citation/27283379/Neuroprotection_by_progesterone_after_transient_cerebral_ischemia_in_stroke_prone_spontaneously_hypertensive_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0018-506X(15)30114-8 DB - PRIME DP - Unbound Medicine ER -