Neuroprotection by progesterone after transient cerebral ischemia in stroke-prone spontaneously hypertensive rats.
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.
Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: syousu2@emory.edu.
Seema
S
Yousuf
Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: fatif@emory.edu.
Fahim
F
Atif
Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: isayeed@emory.edu.
Iqbal
I
Sayeed
Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: jwang26@emory.edu.
Jun
J
Wang
Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: dstein04@emory.edu.
Donald G
DG
Stein
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; D011374:Progesterone
Functional recovery; Neuroprotection; Progesterone; Stroke-prone spontaneously hypertensive rats (SHRSP); Transient cerebral ischemia