Neuroprotective effect of postischemic administration of progesterone in spontaneously hypertensive rats with focal cerebral ischemia.
OBJECTIVE
Exogenous progesterone has been shown to reduce brain edema and ischemia-induced cell damage and to improve physiological and neurological function during the early stage of focal cerebral ischemia. In the present study, the authors assessed the neuroprotective potential of progesterone during the late stage of ischemia in a transient middle cerebral artery (MCA) occlusion model in the rat.


METHODS
Forty-eight male spontaneously hypertensive rats were randomly assigned to six groups. Progesterone was dissolved in dimethyl sulfoxide (DMSO). In four groups of rats, the dissolved progesterone (4 mg/kg or 8 mg/kg) was administered for 2 or 7 days after ischemia. In two control groups DMSO was administered for 2 or 7 days after ischemia. Occlusion of the MCA was induced by insertion of an intraluminal suture, and reperfusion was accomplished by withdrawal of the suture. Treatment was initiated on reperfusion, which followed 2 hours of MCA occlusion, and continued once a day. Lesion volume, neurological deficit, and body weight loss were measured 2 or 7 days after ischemia, depending on the animal group. Treatment with a high dose of progesterone (8 mg/kg) resulted in reductions in lesion size, neurological deficits, and body weight, compared with control rats.


CONCLUSIONS
Administration of progesterone to male rats 2 hours after MCA occlusion reduces ischemic brain damage and improves neurological deficit even 7 days after ischemia.
Kumon
Y
Y
Department of Neurosurgery, The University of Oklahoma Health Sciences Center, Oklahoma City, USA. ykumon@m.ehime-u.ac.jp
Kim
S C
SC
Tompkins
P
P
Stevens
A
A
Sakaki
S
S
Loftus
C M
CM
D000704:Analysis of Variance; D000818:Animals; D001929:Brain Edema / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000502:physiology; D004121:Dimethyl Sulfoxide; D005500:Follow-Up Studies; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014677:Pharmaceutical Vehicles; D011374:Progesterone / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D015424:Reperfusion; D013537:Sutures; D015431:Weight Loss
D018696:Neuroprotective Agents; D014677:Pharmaceutical Vehicles; D011374:Progesterone; D004121:Dimethyl Sulfoxide