Effects of progesterone administration on infarct volume and functional deficits following permanent focal cerebral ischemia in rats

Abstract

Recent experimental evidence indicates that progesterone (PROG) protects against various models of brain injury, including ischemic stroke. Most human studies of pharmacologic treatments for acute cerebral stroke have failed despite initial success in animal models. To simulate better the typical human stroke without reperfusion, the present study was conducted to examine the efficacy of PROG on infarct volume and functional outcome in a permanent model of stroke, using direct cauterization of the middle cerebral artery (MCA). Twenty-four male adult Sprague-Dawley rats underwent pMCAO by electro-coagulation and sham operation. After induction of permanent MCA occlusion (pMCAO), the rats received an initial intraperitoneal injection of PROG (8 mg/kg) or vehicle at 1h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h. Functional deficits were tested on the rotarod and grip strength meter at 24, 48 and 72 h after pMCAO. The rats were killed 72 h after surgery and isolated brain was sectioned into coronal slices and stained with 2, 3, 5-triphenyltetrazolium chloride (TTC). PROG-treated rats showed a substantial reduction (54.05%) in the volume of the infarct (% contralateral hemisphere) compared to vehicle controls. In addition there was a significant improvement in ability to remain on an accelerating rotarod and increased grip strength observed in the pMCAO rats treated with PROG compared to vehicle. Taken together, these data indicate that PROG is beneficial in one of the best-characterized models of stroke, and may warrant further testing in future clinical trials for human stroke.

Progesterone Inhibits the Growth of Human Neuroblastoma: In Vitro and In Vivo Evidence

“…We selected the high P4 doses on the basis of our in vitro data and our previous reports that P4 is neuroprotective at lower doses (8 and 16 mg/kg) against traumatic brain injury and stroke (24)(25)(26). In the current experiment, we found a potent inhibitory effect of high-dose P4 on neuroblastoma tumor growth in nude In a comparative study, Wiehle et al (27) tested RU486, P4 and CDB-4124 (nor-progestin) against mammary tumors in vivo and observed that P4 treatment at 10 mg/kg for 28 days increased the size and number of tumors in female rats.…”

Progesterone inhibits inflammatory response pathways after permanent middle cerebral artery occlusion in rats

“…PROG was dissolved in 22.5% 2-hydroxypropyl-β-cyclodextrin, and the rats received an initial intraperitoneal injection of PROG (8 mg/kg) at 1 h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h (13,14). In the vehicle-treated group, PROG was replaced by 2-hydroxypropyl-β-cyclodextrin in the same volume.…”

“…PROG has been shown to display neuroprotective properties following cerebral ischemia, decreasing lesion volume and improving functional recovery (14,19,13). Both cell survival and neuronal density are improved by acute or chronic PROG treatment in male (19) and female (20) animals.…”

Progesterone Treatment for Experimental Stroke: An Individual Animal Meta-Analysis

“…[4][5][6][7][8][9][10][11][12][13][14] Progesterone has already been shown to be safe and effective for several clinical applications, e.g., hormone replacement therapy, and a variety of preparations are available for different modes of administration. 15 Furthermore, no severe adverse effects have been reported even when progesterone was used at high dose.…”