Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice.
The possible neuroprotective effect of progesterone, a steroid hormone, on acute phase changes in a mouse model of cerebral ischaemia induced by bilateral common carotid artery occlusion (BCAO) was studied. A total of 72 male mice were included in the study. The BCAO model was used to induce partial global cerebral ischaemia. Morphological assessment included measurement of infarct size and brain oedema. Post-ischaemic seizure susceptibility was assessed using a subconvulsive dose of pentylenetetrazole (30 mgkg(-1) i.p.). Biochemical estimations included tumour necrosis factor alpha (TNF-alpha) levels and enzyme parameters such as lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase, and protein estimation. BCAO induced a significant infarct size and oedema in the saline-treated control group, along with an increase in oxidative stress, indicated by increased lipid peroxidation and decreased levels of antioxidants such as superoxide dismutase, catalase and glutathione peroxidase. Progesterone (15 mgkg(-1) i.p.) administration showed a neuro-protective effect by significantly reducing the cerebral infarct size as compared with the control group. Post-ischaemic seizure susceptibility was also reduced as the number of positive responders decreased. Brain oedema subsided, but not significantly. Progesterone significantly reduced TNF-alpha levels compared with the ischaemia group. Progesterone improved levels of all the antioxidants, indicating activity against oxidative stress induced by BCAO. The results demonstrate the neuroprotective effect of progesterone against ischaemic insult, suggesting a role for the steroid as a neuroprotective agent.
Aggarwal
Raman
R
Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Medhi
Bikash
B
Pathak
Ashis
A
Dhawan
Veena
V
Chakrabarti
Amitava
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D011372:Progestins; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone