17β-Estradiol Protects 7-Day Old Rats From Acute Brain Injury and Reduces the Number of Apoptotic Cells

Objective: To test a possible neuroprotective activity of 17β-estradiol in the neonatal rat brain exposed to hypoxic-ischemia (controlled hypoxia after unilateral carotid artery ligation). Methods: Seven-day-old Wistar rats underwent ligation of the left common carotid artery followed by 80 minutes hypoxia in 8% oxygen inducing an ipsilateral brain damage. Seven days later (d14), brains were analyzed quantitatively using a macroscopic and microscopic score for structural damage, hemisphere volumes were calculated, and immunohistochemistry for cleaved-caspase-3 (marker for apoptotic cells) was performed. Animals from the study group (n = 19) received 17β-estradiol (0.05 µg/g  body weight intraperitoneally) before (−64, −40, and –16 hours) and after (+3 hours) the hypoxia (hour 0: start of the hypoxia) and the control group (n = 21) received mock treatment. Results: Of the 21 pups, 13 in the NaCl group had macroscopically a severe brain damage and 7 of 19 animals in the study group encountered only discrete to mild lesions. Microscopic brain damage in the study group was significantly lower (score 1.5 ± 0.7 vs 2.8 ± 0.8, P < .05). The determined volumes of the affected hemisphere were significantly lower in the NaCl group than in the treatment group. The numbers of apoptotic cells in both hemispheres was equal in the estradiol group, but in the control group, there were significantly more apoptotic cells in the affected hemisphere (control group: ipsilateral: 1435 ± 653 vs contralateral: 143 ± 57 cells, P < .05). Discussion: 17β-Estradiol protects newborn rat brains from hypoxic–ischemic injury, in terms of both microscopic cell injury and apoptosis.