Aromatase and neuroinflammation in rat focal brain ischemia. Issue 174 (November 2017)

• Record Type: Journal Article
• Authors: Zhong, Yu H.; Dhawan, Jasbeer; Kovoor, Joel A.; Sullivan, John; Zhang, Wei X.; Choi, Dennis; Biegon, Anat
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 174(2017)
• Page Start: 225
• Page End: 233
• Publication Date: 2017-11
• Subjects: MCAO middle cerebral artery occlusion -- NMDA N-methyl-d-aspartic acid -- tPA tissue plasminogen activator -- WEST Women Estrogen Stroke Trial -- TSPO translocator protein -- TPEN N, N, Nʹ, Nʹ-tetrakis (2-pyridylmethyl) ethylenediamine -- CCA common carotid artery -- ECA external carotid artery -- ICA internal carotid artery -- MCA middle cerebral artery -- PCA posterior cerebral artery -- DMSO dimethyl sulfoxide -- PAP Peroxidase Antiperoxidase -- PBS phosphate buffer saline -- TBS Tris- Buffer saline; Aromatase -- Neuroinflammation -- Stroke -- Male rat; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2017.09.019
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Aromatase expression around the infarct was increased in male rats 2 weeks after middle cerebral artery occlusion. Intense and wide spread neuroinflammation was evident in the same animals. Aromatase expression did not correlate with infarct size. Aromatase expression and neuroinflammation demonstrated a moderate, but statistically significant, negative correlation. Abstract: Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents. Intact male rats were subjected to transient (90 min) middle cerebral artery occlusion (MCAO) and administered selfotel (N-methyl-d -aspartic acid (NMDA) receptor competitive antagonist), TPEN (a zinc chelator), a combination of the two drugs or vehicle, injected immediately after reperfusion. Animals were killed 14 days after MCAO and consecutive brain sections used to measure aromatase expression, cerebral infarct volume and neuroinflammation. Quantitative immunohistochemistry (IHC) demonstrated increased brain aromatase expression in the peri-infarct area relative to contralesional area, which was partially abrogated by neuroprotective agents. There was no correlation between aromatase expression in the peri-infarct zone and infarct volume, which was reduced by neuroprotective agents. Microglial activation, measured by quantitative autoradiography, was positively correlated with infarct and inversely correlated with aromatase expression in the peri-infarct zone. Our findings indicate that focal ischemia upregulates brain aromatase in the male rat brain at 14 days post surgery, which is within the time frame documented in females. However, the lack of negative correlation between aromatase expression and infarct volume and lack of positive correlation between microgliosis and aromatase do not support a major role for aromatase as a mediator of neuroprotection or a causal relationship between microglial activation and increased aromatase expression in male focal ischemia.