AbstractsBiology & Animal Science

Expression of angiotensin receptors in the rat brain after focal cerebral ischemia

by Nadezhda Gerova

Institution: Freie Universität Berlin
Degree: PhD
Year: 2015
Record ID: 1111210
Full text PDF: http://edocs.fu-berlin.de/diss/receive/FUDISS_thesis_000000098454


The Renin-Angiotensin System (RAS) is well known for its function as a regulator of blood pressure and fluid and electrolyte balance with its major effective peptide Angiotensin II. Beside the systemic RAS, a lot of other tissues such as the heart, lungs, liver and the blood vessels have been shown to produce Ang II. The RAS was first known to act only in the periphery. Later RAS and its components were found in the brain and appeared to be autonomous. The development of selective receptor antagonists led to the discovery of the angiotensin receptors. Among these, the AT1 and AT2 receptor subtypes seem to play an important role in ischemic processes. The numerous studies of angiotensin receptors in the last two decades showed that the AT1 receptor was found to be abundant in the mature brain while the AT2 receptor was highly expressed before and during the neonatal period and its expression decreased speedily afterwards. Therefore the AT1 receptor has been studied profusely while much less was known about the AT2 receptor. The majority of the studies were done in vitro. So our aim was to show the distribution of the two receptors in vivo as well as to identify the cells of expression and possible correlations with the apoptosis and inflammation following cerebral ischemia. Using the method of transient MCAO we induced a 90 min focal cerebral ischemia in the right cerebral hemisphere of animals from the “stroke group”, while the “sham” animals underwent only a superficial skin surgery. Then performing immunohistological, fluorescent, molecular and proteinbiochemical methods we were able to show significant differences. First, we found that there was an upregulation of AT2 receptor expression in the ischemic brain hemisphere, especially in the striatum, cerebral frontal cortex, piriform cortex and hippocampus. Second, the AT2 receptors were expressed exclusively in neurons. In our immunofluorescent stainings we were able to prove that the striatal AT2 receptor positive cells had long neurites and co-expressed MAP2 in contrast to other AT2 receptor positive neurons away from the periinfarct area. Third, there was no significant change in the expression of AT1 receptor between stroke and sham animals. Interestingly, many of the AT1 receptors were located in astrocytes and only sparsely in cortical neurons, which coincided with the in vitro results of Sumners et al. Many of the astrocytes in the periinfarct area appeared stouter, had powerful projections and were located around neuron-like cells. These „activated” astrocytes were significantly increased in number in both hemispheres when compared to the sham group (p<0.001), especially in the right hemisphere (p<0.0001). A lot of the activated astrocytes were also positive for the apoptotic marker cCasp-3, which is quite understandable, knowing that astrocytes are highly sensitive to ischemia. The significant reactive astrogliosis is supposed to have both injurious and beneficial effects on neurons. Because of the AT1 receptor localization in astrocytes, we think…