The renin‐angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis

Abstract

SUMMARYPurpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor κB (NFκB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control.

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

“…Originally described in the hypothalamus related to the control of fluid intake [237], the RAS has also been identified in other brain regions, too, including the cortex and the hippocampus [238][239][240]. Furthermore, the levels of components of the RAS were changed in the hippocampus following pilocarpine treatment of rats [241] and audiogenic seizures [242] as well as in human temporal lobe epilepsy [243]. Initial studies of a research group suggested anti-convulsant actions of Ang peptides against pentylenetetrazol-induced seizures [244] reviewed recently [245].…”

“…AT4 is the most abundant in the cortex and the hippocampus [236]. Elevated mRNA expression was shown for AT1 but not for AT2 following audiogenic seizures [242] and in temporal lobe epilepsy [243], while no data are available for AT4. Furthermore, specific AT1 antagonists had anti-convulsant properties in animal models of epilepsy [242,[248][249][250].…”

Antiepileptogenic and neuroprotective effects of losartan in kainate model of temporal lobe epilepsy

“…The repetitive seizures induced in an experimental model of TLE caused an up-regulation of the AT 1 receptor expression in the hippocampus of Wistar audiogenic rats (Pereira et al, 2010). Clinical data have also demonstrated an up-regulation of АТ 1 receptors and their mRNA expression in cortex and hippocampus of patients diagnosed with TLE (Argañaraz et al, 2008). Recently, we have demonstrated that repetitive treatment with the selective AT 1 receptor antagonist losartan is able to attenuate PTZ seizures in rats , while its chronic infusion suppresses KAinduced oxidative stress and neurotoxicity in the hippocampus during SE (Tchekalarova et al, 2014).…”

“…In view of the facts that AT 1 receptor antagonists are broadly used in clinics as a treatment for hypertension and accumulated evidence about their effects on seizure susceptibility including SE (Argañaraz et al, 2008;Pereira et al, 2010), the major rationale of this study is to evaluate the efficacy of the selective AT 1 receptor antagonist losartan, against the deleterious consequences of KA-induced SE and the associated longterm behavioral abnormalities, diurnal disturbances, biochemical changes and neuronal damage in Wistar rats.…”

Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions

“…55,56 In more specific terms, upregulation of AT1R, and its mRNA expression in rat hippocampus and cortex, has been found in patients with temporal lobe epilepsy (TLE), whereas an increased expression of AT2R was seen only in the hippocampus without alteration in its mRNA levels. 57 Ang IV analogues can be used for ameliorating the defects associated with TLE, i.e. dysfunctioning in metabolism of neurons, which is facilitated by neuronal glucose uptake through the glucose GLUT4.…”