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Advanced Neurology Losartan and Enalapril in SE

with epilepsy could experience recurring episodes of in lithium-pilocarpine (LiP)-induced status epilepticus (SE)
catecholamine surge after each seizure, potentially leading in rats. LiP-induced seizure animal model is an epilepsy
to a risk of postictal catecholamine surge and subsequent model that replicates human temporal lobe epilepsy. Akin
myocardial dysfunction . In addition, cardiac changes to human SE, in LiP-induced SE, after the administration
[2]
in animals with chronic or acute seizures have been of pilocarpine, the animals undergo an initial phase of SE,
investigated in a few experimental studies [3,4] . In rats, which is followed by a latent (seizure-free) interval that
[12]
deaths associated with acute seizures were attributed causes repeated spontaneous seizures to occur . Therefore,
to autonomically mediated asystole, which was further this particular model can potentially model myriad
accompanied by hypoxemia . According to Naggar et al., clinical scenarios, namely the effect of pre-treatment with
[5]
cardiac changes accompany epilepsy, leading to a significant RAS modulators on SE, effect on spontaneous convulsive
decrease in cardiac performance . seizures (SCS) or epileptogenesis, the impact on seizure-
[6]
related cardiovascular changes. The effects on incidence,
The renin-angiotensin system (RAS) plays a role in
regulating arterial pressure and maintaining volume development and extent of SE, occurrence of SCS, survival,
and cardiac changes were evaluated.
balance in mammals. This is achieved through the action
of the vasoactive peptide angiotensin II (Ang II) and its 2. Materials and methods
interaction with angiotensin II type 1 receptors (AT1Rs). 2.1. Experimental animals
While the individual components of the RAS system have
not been identified in the brain, it is widely accepted that a The approval from the Institutional Animal Ethics
brain RAS exists. Experimental studies have demonstrated Committee (IAEC), All India Institute of Medical Sciences
the involvement of Ang II and AT1Rs in the regulation of (AIIMS), New Delhi, India, was obtained before carrying out
seizure susceptibility in various epilepsy models. A study the experiments (ethics approval no. 885/IAEC/15). For this
conducted on patients with temporal lobe epilepsy study, male rats, Wistar strain, weighing 150 – 250 g were
resulting from mesial temporal sclerosis aimed to identify used. The rats utilized in the study were acquired from the
and measure the levels of Ang II AT1 and AT2 receptors Central Animal Facility situated at AIIMS in New Delhi,
in the cortex and hippocampus. The study found that the India. These rats were housed in departmental animal houses,
messenger ribonucleic acid (mRNA) expression of the which contained polypropylene cages filled with paddy husk.
Ang II AT1 receptor was elevated compared to control They were kept in groups of three at a temperature ranging
groups . In a study using a genetically based model, Wistar between 22 and 25°C, following a 12-h light/dark cycle.
[7]
audiogenic rats (WARs) and Wistar rats were examined, In addition, they were provided with unrestricted access
and no intrinsic changes in the angiotensin-converting to rat pellet food produced by M/s Ashirwad Industries,
enzyme (ACE) or the AT1 receptor were found. Following Chandigarh. Before the experiment, a period of 7 days
the generation of recurrent seizures in a temporal lobe was dedicated to acclimating the rats to the laboratory
epilepsy model, the up-regulation profile for ACE and environment. All experimental procedures strictly adhered
AT1 receptor expression in the hippocampus of WARs was to the Animal Research Reporting of In Vivo Experiments
[8]
identified . As a result, medications that modulate RAS are guidelines and the Indian National Science Academy criteria
known to be beneficial in suppressing seizures in animal for the treatment and usage of animals in scientific research.
studies. Chronic seizures also upregulate the brain RAS [7-10] . 2.2. Drugs
The cardiovascular component in seizure-related mortality
suggests the need for a comprehensive evaluation of RAS in We obtained LOS, ENP, lithium chloride, and pilocarpine
seizure control and seizure-related cardiovascular risk due from Sigma Aldrich (USA). The diazepam, phenobarbitone,
to its favorable cardiovascular activity. and atenolol (AT) were obtained from Cipla Limited
(India), Ranbaxy Laboratories (India), and Samarth Life
Normally, two strategies are employed for modulating Sciences (India). All drug solutions were prepared freshly
RAS, either by blocking the angiotensin receptor type I in normal saline before use, except for diazepam which
using drugs like losartan (LOS) or by inhibiting the ACE was suspended in 8% Tween 20. The concentration of all
using agents like enalapril (ENP). In a rat Pentylenetetrazole the drugs administered in rats was similar, i.e., X/2 mg/mL,
(PTZ) kindling model, we previously showed that neither where X is the dose of the drug in mg/kg. Administered
ENP nor LOS is likely to vitiate seizure control with sodium volume was between 0.3 and 0.5 mL.
valproate; both drugs prevent negative cognitive sequelae
due to valproate . 2.3. Experimental protocols
[11]
The present study was designed to investigate the effects of Two different experimental protocols were used. In the
angiotensin receptor blocker (LOS) and ACE inhibitor (ENP) first set of experiments based on pre-SE protocol, the rats

Volume 2 Issue 2 (2023) 2 https://doi.org/10.36922/an.0387