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Advanced Neurology Losartan and Enalapril in SE

were divided into treatment groups, and administration cannulas following SE, and this process was repeated twice
of ENP (20 mg/kg, i.p.), LOS (10 mg/kg, i.p.) and AT daily from day 1 to day 3.
(50 mg/kg, p.o.) were started 45 min before for ENP
and 120 min before for both LOS and AT before lithium 2.4.1. Analysis of SCS
administration and were carried out for 7 days’ post- The recorded videos were examined by two separate
pilocarpine . Each treatment group comprised 8 rats and observers using a VLC media player, with a playback speed
[11]
an equal number of rats, i.e., 8, were assigned to the model of 4× – 6×. During the analysis, the observers recorded the
control group, which was given LiP only. In this design, the onset, frequency, and duration of spontaneous convulsive
effect of the above-mentioned drugs on the induction of SE seizure (SCS). Only forelimb clonus (FLC) or generalized
as well as progression to SCS and survival was evaluated. tonic clonic seizures (GTCS) were taken into consideration
In another set of experiments based on post-SE for the SCS evaluation since they have a distinct beginning
protocol, 27 rats exhibiting SE after lithium and pilocarpine and end.
administration were randomized into control (n = 9) and 2.5. Effect on body weight
treatment groups, i.e., LOS (10 mg/kg, i.p., n = 9) and
AT (50 mg/kg, p.o., n = 9), using block randomization SE results in a characteristic decrease in body weight and
technique in order to reduce baseline differences between several days are required to gain baseline body weight
them. For 7 days following pilocarpine administration, (body weight before SE) [16] . All rats were weighed every
post-treatment was carried out each day at the same day to determine the change in body weight. Due to
time to determine the effect of drug treatment on SCS, variations in body weights at baseline, which ranged
survival, body weight, and cardiac parameters, namely from 150 to 250 g, the percentage change in body
echocardiography, histopathology, and heart weight/body weight was determined by setting the initial weight on
weight ratios. As ENP treatment was associated with a very day 0 as 100%.
high mortality in pilot studies, ENP post-treatment group 2.6. Effect on cardiovascular parameters
was not included. The rats administered with lithium
and pilocarpine but that did not show any SE served as 2.6.1. Echocardiographic analysis
controls and were similarly randomized into LiP control Echocardiography was performed on the rats following
(n = 8), LOS- (n = 8), and AT-treated (n = 8) groups and the method described by Jaiswal et al. To briefly
[17]
administered with the respective drug. outline the process, rats were anesthetized with
ketamine (75 mg/kg, i.p.), their chest hairs were clipped,
2.4. Induction of SE and they were positioned supine for examination.
LiP model that we standardized previously was used A transducer probe was gently placed on the left parasternal
to induce SE . To provide a brief overview, rats pre- position. Two-dimensional M-mode echocardiography
[12]
treated with lithium chloride (127 mg/kg, i.p., day-1) for was conducted using a 12 MHz neonatal cardiac probe
24 h were subsequently administered with pilocarpine transducer with a high frame rate and shallow focus
at a dose of 30 mg/kg on day 0. To decrease peripheral (10–25 mm). The imaging was performed from a short-
secretions, glycopyrrolate was injected subcutaneously at axis view at the level of the papillary muscles of the left
a dosage of 0.02 mg/kg, 30 min before the administration ventricle. A fully digitized Phillips ultrasound machine
of pilocarpine. Once 90 min had passed since the onset (HD11XE) was utilized for this purpose. The resulting
of SE, a combination of diazepam (15 mg/kg, i.p.) and images, consisting of five to nine consecutive heart cycles,
phenobarbitone (25 mg/kg, i.p., administered 10 min were transferred online for analysis. An analyst, who was
after diazepam) was introduced to bring an end to the unaware of the different treatment groups, performed the
SE. The rats were then housed individually in plexiglass analysis. Three representative cycles were evaluated and
cages and video-monitored for 10 h each day (8:00 AM to data therefrom were averaged for the following parameters:
6:00 PM) for 18 days’ post-SE for the occurrence of SCS. Interventricular septal end diastole, left ventricular internal
Studies on rodent species have indicated that seizures are diameter end diastole, left ventricular posterior wall end
more frequent during the light phase of a 12-h dark/light diastole, fractional shortening, stroke volume, and left
cycle, as opposed to the nocturnal period [13,14] , and video- ventricular internal diameter systole.
electroencephalography recordings have demonstrated
that approximately 67% of daily seizures take place during 2.6.2. Heart weight/body weight ratio
the light phase of the cycle , therefore, video recording On the day of the sacrifice, the rats were weighed, and their
[15]
of seizures was done in the daytime. In all rats, dextrose hearts were removed while they were under pentobarbitone
normal saline was administered through oral feeding anesthesia (50 mg/kg, i.p.). The extracted hearts were then

Volume 2 Issue 2 (2023) 3 https://doi.org/10.36922/an.0387