Page 122 - AN-2-2

Advanced Neurology Losartan and Enalapril in SE

AT when given in combination with levetiracetam kainite-induced SE, observed in both normotensive and
(β blocker + antiseizure) not only resulted in a reduction spontaneously hypertensive rats [34,35] . Sun et al. reported
1
of seizures and complete prevention of respiratory arrest that the protein expression of angiotensin II and AT1
but also contributed to a 100% enhancement in survival was increased following SE in LiP model . Gomes et al.
[36]
rate . In another research endeavor, pre-administration have shown a significant reduction in spontaneous motor
[28]
of AT proved to be effective in mitigating the development seizures and improvement in behavioral and biochemical
of seizure progression within the 120–180-min timeframe parameters after angiotensin (1-7) in the pilocarpine
after kainic acid exposure, leading to a noteworthy 32% model, which along with this study, corroborates the role
decrease in the cumulative score compared to the kainic acid of RAS in epilepsy .
[37]
control group . Co-administration of AT and diazepam Since rats were hyperactive, we did not record blood
[29]
reduced seizure behavior and provided cardioprotection, pressure but instead, we carried out echocardiography.
while diazepam when given alone only provided seizure However, there was no noticeable or substantial alteration
prevention but not cardioprotection . Besides AT, the observed. In the study conducted by Naggar et al. , chronic
[30]
[6]
rats which did not show any SE after LiP administration seizures were induced in Sprague–Dawley rats using kainic
were also randomized to treatment groups similar to those acid. The findings revealed a decrease in vagal tone, an increase
showing SE and followed up as drug controls. No mortality in QT dispersion, and eccentric cardiac hypertrophy, while
or SCS were observed in these groups.
no significant cardiac fibrosis was observed. These effects
The pre-treatment and post-treatment protocols had were consistent at both the 2 – 3 months and 7 – 11 months
opposite effects on the onset of SCS. However, all drugs duration following kainic acid injection . They concluded
[6]
used suppressed the number as well as the duration that epilepsy is accompanied by cardiac changes that can
of SCS in both protocols. The enhanced activation of have significant impacts on seizure-associated cardiac
oxidative stress, apoptosis, and neuroinflammation, performance. No significant changes in echocardiography
leading to neurodegeneration in various brain disorders, in the present study may be due to methodological
is strongly associated with the overexpression of brain differences in the two studies, and echocardiography could
ACE, Ang II, and AT1Rs. The potent neuroprotective be repeated only for surviving rats. In our study, histological
effects of inhibiting AT1R in certain brain diseases have assessment using H&E staining did show some ischemic
been consistently demonstrated in numerous studies. The and inflammatory changes after SE which were not present
ACE2/Angiotensin (1-7)/Mas receptor (MASR) axis in the in drug-treated groups.
brain acts as another RAS pathway that counterbalances An interesting finding with regard to cardiovascular
the negative effects of the ACE/Ang II/AT1R axis on brain changes is a significantly increased heart weight/body
neurons . The ineffectiveness of ENP in halting seizures weight ratio for rats that died during the study. Increased
[31]
is likely attributed to the inhibition of Ang I to Ang II heart weight, both wet and dry, was reported after 8 – 12 days
conversion by ACE inhibitors, which disrupts both the of LiP-induced SE in rats . In a human investigation,
[38]
neuroprotective and neurodegenerative pathways. This is cardiac hypertrophy was identified in eight out of ten
not the case with AT1Rs blockers, which simply obstruct
the neurodegenerative route and might have demonstrated patients who underwent autopsy after succumbing to
[39]
more protective effects than ENP. In earlier reports, the an episode of SE . Melenovsky et al. have put forth the
effect of LOS and ENP in preventing seizures varies argument, in the context of a volume overload heart failure
depending on the seizure model. Thus, where seizures were model, that an increase in heart weight is associated with
heightened mortality, and a notable proportion of animals
induced by acoustic stimulation, both LOS and ENP were experience abrupt, unexpected death rather than a gradual
found to be effective in decreasing the seizure severity , progression towards heart failure .
[8]
[40]
while both LOS and ENP were found to be ineffective
against PTZ-induced convulsions . In particular, ENP Logically, for a parameter such as heart weight/body
[32]
is ineffective in decreasing seizure severity [11,33] . However, weight ratio, alterations in either measure may potentially
there have been reports of a promising outcome where ENP impact results. Daily body weight records reveal that all rats
demonstrated an enhancing effect on the anticonvulsant experiencing SE had a significant decrease in body weight
properties of lamotrigine in the maximal electroshock for the first few days after which only the surviving rats
epilepsy model . In studies with SE models, Tchekalarova tended to recover their baseline weights. The recovery was
[10]
et al. observed that the blockade of AT1 receptors in maximum for LOS-treated rats and significantly less for
spontaneously hypertensive rats effectively delayed the AT-treated and untreated groups; AT-treated rats showed
onset of seizures, while also reducing their frequency and significantly lower body weights throughout the study.
duration during and after treatment discontinuation in A similar 10 – 20% body weight decrease that returned to

Volume 2 Issue 2 (2023) 8 https://doi.org/10.36922/an.0387