Renin-Angiotensin System Modulation in Epilepsy Management

The renin–angiotensin system (RAS) is increasingly recognised as a key regulator of neuronal excitability, neuroinflammation and blood–brain barrier integrity in epilepsy. Beyond its classical role in cardiovascular homeostasis, RAS components are expressed throughout the central nervous system, where they influence glial activation, oxidative stress and synaptic remodelling. The system comprises two opposing axes: the ACE–Ang II–AT₁R pathway, which tends to promote inflammation and seizure susceptibility, and the ACE2–Ang-(1-7)–MasR axis, which exerts antiinflammatory and neuroprotective actions. Preclinical studies have shown that RAS modulation can reduce seizure frequency, attenuate hippocampal damage and improve cognitive outcomes, either alone or in conjunction with established antiepileptic drugs. Genetic polymorphisms in RAS‐related genes further point to individual variability in treatment response, opening avenues for personalised therapeutic strategies. Overall, targeting RAS offers a promising multipronged approach to both seizure control and the prevention of disease progression.

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Renin-Angiotensin System Modulation in Epilepsy Management publication trend

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Technical terms

Renin–Angiotensin System: Hormonal cascade regulating blood pressure, fluid balance and modulating neuroinflammatory and excitability pathways in the brain.

Angiotensin-Converting Enzyme: Key enzyme converting angiotensin I to angiotensin II, the main effector peptide of the classical RAS axis.

Angiotensin II Type 1 Receptor (AT1R): G protein–coupled receptor mediating the proinflammatory and proconvulsant actions of angiotensin II.

Angiotensin-(1-7): Heptapeptide of the protective RAS axis that binds the Mas receptor to exert antiinflammatory and neuroprotective effects.

Epileptogenesis: Process by which a normal brain develops a persistent predisposition to generate epileptic seizures.

References

1. Captopril alleviates epilepsy and cognitive impairment by attenuation of C3-mediated inflammation and synaptic phagocytosis. Journal of Neuroinflammation (2022).
2. Antiepileptic effects of long-term intracerebroventricular infusion of angiotensin-(1-7) in an animal model of temporal lobe epilepsy.. Clinical Science (2020).
3. Role of the Angiotensin Pathway and its Target Therapy in Epilepsy Management. International Journal of Molecular Sciences (2019).