Research reportCerebral small vessel disease predisposes to temporal lobe epilepsy in spontaneously hypertensive rats

- 5-weeks-old spontaneously hypertensive rats (SHRs) have similar seizure susceptibility to control rats.
- 16-weeks-old SHRs develop amygdala kindling more rapidly (less stimulations) than control rats.
- 16-weeks-old SHRs display cerebral small vessels disease (CSVD) which is prevented by enalapril long-term treatment.
- Enalapril treatment, inhibiting the development of CSVD, normalizes amygdala kindling development in SHRs.
- CSVD in SHRs is associated with a higher susceptibility to amygdala kindling.

The link between cerebral small vessel disease (CSVD) and epilepsy has been poorly investigated. Some reports suggest that CSVD may predispose to temporal lobe epilepsy (TLE). Aim of this study was to evaluate whether spontaneously hypertensive rats (SHRs), an established model of systemic hypertension and CSVD, have a propensity to develop TLE more than generalized seizures. To this aim, amygdala kindling, as a model of TLE, and pentylenetetrazole (PTZ)-induced kindling, as a model of generalized seizures, have been used to ascertain whether SHRs are more prone to TLE as compared to Wistar Kyoto control rats. While young SHRs (without CSVD) do not differ from their age-matched controls in both models, old SHRs (with CSVD) develop stage 5 seizures in the amygdala kindling model (TLE) faster than age-matched control rats without CSVD. At odds, no differences between old SHRs and age-matched controls was observed in the development of PTZ kindling. Enalapril pre-treatment prevented the development of CSVD and normalized kindling development to control levels in SHRs. No difference was observed in the response to pharmacological treatment with carbamazepine or losartan. Overall, our study suggests that uncontrolled hypertension leading to CSVD might represent a risk factor for TLE. Further experimental studies are needed to unravel other risk factors that, along with CSVD, may predispose to TLE.