Eclampsia-Like Seizures and Electroencephalographic Changes in Pregnant Rabbits with Endothelin-1 Injections

Abstract

To examine the possible role of endothelin and vasospasm in eclamptic seizures, we studied and analyzed the electroencephalograms (EEG) of endothelin-1 (ET-l)-treated pregnant, nonpregnant and sham control (dextrose-treated) rabbits. After multiple intravenous bolus injections of ET-1 (500 pmol/kg) or 5% dextrose in the rabbits, we recorded EEG directly from the brain cortex and analyzed by Fast Fourier Transform (FFT). Water content was measured in the brain of all groups (n = 7). Repeated seizures occurred in all of the pregnant and 2 of the nonpregnant rabbits by variable doses of ET-1. FFT analysis showed remarkable changes in frequency and power arrays characterized by mild to severe form of dysrhythmia, high-voltage spikes, high-voltage fast and slow waves after ET-1 injections. Water content was increased in brain mass in ET-1-treated rabbits (p = 0.001) suggesting an ET-1-induced edema. Histologically we confirmed that ET-1 caused ischemic changes in brain tissues. However, ET-1 induced more pronounced changes in behavior, EEG, brain edema or ischemia in pregnant than in nonpregnant groups. The injections of exogenous ET-1 into the brain substances were strongly suggested by immunohistochemical study with polyclonal antiendothelin antibody in brain tissue sections. Therefore, we assume that endothelin along with other vasoactive substances causes acute cerebral vasospasm and ischemia inducing EEG changes leading to ultimate clinical convulsions in eclampsia.

Anticholinergics Induce Eclamptic Seizures

“…We demonstrated that the injection of endothelin-1 induced vasospasms and liver ischemia resulting in HELLP syndrome-like changes of blood parameters in female rabbits 14 and also demonstrated that the injection of endothelin-1 caused acute cerebral vasospasms and eclampsia-like seizures in pregnant rabbits. 15 Therefore, vasospasms of the vessels reflect hyperactivity of the sympathetic nervous system. [16][17][18][19][20] The effectiveness of long-term epidural anesthesia by bupivacaine in order to suppress the sympathetic hyperactivity in cases with eclampsia and preeclampsia was demonstrated.…”

Vasospasms Are Characteristic in Cases with Eclampsia/Preeclampsia and HELLP Syndrome: Proposal of an Angiospastic Syndrome of Pregnancy

“…We demonstrated that the injection of endothelin-1 induced vasospasms and liver ischemia resulting in HELLP syndrome-like changes of blood parameters in female rabbits 10 and also demonstrated that the injection of endothelin-1 caused acute cerebral vasospasms and eclampsia-like seizures in pregnant rabbits. 11 Vasospasms of the vessels reflect hyperactivity of the sympathetic nervous system. Schobel et al 12 reported that postganglionic sympathetic nerve activity of vascular smooth muscle was increased by means of intraneural microelectrodes in preeclamptic women.…”