Mapping of Cerebral Blood Flow Changes during Audiogenic Seizures in Wistar Rats: Effect of Kindling

Abstract

Summary: The quantitative autoradiographic [14C]iodoantipyrine technique was applied to the measurement of rates of local cerebral blood flow (LCBF) during audio genic seizures in Wi star AS rats belonging to a genetic strain selected at the Centre de Neurochimie (Strasbourg, France) for their sensitivity to sound. Seizures were elic ited in naive rats never exposed to sound (single audio genic seizures) or in rats previously exposed to l�O seizure-inducing sound stimulations until generalization of the seizure to forebrain areas (referred to as "kindled animals"). During single audiogenic seizures, rates of LCBF increased over control values in all areas but the genu of the corpus callosum. The highest increases in LCBF (180-388%) were recorded in the inferior and su perior colliculus, reticular formation, monoaminergic cell groupings, especially the substantia nigra, posterior veg etative nuclei, and many thalamic and hypothalamic re gions. The lowest increases were seen in forebrain limbic regions and cortical areas. In kindled animals, LCBF rates increased over control levels in 67 areas of the 75In the breeding colony of our laboratory (Centre de Neurochimie, Strasbourg, France), we have se lected a strain of Wistar rats susceptible to audio genic seizures (Wistar AS) (Marescaux et aI., 1987). In these rats, the exposure to an intense sound stim ulus induces an epileptic seizure characterized by one or two wild running episodes lasting for about 10-30 s, followed by a tonic phase with dorsal hy perextension, the forelimbs stretched out forward and the hindlimbs flexed. This seizure is followed 9studied. LCBF increases were generally of a lower am plitude in kindled than in naive rats. Differences between the two groups of seizing rats were located mostly in brain-stem regions, mainly the inferior colliculus, reticu lar formation, substantia nigra, and posterior vegetative nuclei. Conversely, rates of LCBF were similar in fore brain areas of naive and kindled animals. In conclusion, the present data show that there is a good correlation between the structures known to be involved in the ex pression of audiogenic seizures (inferior col\iculus, retic ular formation, substantia nigra mainly) and the large in crease in LCBF during single audiogenic seizures, while rates of LCBF increase to a lesser extent in forebrain areas not involved in this type of seizures. The circula tory adaptation to kindled seizures is rather a decreased response in brain-stem regions and no change in the fore brain, although the kindling process induces a generaliza tion of the seizure from brain-stem to anterior regions.

The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years

“…This problem is very important both for practical goals [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86] and for theoretical issues, as well [68,76,77]. The examples of such effects are numerous, but in spite of this, the respective mechanisms stay mainly unexplored.…”

“…Thus, the good correlation between the blood supply levels in structures involved in the AS was demonstrated. The circulatory changes in kindled rats consisted in a decrease of blood flow, this fact reflecting the differences in the mechanisms of brain stem AS and audiogenic kindling [69].…”

“…In other audiogenic seizure-prone rats, the blood flow changes during audiogenic kindling was investigated (in WAS rats) (Centre de Neurochimie (Strasbourg, France)) [69]. The quantitative autoradiographic [ 14 C]-iodoantipyrine technique was applied to measure rates of local cerebral blood flow (LCBF) during audiogenic seizures.…”

Effect of stage 2 kindling on local cerebral blood flow rates in rats with genetic absence epilepsy

“…The measurement of local cerebral blood flow (LCBF) is frequently used to locate the areas involved in brain activation induced by epileptic seizures (Nehlig et al, 1995; Pereira de Vasconcelos et al, 1995, 2002;André et al, 2002; Chassagnon et al, 2005, 2006). The quantitative autoradiographic method using the freely diffusible tracer, [ 14 C]‐iodoantipyrine ([ 14 C]IAP), allows the measurement of rates of LCBF over very short periods ranging from 30–60 s and is specifically adapted to the measurement of functional changes occurring during short events such as seizures.…”

Audiogenic Seizures - Biological Phenomenon and Experimental Model of Human Epilepsies

“…Thus the good correlation between the involvement of structures in the AE progress and the increase of blood flow in them was discovered. The circulatory changes in kindled rats consisted in the decrease of blood flow, this fact reflecting the differences in respective mechanisms of brain stem AE seizures and audiogenic kindling (Nehlig et al, 1995). In KM rats the inhibitor of NO-synthase (L-NNA) increased the severity of seizures, mortality rate and intracranial hemorrhages.…”