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

Abstract

SUMMARYPurpose: Genetic absence epilepsy rats from Strasbourg (GAERS) are resistant to the progression of kindling seizures. We studied local cerebral blood flow (LCBF) changes in brain regions involved in seizures in both GAERS and nonepileptic rats (NEC) to map the differences that may be related to the resistance to kindling. Methods: Electrodes were implanted in the amygdala of adult NEC and GAERS male rats, which were stimulated to reach stage 2. Quantitative autoradiographic measurements of LCBF were performed by the [ 14 C]-iodoantipyrine ([14 C]IAP) autoradiographic technique allowing the precise mapping of regional perfusion changes. LCBF rates were measured bilaterally in 43 brain regions. The tracer infusion lasted for 60 s and started at 15 s before seizure induction. Results: Rates of LCBF increased in stimulated GAERS and NEC groups compared to nonstimulated controls. The LCBF increase in stimulated GAERS was larger and more widespread than that observed in stimulated NEC. The LCBF increase in the somatosensory cortex, ventrobasal and anterior thalamic nuclei, hypothalamus, subthalamic nucleus, piriform, entorhinal and perirhinal cortex, amygdala, CA2 region of hippocampus, and substantia nigra was statistically significantly larger in stimulated GAERS compared to stimulated NEC rats. Conclusion: The results show that more brain regions are activated by kindling stimulation in GAERS. This widespread activation in GAERS involves the somatosensory cortex and thalamus, which are both known to be involved in the expression of absence seizures as well as numerous limbic regions thought not to play a role in the expression of absence seizures, suggesting an interaction between corticothalamocortical and limbic circuitries.

Brain uptake of diazepam and phenytoin in a genetic animal model of absence epilepsy

“…This is consistent with the fact that diazepam is often used as a marker of cerebral blood flow 16 and that this parameter increases following convulsive seizures 15 . Interestingly, the brain uptake of diazepam was not enhanced in the mouse model of absence epilepsy, which may be attributed, in part, to the fact that cerebral blood flow does not increase in absence epilepsy but, rather, decreases 17,18 …”

Thalamic nuclei activity in idiopathic generalized epilepsy

“…From the 40 calculated HRFs, 6 were rejected for non-HRF-shape concordance. This finding demonstrates in humans involvement of intralaminar and anterior thalamic nuclei during GSWDs, suggesting that the corticoreticular 1,2,11 and the limbic systems 3,4 are implicated in the epileptic network. Ten of 67 peaks (5 positive, 5 negative) had a signal to noise ratio inferior to 2.…”

“…Recent studies demonstrated that changes (metabolic, hemodynamic, and kindling properties) 3,4 occur in the limbic structures involving the anterior thalamic nucleus (AN) during GSWDs, although no GSWDs are recorded in the AN. Many studies attempted to explore the circuits involved in the generation and propagation of GSWDs in IGE.…”

The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy

“…We have previously shown that 6 kindling stimulations in NECs and GAERS lead to stage 2 seizures (before the development of further kindling stages in NEC and the occurrence of the kindling resistance in GAERS). 26 Thus the experiment was designed to keep all NECs and GAERS at the same seizure stage for them to be comparable at the end of the kindling course for subsequent TH and PRV immunohistochemistry. These rats that received 6 kindling stimulations are referred here as GAERS-STIM and NEC-STIM.…”