Aggravation of seizure-associated microvascular injuries by ibuprofen may involve multiple pathways.

Purpose: Recently we reported that intrathalamic microinjection of carbachol triggers generalized convulsive seizures (GCS) followed by severe inflammatory response including edema, microhemorrhages, and subsequent degeneration of amygdaloallocortical area. Our further observations of increased expression of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β immunoreactivity (IR) confirmed the inflammatory nature of the brain damage following GCS. In the presented experiments, we addressed possible effects of a nonspecific cyclooxygenase (COX) inhibitor (ibuprofen), in the development of inflammatory response following thalamic-induced GCS.

Post-seizures amygdaloallocortical microvascular lesion leading to atrophy and memory impairment.

Although the incidence of seizures after a cerebrovascular event including intracerebral hemorrhage has been widely recognized, the present studies have demonstrated that generalized convulsive seizures can cause multifocal amygdaloallocortical hemorrhage and tissue necrosis, the origin of which remains to be established. The seizure-elicited amygdaloallocortical injured area, which we refer to as a focal injury-prone area (FIPA), was caused by cholinergic stimulation of the ventroposterolateral and thalamic reticular nuclei. The amygdaloallocortical injury was preceded by focal absence of neuronal COX-2 and presence of microvascular immunoreactivity to the pro-inflammatory cytokines, IL-1beta and TNF-alpha.

Isocortical hyperemia and allocortical inflammation and atrophy following generalized convulsive seizures of thalamic origin in the rat.

1. Generalized convulsive seizures can be elicited by a single unilateral microinjection of the cholinergic muscarinic agonist, carbachol, into the specific sites of the thalamus including ventral posterolateral and the reticular thalamic nuclei. The implication of the thalamic specific and reticular neurons is reviewed and discussed.

Interactions between limbic, thalamo-striatal-cortical, and central autonomic pathways during epileptic seizure progression.

We used immunocytochemistry to determine the regional and temporal distribution of Fos protein expression in awake and unrestrained rats after a unilateral stereotaxic microinjection of a cholinergic agonist, carbachol, in the thalamic ventroposterolateral and reticular nuclei, previously shown to cause limbic and generalized convulsive seizures. The microinjection of carbachol elicits behavioral alterations including immobilization, staring, facial and jaw clonus, rearing, and falling, followed by recurrent generalized convulsive seizures, and a pattern of c-fos expression throughout the brain. In addition to the hypothalamic paraventricular and supraoptic nuclei, the initial induction of c-fos expression was observed as early as 15 minutes after the carbachol microinjection, in the piriform and entorhinal cortices, the thalamic paraventricular, the supramammilary, the lateral parabrachial nuclei, and the central gray.

FOS induction in brain associated with seizure and sustained cortical vasodilation in anesthetized rat.

Purpose: By estimating the anatomical distribution of neurons expressing c-fos protein, we sought to establish whether the intrinsic neural systems known to be implicated in the cerebrovascular regulation were activated during the increase in cortical blood flow associated with epileptic seizures.

Methods: A single unilateral microinjection of the cholinergic agonist, carbachol, in the thalamic generalized convulsive seizure area was used in anesthetized rats to elicit recurrent episodes of electrocortical epileptiform activity and an increase in cortical blood flow. Neuronal expression of Fos protein was analyzed to identify activated brain regions.