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.

Limbic and/or generalized convulsive seizures elicited by specific sites in the thalamus.

Convulsive seizures were elicited by a single unilateral microinjection of the cholinergic muscarinic agonist, carbachol, into the thalamus. Moreover, using systematic single microinjections of carbachol, we identified specific regions within the thalamus which were the origin of behavioural and electrocortical correlates associated with limbic and/or generalized convulsive seizures. Neither serotonin, noradrenaline nor glutamate had any convulsive effect when injected into the epileptogenic thalamic areas.

Cerebrovascular and metabolic uncoupling in the caudate-putamen following unilateral lesion of the mesencephalic dopaminergic neurons in the rat.

Changes in local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) were assessed in dopaminergic primary target areas in the rat 6 weeks after unilateral lesion of dopaminergic neurons within the substantia nigra pars compacta (SNc) and adjacent ventrotegmental area (VTA) using 6-hydroxydopamine (6-OHDA). lCBF and lCGU were determined using the autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose method. Dopaminergic deafferentation provoked a marked unilateral lCBF decrease in the dorso-lateral portion of the rostral caudate-putamen.

Noncholinergic, nonadrenergic cortical vasodilatation elicited by thalamic centromedian-parafascicular complex.

The centromedian-parafascicular complex (CMPf) of the intralaminar thalamus was stimulated in anesthetized, ventilated rats, and cerebral cortical perfusion was continuously measured using laser Doppler flowmetry. Stimulation led to a frequency- and intensity-dependent increase in cortical perfusion (vasodilatation). The maximum response was seen at a rate of 200/s, and studied at 150 microA, was a 120 +/- 27% (n = 6) increase in flow.

Differential cerebrovascular and metabolic responses in specific neural systems elicited from the centromedian-parafascicular complex.

The effect of electrical stimulation of the centromedian-parafascicular complex on local cerebral blood flow and local cerebral glucose utilization was investigated in anesthetized, paralysed and ventilated rats. Local cerebral blood flow and local cerebral glucose utilization were measured in separate groups of animals using the autoradiographic (14C)iodoantipyrine and (14C)2-deoxyglucose methods, respectively. Because of the well-established centromedian-parafascicular complex neuroanatomical connections, three functional neuronal systems were analysed and compared: the extrapyramidal motor system the limbic system and the reticular formation, also known as the ascending activating system.

Subcortical cerebral blood flow and metabolic changes elicited by cortical spreading depression in rat.

Changes in cerebral cortical perfusion (CBFLDF), local cerebral blood flow (lCBF) and local cerebral glucose utilization (lCGU) elicited by unilateral cortical spreading depression (SD) were monitored and measured in separate groups of rats anesthetized with alpha-chloralose. CBFLDF was recorded with laser Doppler flowmetry, while lCBF and lCGU were measured by the quantitative autoradiographic [14C]iodoantipyrine and [14C]-2-deoxyglucose methods, respectively. SD elicited a wave of hyperemia after a latency of 2 to 3 min followed by an oligemic phase.

Metabolic anatomy of the focal epilepsy produced by cessation of chronic intracortical GABA infusion in the rat.

Cessation of chronic (5 days), unilateral infusion of GABA into the somatomotor cortex of rats induces focal epileptic spikes which remain limited to the infused site and never evolve into generalized seizures. We have considered this finding as a new model of focal epilepsy and named it "GABA withdrawal syndrome". In the present study, we have measured local cerebral glucose utilization in order to map the cortical and subcortical regions involved in the GABA withdrawal syndrome.

Effects of hyperinsulinemia on local cerebral insulin binding and glucose utilization in normoglycemic awake rats.

The present study was carried out to characterize the effects of insulin, using the euglycemic hyperinsulinemic clamp, on insulin binding and glucose utilization in specific areas of rat brain, by autoradiographic methods. Binding of [125I]Insulin was significantly higher in the hippocampus CA1, the ventromedial and lateral hypothalamus nuclei of the hyperinsulinemic rats than in control rats. Glucose utilization was slightly but not significantly decreased in the hippocampus CA1, the ventromedial and lateral hypothalamus of hyperinsulinemic rats.

Effect of stimulation of the sphenopalatine ganglion on cortical blood flow in the rat.

The effects of electrical stimulation of the sphenopalatine ganglion on cortical blood flow and gas partial pressures (PO2 and PCO2) were studied in the anesthetized rat. Tissue PO2, PCO2, and local CBF were measured simultaneously in both parietal cortices by means of mass spectrometry. Stimulation of the sphenopalatine ganglion increased CBF and tissue PO2 by approximately 50 and 20%, respectively, in the ipsilateral parietal cortex.

Metabolism-independent cerebral vasodilation elicited by electrical stimulation of the centromedian-parafascicular complex in rat.

Changes in local cerebral blood flow (1CBF) and local cerebral glucose utilization (1CGU) during electrical stimulation of the centromedian-parafascicular complex in rat have been determined using the autoradiographic [14C]iodoantipyrine and 2-deoxy-[14C]glucose methods. In 40 out of 47 cerebral regions measured, the centromedian-parafascicular complex (CM-Pf) stimulation elicited an increase in 1CBF. The increase in 1CBF was not associated with a rise in cerebral metabolism in 38 regions.

A role of insular cortex in cardiovascular function.

We sought to determine whether the insular cortex contributes to the regulation of arterial blood pressure (AP). Responses to electrical and chemical stimulation of the cortex were studied in the anesthetized, paralyzed, and artificially ventilated Sprague-Dawley rat. The insular cortex was initially defined, anatomically, by the distributions of retrogradely labeled perikarya following injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the nucleus tractus solitarii (NTS).

Cerebrovascular changes elicited by electrical stimulation of the centromedian-parafascicular complex in rat.

Electrical stimulation of the centromedian-parafascicular complex (CM-Pf) in anesthetized (chloralose) and paralyzed (tubocurarine) rats elicits a widespread cerebrovascular dilatation. Regional cerebral blood flow (rCBF) was measured in dissected tissue samples of 10 brain regions (medulla, pons, cerebellum, inferior colliculus, superior colliculus, frontal parietal and occipital cortices, caudate-putamen and corpus callosum) by [14C]iodoantipyrine method. In unstimulated and sham-operated rats rCBF ranged from 40 +/- 3 (ml/100 g/min) in corpus callosum to 86 +/- 6 (ml/100 g/min) in inferior colliculus.

Two neural mechanisms in rat fastigial nucleus regulating systemic and cerebral circulation.

We have studied in anesthetized (alpha-chloralose) and paralyzed (d tubocurarine) rats the effects of electrical stimulation of the fastigial nucleus (FN) on local cerebral blood flow (lCBF) and its relationship to intracerebral PO2, and PCO2 and to the systemic arterial pressure (Pa). Mass spectrometry was used to measure quantitatively lCBF (repetitively) and cerebral PO2 and PCO2 (continuously). A systematic exploration of the FN for an increase in Pa and/or lCBF revealed that the most active sites for the rise in Pa were localized within the rostral FN, while those that elicited an increase in lCBF were found throughout the rostrocaudal extent of the FN.

Widespread reductions in cerebral blood flow and metabolism elicited by electrical stimulation of the parabrachial nucleus in rat.

We have studied the effect of electrical stimulation of the parabrachial nucleus (PBN) and adjacent areas of dorsal pons on regional cerebral blood flow (rCBF) and glucose utilization (rCGU) in anesthetized (chloralose), paralyzed (tubocurarine) rats. rCBF and rCGU were measured in dissected tissue samples of 9 brain regions by the [14C]iodoantipyrine and [14C]2-deoxyglucose method, respectively. Electrical stimulation restricted to the medial parabrachial nucleus (PBNm, n = 5) elicited significant (P less than 0.

Lesions of the basal forebrain in rat selectively impair the cortical vasodilation elicited from cerebellar fastigial nucleus.

We sought to determine in rat, whether interruption of the major extrathalamic projections to the cerebral cortex originating in and projecting through the basal forebrain (BF), will impair the increase in regional cerebral blood flow (rCBF), but not metabolism, elicited in the cerebral cortex by electrical stimulation of the cerebellar fastigial nucleus (FN). Studies were conducted in anesthetized, paralyzed, ventilated rats, with blood gases controlled and AP maintained in the autoregulated range. Electrolytic lesions were placed unilaterally in the BF at the level of the lateral preoptic region lying in rostral portions of the medial forebrain bundle and resulted in a reduction of up to 47% of the choline acetyltransferase activity in the ipsilateral cerebral cortex.

Global increase in cerebral metabolism and blood flow produced by focal electrical stimulation of dorsal medullary reticular formation in rat.

We sought to determine whether the increases in local cerebral blood flow (LCBF) elicited by focal electrical stimulation within the dorsal medullary reticular formation (DMRF), are secondary to or independent of, increased local cerebral glucose utilization (LCGU). Rats were anesthetized (chloralose), paralyzed, artificially ventilated and arterial pressure and blood gases controlled. LCBF and LCGU were determined in two separate groups of animals, using the autoradiographic [14C]iodoantipyrine and [14C]2-deoxyglucose methods, respectively.

Role of the nucleus parabrachialis in cardiovascular regulation in cat.

Electrical stimulation of the nucleus parabrachialis (NPB) and surrounding areas of the dorsolateral pons in anesthetized immobilized cats elicits a rise of arterial pressure (AP) and tachycardia: the parabrachial pressor response (PBPR). The most excitable sites were concentrated within the intermediate one-third of the NPB in its medial and lateral subdivisions. The magnitude of pressor responses and their stimulus sensitivity were substantially greater in NPB than in adjacent areas of the dorsal pons including nucleus locus coeruleus and brachium conjunctivum, suggesting that cardiovascular responses heretofore attributed to locus coeruleus may have been due to excitation of the NPB.