Sima Mraovitch

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. These data suggest that insulin, via its specific receptors, may exert its central actions by affecting glucose utilization.

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. The specific epileptogenic sites identified within the thalamus may provide a new experimental model which should prove useful for exploring the thalamic and thalamo-cortical mechanisms underlying limbic and generalized convulsive seizure disorders.

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. Thus, it appears that the activation of CM-Pf neurons or fibers passing through it could play an important role in regulating primary cerebral vasodilation.

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. During CM-Pf stimulation, rCBF increased significantly (P less than 0.05, analysis of variance and Scheffes test) in all cerebral regions bilaterally ranging from +118% in parietal cortex to +38% in cerebellum. Although cerebral vasodilation elicited by CM-Pf stimulation persisted after unilateral transection of the cervical sympathetic trunk, the cortical CBF was significantly reduced (P less than 0.05) on the denervated side. Acute adrenalectomy significantly (P less than 0.05) decreased elevated rCBF during CM-Pf stimulation in all cortical regions (frontal-36%, parietal -34%, and occipital -27%) and in caudate nucleus (-37%). Thus, excitation of neurons originating in, or fibers passing through the CM-Pf can elicit a powerful cerebral vasodilation. The cerebral vasodilation is modulated by cervical sympathectomy and circulating adrenal hormones. We conclude that CM-Pf elicited vasodilation is at least partly mediated by intrinsic neural pathways.

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. The decrease in lCBF was not associated with significant changes in glucose metabolism. Thus, lesions of dopaminergic afferents to the caudate-putamen appear to provoke a sustained decrease in basal blood flow with unchanged local metabolic activity.

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

Abstract1. 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.2. On the basis of the c-fos regional expression and well-known efferent and afferent pathways linking these regions, a neuronal network relating the limbic, thalamo–striatal–cortical, and central autonomic systems, was constructed.3. The pattern of Fos immunoreactivity associated with long-lasting isocortical vasodilatation elicited by generalized convulsive seizures in anesthetized rat following cholinergic stimulation of the thalamus can be attributed to both the electrocortical activity and the long-lasting increase in cortical blood flow. We propose that the sustained cerebral cortical blood flow response during convulsive epileptic seizures may implicate intracerebral vasodilatory and vasoconstrictory neural mechanisms. Double-labeled NADPH-d and Fos-positive neurons implicated in maintaining the sustained isocortical vasodilatory response were found in the anterior lateral hypothalamic area. Inhibition of these neurons prevented the increase in cortical blood flow despite an increased metabolic demand manifested by the ictal electrocortical activity.4. Medial temporal lobe atrophy, including hippocampus, amygdala, and parahippocampal gyrus (piriform and entorhinal cortices) are the most common pathology in man. However the origin of medial lobe atrophy remain uncertain. Our results provide evidence that the allocortical microvascular inflammation may be in origin of the neurovascular degenerative processes leading to atrophy.

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.

FOS Induction in Brain Associated with Seizure and Sustained Cortical Vasodilation in Anesthetized Rat

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