The Cerebrovascular Effects of Physostigmine Are Not Mediated through the Substantia Innominata

Peruzzi, P; Lacombe, Pierre; Moro, Véronique; Vaucher, Elvire; Levy, F.; Seylaz, Jacques

doi:10.1006/exnr.1993.1131

Cited by 16 publications

(12 citation statements)

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“…Because cholinesterase inhibitors strongly increase ce‐rebral blood flow, cerebrovascular investigations were conducted in an experimental model of cholinergic deficit. These experiments failed to confirm that cholinesterase inhibitors can enhance the functioning of the basalocortical system 1–3. Thus, no evi‐dence has been provided for NBM lesion‐related cerebrovascular changes in the ef‐fects of indirect cholinergic agonists.…”

Section: Introductionmentioning

confidence: 99%

“…The present study was designed to determine if the cerebrovascular responses to physostigmine and tacrine were altered 3–5 weeks after lesioning of the NBM, there‐by testing whether denervation supersensitivity alters the functioning of the basalo‐cortical system. The results were compared with those previously obtained 1–2 weeks post‐lesion 2,3. Cerebral blood flow (CBF) was measured in various brain re‐gions during i.v.…”

Section: Introductionmentioning

confidence: 99%

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Differentiated Cerebrovascular Effects of Physostigmine and Tacrine in Cortical Areas Deafferented from the Nucleus Basalis Magnocellularis Suggest Involvement of Basalocortical Projections to Microvessels

Peruzzi

Euw

Lacombe

2000

Annals of the New York Academy of Sciences

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Cholinesterase inhibitors used to treat Alzheimer's disease according to the principle of cholinergic replacement therapy have proved to be less beneficial than expected. The present study was designed to investigate the cerebrovascular response to physostigmine and tacrine in the experimental model of lesioning of the nucleus basalis magnocellularis (NBM), a model involving a cholinergic deficit. Regional cerebral blood flow was measured by the [14C]iodoantipyrine tissue sampling technique in conscious rats infused with i.v. physostigmine (0.2 mg/kg/h), tacrine (8 mg/kg/h), or saline, 3-5 weeks after unilateral lesion of the NBM with ibotenic acid. Physostigmine and tacrine dose-dependently increased blood flow in most cortical and subcortical regions compared to the control group. However, physostigmine caused smaller blood flow increases in several areas, mostly cortical, of the lesioned compared to the intact hemisphere. The converse was observed with tacrine. A facilitated circulatory response appeared in cortical areas deafferented from the NBM, especially in the frontal cortex. These results provide evidence for distinct NBM-dependent components of the cortical cerebrovascular effects of physostigmine and tacrine. They suggest the involvement of different cellular postsynaptic targets of the NBM. The physostigmine-type effects could involve direct projects onto an inhibitory cortical interneuron supersensitized by deafferentation. This arrangement may explain why physostigmine and perhaps other cholinergic agonists are unable to specifically compensate for a deficit in NBM functioning. The tacrine-type effects presumably involve projections to the microvasculature, including perivascular astrocytes. The neurovascular junction would be sensitized by deafferentation from the NBM. Our data suggest that the regulatory mechanisms of blood flow originating in the NBM might constitute a target of neurodegenerative processes of Alzheimer's disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differentiated Cerebrovascular Effects of Physostigmine and Tacrine in Cortical Areas Deafferented from the Nucleus Basalis Magnocellularis Suggest Involvement of Basalocortical Projections to Microvessels

Peruzzi

Euw

Lacombe

2000

Annals of the New York Academy of Sciences

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“…These data show that NBM neurons are capable of exerting a neurogenic control of the cortical circulation, and that this control is age‐dependent. The frontal predominance exhibited by the uncoupled cortical responses coincides, first, with that of the changes in ChAT activity after NBM lesion, 2 and second, with that of the cholinergic NBM projections which impinge on cortical microvessels 5 . Furthermore, it has been shown by Vaucher and Hamel 5 that most of these connections between the nerve and vessels concern the microvasculature and involve perivascular astrocyte endfeet, the latter being endowed with muscarinic receptors 6 …”

Section: Resultsmentioning

confidence: 84%

“…In earlier studies we showed that electrical stimulation of the rat nucleus basalis of Meynert (NBM) induces large increases in cerebral blood flow, particularly in frontal cortical areas, mediated by cholinergic mechanisms 1 . Conversely, a lesion in the NBM induced modest but significant cortical blood flow reduction 2 . These data indicate that the cholinergic projections from the basal forebrain can considerably influence the cortical circulation, and exert a moderate tonic influence in resting conditions.…”

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confidence: 82%

Reduced Cortical Vasodilatory Response to Stimulation of the Nucleus Basalis of Meynert in the Aged Rat and Evidence for a Control of the Cerebral Circulation

Lacombe

Sercombe

Vaucher

et al. 1997

Annals of the New York Academy of Sciences

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In earlier studies we showed that electrical stimulation of the rat nucleus basalis of Meynert (NBM) induces large increases in cerebral blood flow, mainly through cholinergic mechanisms. We then investigated the effect of aging on this influence by measuring cortical blood flow (CoBF) and tissue gas partial pressures (PtO2, PtCO2) in the conscious young adult and aged rat. NBM stimulation increased frontal (+101%) and parietal (+29%) CoBF in young rats. The effects were halved in aged rats. Moreover, PtO2 was significantly increased in young but not in aged rats. By contrast, the corticovascular reactivity to hypercapnia did not differ between young and aged rats, nor did the potentiating vasodilator effect of physostigmine. In combined autoradiographic measurements of cerebral blood flow and cerebral glucose utilization, we recently found that the cortical circulatory response to NBM stimulation was not accompanied by significant metabolic change. Thus, the blood flow changes observed in the cortex cannot be ascribed to increased metabolic activity. The distribution of this uncoupling coincides with that of cholinergic NBM projections directly impinging on cortical microvessels. These data support the cortical microcirculation and suggest the possible involvement of NBM dysfunction in the pathology of cortical microcirculation.

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“…Indeed, the direct stimulation of the substantia innominata or the nucleus basalis of Meynert elicits an increased cortical CBF that is not associated to a parallel change in CMR glc (Vaucher et al 1997) being hypothesized to be implicated in the brain parenchyma during NA, suggesting that AchE modulates glial activation and CBF. In addition, nucleus basalis of Meynert lesion studies in animal-models demonstrated to decrease cortical CBF (Peruzzi et al 1993). In contrast, it has been shown that lesions of the nucleus basalis of Meynert do result in an unexpected preservation of CMR glc associated to an increase in the density of GLUT3 (glucose transporter 3) glucose transporters in the cortex (Simpson et al 1994).…”

Section: Physiological Background As Related To Dementiamentioning

confidence: 99%

Strategies for molecular imaging dementia and neurodegenerative diseases

Schaller¹

2008

NDT

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Dementia represents a heterogeneous term that has evolved to describe the behavioral syndromes associated with a variety of clinical and neuropathological changes during continuing degenerative disease of the brain. As such, there lacks a clear consensus regarding the neuropsychological and other constituent characteristics associated with various cerebrovascular changes in this disease process. But increasing this knowledge has given more insights into memory deterioration in patients suffering from Alzheimer's disease and other subtypes of dementia. The author reviews current knowledge of the physiological coupling between cerebral blood fl ow and metabolism in the light of state-of-the-art-imaging methods and its changes in dementia with special reference to Alzheimer's disease. Different imaging techniques are discussed with respect to their visualizing effect of biochemical, cellular, and/or structural changes in dementia. The pathophysiology of dementia in advanced age is becoming increasingly understood by revealing the underlying basis of neuropsychological changes with current imaging techniques, genetic and pathological features, which suggests that alterations of (neuro)vascular regulatory mechanisms may lead to brain dysfunction and disease. The current view is that cerebrovascular deregulation is seen as a contributor to cerebrovascular pathologies, such as stroke, but also to neurodegenerative conditions, such as Alzheimer's disease. The better understanding of these (patho)physiological mechanisms may open an approach to new interventional strategies in dementia to enhance neurovascular repair and to protect neurovascular coupling.

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The Cerebrovascular Effects of Physostigmine Are Not Mediated through the Substantia Innominata

Cited by 16 publications

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Differentiated Cerebrovascular Effects of Physostigmine and Tacrine in Cortical Areas Deafferented from the Nucleus Basalis Magnocellularis Suggest Involvement of Basalocortical Projections to Microvessels

Differentiated Cerebrovascular Effects of Physostigmine and Tacrine in Cortical Areas Deafferented from the Nucleus Basalis Magnocellularis Suggest Involvement of Basalocortical Projections to Microvessels

Reduced Cortical Vasodilatory Response to Stimulation of the Nucleus Basalis of Meynert in the Aged Rat and Evidence for a Control of the Cerebral Circulation

Strategies for molecular imaging dementia and neurodegenerative diseases

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