Simultaneous investigation of the neuronal and vascular compartments in the guinea pig brain isolated in vitro

Curtis, Marco de; Biella, Gerardo; Buccellati, Carola; Folco, Giancarlo

doi:10.1016/s1385-299x(98)00044-0

Cited by 78 publications

(74 citation statements)

References 16 publications

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“…To reproduce our findings in a system closer to the in vivo situation, we further investigated the effect of CRP in the in vitro isolated guinea pig brain preparation, in which the complex interactions between the vascular and the neuronal compartments are preserved. 17,27,28 Using this model, functional alterations in BBB can be monitored by measuring changes in the extracellular potassium concentration…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Kuhlmann

Librizzi

Closhen³

et al. 2009

Stroke

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107

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Background and Purpose-Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood-brain barrier stability and to analyze the underlying signaling pathways. Methods-We used a cell coculture model of the blood-brain barrier and the guinea pig isolated whole brain preparation. Results-We could show that CRP at clinically relevant concentrations (10 to 20 g/mL) causes a disruption of the blood-brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fc␥ receptors CD16/32 followed by p38-mitogen-activated protein kinase-dependent reactive oxygen species formation by the NAD(P)H-oxidase. The resulting oxidative stress increased myosin light chain kinase activity leading to an activation of the contractile machinery. Blocking myosin light chain phosphorylation prevented the CRP-induced blood-brain barrier breakdown and the disruption of tight junctions. Conclusions-Our data identify a previously unrecognized mechanism linking CRP and brain edema formation and present a signaling pathway that offers new sites of therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Kuhlmann

Librizzi

Closhen³

et al. 2009

Stroke

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107

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“…), brains of adult Hartley guinea pigs (150 -250 g weight; Charles River, Comerio, Italy) were isolated and transferred to an incubation chamber, according to the previously described technique (Llinás et al, 1981;de Curtis et al, 1991de Curtis et al, , 1998Muhlethaler et al, 1993). A saline solution composed of the following (in mM): 126 NaCl, 3 KCl, 1.2 KH 2 PO 4 , 1.3 MgSO 4 , 2.4 CaCl 2 , 26 NaHCO 3 , 15 glucose, and 3% dextran, molecular weight 70.000, oxygenated with a 95% O 2 /5% CO 2 gas mixture, pH 7.3, was arterially perfused in vitro at 7 ml/min.…”

Section: Methodsmentioning

confidence: 99%

Hippocampus-Mediated Activation of Superficial and Deep Layer Neurons in the Medial Entorhinal Cortex of the Isolated Guinea Pig Brain

Gnatkovsky¹,

Curtis²

2006

J. Neurosci.

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The entorhinal cortex (EC) is regarded as the structure that regulates information flow to and from the hippocampus. It is commonly assumed that superficial and deep EC neurons project to and receive from the hippocampal formation, respectively. Anatomical evidences suggest that both the hippocampal output and deep EC neurons also project to superficial EC layers. To functionally characterize the interlaminar synaptic EC circuit entrained the by hippocampal output, we performed simultaneous intracellular recordings and laminar profile analysis in the medial EC (m-EC) of the in vitro isolated guinea pig brain after polysynaptic hippocampal activation by lateral olfactory tract (LOT) stimulation. Optical imaging of voltage-generated signals confirmed that the LOT-evoked hippocampusmediated response is restricted to the m-EC. The hippocampal output generated an extracellular current sink in layers V-VI, coupled with an EPSP in deep neurons. Deep neuron firing was terminated by a biphasic IPSP. The earliest response observed in superficial layer neurons was characterized by a feedforward IPSP of circa 100 ms (Ϫ69 Ϯ 1.3 mV reversal potential) abolished by local application of 1 mM bicuculline. The feedforward IPSP was followed by a delayed EPSP blocked by AP-5 (100 M), presumably mediated by deep-tosuperficial m-EC connections.Our findings demonstrate that superficial m-EC cells are inhibited by the hippocampal output via a feedforward pathway that prevents activity reverberation in the hippocampal-EC-hippocampal loop. We propose that such inhibition could serve as a protective mechanism to prevent epileptic hyperexcitability.

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“…The isolated whole brain preparation has been previously documented in detail (de Curtis et al, 1991(de Curtis et al, , 1998Muhlethaler et al, 1993) and will only briefly be described here. After barbiturate anesthesia (thiopentothal sodium, 20 mg / kg), young adult guinea pigs (150 -300 gm) were perf used through the heart with a cold (4 -10°C) carbogenated (95% O 2 and 5% CO 2 ) solution composed of (in mM): 126 NaC l, 3 KC l, 1.2 K H 2 PO 4 , 1.3 MgSO 4 , 2.4 CaCl 2 , 26 NaHC O 3 , 15 glucose, 2.1 H EPES, 0.4 thiourea, 0.5 ascorbic acid, and 3% dextran (molecular weight 70,000).…”

Section: Methodsmentioning

confidence: 99%

Evidence for Spatial Modules Mediated by Temporal Synchronization of Carbachol-Induced Gamma Rhythm in Medial Entorhinal Cortex

2000

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Fast (␥) oscillations in the cortex underlie the rapid temporal coordination of large-scale neuronal assemblies in the processing of sensory stimuli. Cortical ␥ rhythm is modulated in vivo by cholinergic innervation from the basal forebrain and can be generated in vitro after exogenous cholinergic stimulation. Using the isolated guinea pig brain, an in vitro preparation that allows for the study of an intact cerebrum, we studied the spatial features of ␥ activity evoked by the cholinomimetic carbachol (CCh) in the medial entorhinal cortex (mEC). ␥ activity induced by either arterial perfusion or intraparenchymal application of CCh showed a phase reversal across mEC layer II and was reduced or abolished in a spatially localized region by focal infusions of atropine, bicuculline, and CNQX. In addition, a spatially restricted zone of ␥ activity could be induced by passive diffusion of CCh from a recording pipette. Finally, ␥ oscillations recorded at multiple sites across the surface of the mEC using array electrodes during arterial perfusion of CCh demonstrated a decline in synchronization (coherence) as the interelectrode distance increased. This effect was independent of the signal amplitude and was specific for ␥ as opposed to theta-like activity induced by CCh in the same experiments.These results suggest that CCh-induced ␥ oscillations in the mEC are mediated through direct muscarinic excitation of a highly localized reciprocal inhibitory-excitatory network located in superficial layers. We propose that functional cortical modules of highly synchronous ␥ oscillations may organize incoming (cortical) and outgoing (hippocampal) information in the mEC.

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Simultaneous investigation of the neuronal and vascular compartments in the guinea pig brain isolated in vitro

Cited by 78 publications

References 16 publications

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption

Hippocampus-Mediated Activation of Superficial and Deep Layer Neurons in the Medial Entorhinal Cortex of the Isolated Guinea Pig Brain

Evidence for Spatial Modules Mediated by Temporal Synchronization of Carbachol-Induced Gamma Rhythm in Medial Entorhinal Cortex

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