Neurochemical profiles in cerebrospinal fluid of stroke-prone spontaneously hypertensive rats

Togashi, Hiroko; Matsumoto, Machiko; Yoshioka, Mitsuhiro; Hirokami, Mitsugu; Minami, Masaru; Saito, Hideya

doi:10.1016/0304-3940(94)90854-0

Cited by 68 publications

(36 citation statements)

References 13 publications

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“…It has been suggested that the extracellular Ch might not be a good index for cholinergic activity, since Ch levels do not correlate to the changes in extracellular ACh levels (43). However, we previously reported that the central cholinergic dysfunction observed in the vascular dementia animal models was accompanied with a decrease in CSF Ch as well as ACh (9,10,25,40). The present results also indicate that AF102B produced an increase in CSF Ch as well as ACh.…”

Section: Discussioncontrasting

confidence: 46%

“…We have reported that AF102B exerts an ameliorating effect on the impair ment of the passive avoidance response (39) in stroke prone spontaneously hypertensive rats, which showed a marked decrease in the CSF ACh level (25,40). We also observed that AF102B restored the ACh level in CSF dialysates of this vascular dementia animal model (H. Togashi, unpublished data).…”

Section: Discussionmentioning

confidence: 61%

“…CSF levels of the ACh have rarely been studied because of low concentrations due to the extremely rapid hydrolysis to choline (Ch). Recently, we have reported that central choli nergic function can be evaluated by measuring the CSF levels of ACh in anesthetized rats (9,10,25).…”

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confidence: 99%

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Acetylcholine Measurement of Cerebrospinal Fluid by In Vivo Microdialysis in Freely Moving Rats

Togashi

Matsumoto

Yoshioka

et al. 1994

Japanese Journal of Pharmacology

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Acetylcholine (ACh) and choline (Ch) levels in rat cerebrospinal fluid (CSF) were determined by in vivo microdialysis (CSF microdialysis) in both halothane-anesthetized and freely-moving rats. The Ch/ACh ratio in CSF perfused with Ringer's solution (30 ail/30 min) containing 10-5 M physostigmine, a centrally active cholinesterase inhibitor, was significantly lower than that in unprocessed CSF due to significantly higher ACh levels in the former. The successive measurement on the 2nd and 7th day after the guide cannula implantation demonstrated the feasibility of the CSF microdialysis method for repetitive monitoring of CSF ACh and Ch levels in freely moving rats without extensive tissue damage. Intra peritoneal administration of physostigmine caused an increase in CSF ACh levels, whereas administra tion of neostigmine, which cannot penetrate into the blood brain barrier, did not. Furthermore, a centrally active acetylcholinergic M,-receptor agonist, AF102B, produced an increase in CSF ACh and Ch levels. Thus, the present study demonstrates that CSF microdialysis is a useful method for evaluating overall cen tral cholinergic activity and investigating the pharmacological effects of various drugs that act via the central cholinergic system.

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Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 61%

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Acetylcholine Measurement of Cerebrospinal Fluid by In Vivo Microdialysis in Freely Moving Rats

Togashi

Matsumoto

Yoshioka

et al. 1994

Japanese Journal of Pharmacology

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“…Fourth, rats with multiple small embolizations have been shown to produce multiple infarctions and exhibit decreases in cholinergic markers [19] . Finally, there is a significant reduction in cholinergic markers, including ACh, in the neocortex, hippocampus and cerebrospinal fluid (CSF) in the spontaneously hypertensive stroke prone rat (SHspR), which is the best model for essential hypertension and stroke [20,21] . It has been suggested that patients with VaD also exhibit cholinergic deficits (reviewed in ref [22] ).…”

Section: Cholinergic Deficiency In Vad Animal Models and Vad Patientsmentioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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“…These behavioral symptoms were ameliorated by the psychostimulant methylphenidate, a firstchoice drug for the treatment of ADHD. Central cholinergic dysfunction and concomitant cognitive dysfunction have been noted in SHRSP (Kang et al, 1990;Togashi et al, 1994Togashi et al, , 1996Minami et al, 1997;Nakamura and Shirane, 1999;Shirane and Nakamura, 2000). Moreover, the dysfunction of nicotinic systems, such as decreases in high-affinity (i.e., ␣4␤2 sensitivity to [ 3 H]nicotine) and low-affinity (i.e., ␣7 sensitivity to 125 I-␣-bungarotoxin) nAChR binding sites, was also found in the brain regions of SHRSP (Yamada et al, 1987;Ferrari et al, 1999).…”

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α4β2 Nicotinic Acetylcholine Receptor Activation Ameliorates Impairment of Spontaneous Alternation Behavior in Stroke-Prone Spontaneously Hypertensive Rats, an Animal Model of Attention Deficit Hyperactivity Disorder

Ueno

Togashi²,

Matsumoto³

et al. 2002

J Pharmacol Exp Ther

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The objective of the present study was to elucidate the role of nicotine in impairment of spontaneous alternation behavior of juvenile stroke-prone spontaneously hypertensive rats (SHRSP), an animal model of attention deficit hyperactivity disorder (ADHD). Spontaneous alternation behavior assessed by a Y-maze task was significantly lower, and total arm entries were significantly higher in SHRSP than in genetic control Wistar-Kyoto rats. Nicotine (0.1-1 mg/kg, s.c.) dose dependently improved the spontaneous alternation deficit without affecting total arm entries in SHRSP. Nicotine-induced (1 mg/kg, s.c.) improvement was significantly abolished by the centrally acting nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (1 mg/kg, i.p.), but not by peripherally acting hexamethonium (5 mg/kg, i.p.), suggesting that nicotine-induced improvement is mediated via central nAChR. The ␣4␤2 nAChR antagonist dihydro-␤-erythroidine (3-10 mg/kg, i.p.) dose dependently counteracted nicotine-induced improvement of spontaneous alternation in SHRSP, whereas the ␣7 nAChR antagonist methyllycaconitine (3-10 mg/kg, i.p.) did not. In addition, the ␣4␤2 nAChR agonist RJR-2403 (N-methyl-4-(3-pyridinyl)-3-butene-1-amine; 1-10 mg/kg, s.c.) dose dependently and significantly improved the spontaneous alternation deficit. These findings revealed that nicotine improved spontaneous alternation behavior in SHRSP via the activation of ␣4␤2, but not ␣7, nAChR. Thus, the ␣4␤2 nAChR mechanism might be responsible for the spontaneous alternation deficit in juvenile SHRSP, an animal model of ADHD. This evidence indicates the possibility that selective ␣4␤2 nAChR agonists might be useful for treating attentional dysfunction in ADHD.

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Neurochemical profiles in cerebrospinal fluid of stroke-prone spontaneously hypertensive rats

Cited by 68 publications

References 13 publications

Acetylcholine Measurement of Cerebrospinal Fluid by In Vivo Microdialysis in Freely Moving Rats

Acetylcholine Measurement of Cerebrospinal Fluid by In Vivo Microdialysis in Freely Moving Rats

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

α4β2 Nicotinic Acetylcholine Receptor Activation Ameliorates Impairment of Spontaneous Alternation Behavior in Stroke-Prone Spontaneously Hypertensive Rats, an Animal Model of Attention Deficit Hyperactivity Disorder

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