Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally

Saad, Wilson Abrão; Guarda, Ismael Francisco Motta Siqueira; Camargo, Laa; Santos, Talmir Augusto Faria Brizola dos; Guarda, Renata Saad; Saad, Wael A.; Simões, Silvio Jorge Coelho; Rodrigues, J. Antunes

doi:10.1590/s0100-879x2003000700010

Cited by 14 publications

(6 citation statements)

References 29 publications

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“…Note that, the hippocampal formation and adjacent areas were dramatically hypoperfused, as demonstrated by lack of visible, FITC‐albumin filled vessels. Taken together, these results suggest that pilocarpine caused two different cerebrovascular changes, one consisting of increased BBB permeability and the other related to hemodynamic changes (Saad et al, 2003).…”

Section: Resultsmentioning

confidence: 81%

“…Non‐CNS effects of pilocarpine are observed at dosages much lower (1/20th) than those used to induce SE (Cook and Persinger, 1999). Very low dosages of peripherally administered pilocarpine (4 mg/kg) caused a substantial decrease in arterial pressure (Saad et al, 2003). Pilocarpine can also directly activate WBC, therefore decreasing the CD4/CD8 T‐lymphocyte ratio (Arzt et al, 1989; Prync et al, 1992).…”

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confidence: 99%

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In Vivo and In Vitro Effects of Pilocarpine: Relevance to Ictogenesis

Marchi¹,

Oby²,

Batra³

et al. 2007

Epilepsia

136

144

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Summary:Objectives: A common experimental model of status epilepticus (SE) utilizes intraperitoneal administration of the cholinergic agonist pilocarpine preceded by methylscopolamine treatment. Currently, activation of cholinergic neurons is recognized as the only factor triggering pilocarpine SE. However, cholinergic receptors are also widely distributed systemically and pretreatment with methyl-scopolamine may not be sufficient to counteract the effects of systemically injected pilocarpine. The extent of such peripheral events and the contribution to SE are unknown and the possibility that pilocarpine also induces SE by peripheral actions is yet untested.Methods: We measured in vivo at onset of SE: brain and blood pilocarpine levels, blood-brain barrier (BBB) permeability, Tlymphocyte activation and serum levels of IL-1β and TNF-α. The effects of pilocarpine on neuronal excitability was assessed in vitro on hippocampal slices or whole guinea pig brain preparations in presence of physiologic or elevated [K + ] out .Results: Pilocarpine blood and brain levels at SE were 1400 ± 200 µM and 200 ± 80 µM, respectively. In vivo, after pilocarpine injection, increased serum IL-1β, decreased CD4:CD8 T-lymphocyte ratios and focal BBB leakage were observed. In vitro, pilocarpine failed to exert significant synchronized epileptiform activity when applied at concentrations identical or higher to levels measured in vivo. Intense electrographic seizure-like events occurred only in the copresence of levels of K + (6 mM) mimicking BBB leakage.Conclusions: Early systemic events increasing BBB permeability may promote entry of cofactors (e. g. K + ) into the brain leading to pilocarpine-induced SE. Disturbance of brain homeostasis represents an etiological factor contributing to pilocarpine seizures.

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Section: Resultsmentioning

confidence: 81%

mentioning

confidence: 99%

In Vivo and In Vitro Effects of Pilocarpine: Relevance to Ictogenesis

Marchi¹,

Oby²,

Batra³

et al. 2007

Epilepsia

136

144

View full text Add to dashboard Cite

show abstract

“…In brain slices or isolated guinea pig brain, seizure‐like events could be evoked by pilocarpine only in the co‐presence of elevated K + concentrations, mimicking actions that occur when BBB permeability function is compromised (3,4). Based on the premises established from previous work and showing that pilocarpine can directly activate muscarinic receptors on brain microvasculature and white blood cells (5,6), Marchi and colleagues reported the following three interesting findings:…”

Section: Commentarymentioning

confidence: 97%

Pilocarpine-Induced Seizures Revisited: What Does the Model Mimic?

Vezzani¹

2009

Epilepsy Curr

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are etiologic cofactors in the pathogenesis of pilocarpine SE while acute osmotic disruption of the BBB is sufficient to elicit seizures.Whether an inflammatory-vascular-BBB mechanism could apply to the lithium-pilocarpine model is unknown. LiCl facilitated seizures induced by low-dose pilocarpine by activation of circulating T-lymphocytes and mononuclear cells. Serum IL-1β levels increased and BBB damage occurred concurrently to increased theta EEG activity. These events occurred prior to SE induced by cholinergic exposure. SE was elicited by lithium and pilocarpine irrespective of their sequence of administration supporting a common pathogenetic mechanism. Since IL-1β is an etiologic trigger for BBB breakdown and its serum elevation occurs before onset of SE early after LiCl and pilocarpine injections, we tested the hypothesis that intravenous administration of IL-1 receptor antagonists (IL-1ra) may prevent pilocarpine-induced seizures. Animals pre-treated with IL-1ra exhibited significant reduction of SE onset and of BBB damage. Our data support the concept of targeting systemic inflammation and BBB for the prevention of status epilepticus.COMMENTARY E xperimental models of seizures and epilepsy have been invaluable for understanding of the basic mechanisms underlying ictogenesis and epileptogenesis as well as for developing new therapeutic options. It is, therefore, of utmost importance to know the pathophysiological basis of the experimental model and which human pathological situations it mimics.One of the earliest and most frequently used models for evoking experimental status epilepticus and subsequent epilepsy is the systemic injection of pilocarpine in rodents (1). Treatment of rats and mice with low doses of lithium chloride (LiCl, 3 mEq/kg), followed by pilocarpine (30 mg/kg) or with a high dose of pilocarpine alone (300-350 mg/kg), results in a severe seizure-brain damage syndrome. The use of LiCl was devised to improve animal survival, because with this combination, the dose of pilocarpine can be decreased by about 10-fold. Since pilocarpine acts on muscarinic receptors (2) and its convulsant actions are evoked in the presence of the peripherally acting muscarinic antagonist, methyl-scopolamine (1), the activation of the cholinergic system by pilocarpine in the brain is believed to be the initiating factor for triggering seizures. Various studies have characterized pilocarpine-induced seizures using both EEG analysis and behavioral observations. Although there is still debate on the initiation site(s) of seizures (i.e., the hippocampus and related limbic regions vs ventral forebrain) and the involvement of brain regions in neuropathology (i.e., the hippocampus as compared to predominant neocortical damage), these initial studies nevertheless garnered a consensus among basic scientists that this model is representative of temporal lobe epilepsy precipitated by convulsive status epilepticus.Recently, novel findings raise the possibility that pilocarpine-induced seizures are not only the result of a d...

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“…It has been demonstrated that NO may facilitate the release of excitatory transmitters, possibly through a presynaptic cyclic GMP-dependent mechanism (Wu et al, 1997). The influences of NO of the central nervous system (CNS) on several physiological parameters such as salivary secretion have been demonstrated (Saad et al, 2002a(Saad et al, , 2003. Also these effects implicated the participation of septal area (Saad et al, 2002b).…”

Section: Introductionmentioning

confidence: 99%