Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following sequential intraocular transplantations of areas containing NE cell bodies (locus coeruleus or superior cervical ganglion) and of NE fiber target areas (hippocampus), both pieces mature in a manner analogous to that observed for individual transplants. NE-containing nerve fibers, derived from either LC or SCG transplants, can be seen to invade the hippocampal formation. When LC is used, the invading fibers markedly hyperinnervate the hippocampus while SCG-derived fiber densities approximate those seen with innervation from the adrenergic ground plexus of the iris. Electrophysiological recordings from neurons in the LC reveal an atropine-sensitive excitatory response to illumination, suggesting innervation of the LC by cholinergic nerve fibers from the iris. This is supported by the fact that dense cholinesterase-positive staining can be found in the LC piece. Application of an epileptogenic agent, such as penicillin, results in a marked excitation of neurons in the LC without inducing epileptiform activity in the hippocampus. In contrast, single hippocampal grafts seize readily after penicillin. Local application of the inhibitory agent GABA into the LC allows penicillin-induced epileptiform activity to generate in the hippocampus, suggesting that functional inhibitory innervation develops between NE fibers derived from LC and pyramidal neurons in the hippocampus. Supporting this, subsequent excitation of LC neurons by iontophoresis of glutamate terminates the hippocampal seizure. Prior administration of reserpine (2.5 mg/kg) disrupts the inhibitory influence of LC innervation on the hippocampal EEG following penicillin. After reserpine, the hippocampal portions of double grafts behave like single hippocampal transplants. It is concluded that sequential transplantations of cell body and target regions of the CNS to the anterior chamber of the eye creates a functional, yet isolated, neuronal pathway which can be utilized to study the development of neuronal connections.
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PMID:Conditions for adrenergic hyperinnervation in hippocampus: II. Electrophysiological evidence from intraocular double grafts. 739 24

Kainic acid (KA) was injected into the amygdala (AM) complex of the rat and its effect on the cholinergic enzymes, choline acetyltransferase (CAT) and acetylcholinesterase (AChE), and the binding of the muscarinic ligand, [3H]quinuclidinyl-benzilate (QNB) and the nicotinic ligand [125I]alpha-bungarotoxin (aBuTX) was investigated. Ka produced a loss of approximately 35% of the CAT activity in the AM. However, no effect on AChE activity was observed. A 30--50% decrease in the number of muscarinic and nicotinic receptor sites was also found. CAT, AChE and QNB binding in the AM contralateral to the injection did not change. However, the binding of aBuTX was found to decrease by approximately 40%. The present results suggest that the loss of CAT activity in the AM after treatment with KA is due to the destruction of cholinergic neurons within the AM. The lack of effect on AChE suggests that the major cholinergic input to the AM is not affected by KA. In addition, the loss of nicotinic receptors in the contralateral AM may reflect anterograde degeneration of terminals that have nicotinic sites located on them, or may be secondary to the elicitation of intense seizure activity evoked by the KA.
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PMID:The effect of kainic acid on cholinergic enzymes and receptors in the amygdala complex of the rat. 740 18

Monkeys were exposed to varying doses of soman and given therapy. Therapy consisted of pyridostigmine, clonazepam, atropine and HS-6 or HI-6. Cerebral electrical activity, heart rate, respiration, systemic blood pressure and cholinesterase activity were recorded thoughtout the experiment. The animals in the HS-6 series were divided into 4 groups depending upon the dose of soman; one group received 30 microgram/kg of soman, the second group received 40 microgran/kg. All animals in the HI06 series survived while only one of three monkeys in the fourth group survived. Administration of therapy immediately suppressed all seizure activity and convulsions and the animals appeared awake throughout the experiment. All animals exhibited bradycardia and hypotension following the adminstration of therapy. The cholinesterase activity was depressed after administration of HS-6 therapy. Three of the four monkey that received therapy consisting of HI-6 at a dose of 15 mg/kg survived, while one of two that received HI-6 at a dose of 30 mg/kg survived. The animals that received HI-6 at a dose of 15 mg/kg did not exhibit as severe a decrease in blood pressure as the animals in either the HS-6 series or the monkeys that received HI-6 at 30 mg/kg. In addition, these monkeys were awake and appeared alert throughout the experiment and were up within 4-6 hr post-exposure to soman. The animals that received 30 mg/kg exhibited severe hypotension and did poorly.
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PMID:comparison of the efficacy of HS-6 versus HI-6 when combined with atropine, pyridostigmine and clonazepam for soman poisoning in the monkey. 744 43

L-Huperzine-A (Hup-A), a natural cholinesterase inhibitor (ChEI) derived from the Chinese herb Huperzia serrata, was administered systemically (i.p.) or locally through the microdialysis probe into the rat cortex. Systemic Hup-A significantly increased acetylcholine (ACh) levels above baseline at doses of 0.1, 0.3, and 0.5 mg/kg; the increases were 54%, 129%, and 220%, respectively. Norepinephrine (NE) and dopamine (DA) levels were also increased 121% and 129% above baseline at 0.3 mg/kg, and 143% and 153% at 0.5 mg/kg. Peak cholinesterase (ChE) inhibition was 23% at 60 min with the 0.3 mg/kg dose. Huperzine-A, perfused through the microdialysis probe, produced a maximal increase of ACh levels of 3090% and 7790% at concentrations of 5 and 50 microM. The ACh increase seen at both concentrations lasted at least 6 hr. At the 5-microM dose, NE and DA were increased by 214% and 386%; at the 50-microM dose, NE and DA were increased by 216% and 1141%. There were no changes of 5-HT levels. With local administration (via the probe), both doses produced facial-forelimb seizures that lasted throughout the perfusion. Our results show that Hup-A is a potent inhibitor of ChE which penetrates into the brain and produces a dose-dependent increase of ACh, NE, and DA in rat cortex. This effect is seen with both systemic and local intracerebral administration, suggesting cortical as well as subcortical effects of the drug.
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PMID:Second generation cholinesterase inhibitors: effect of (L)-huperzine-A on cortical biogenic amines. 750 Mar 84

We recently reported that systemic administration of the anticholinesterase, soman, caused rapid depletion of forebrain norepinephrine (NE) in convulsive but not in nonconvulsive rats. As neurons in nucleus locus coeruleus (LC) provide the bulk of NE innervation to most of the forebrain and the sole source of NE input to the cortex and the olfactory bulb, soman-induced NE depletion was hypothesized to result from activation of LC neurons. This activation was thought to be due to inhibition of acetylcholinesterase by soman, leading to rapid, sustained accumulation of acetylcholine in LC, causing these cells to fire at a high sustained rate. Support for this hypothesis was provided by neurophysiological findings showing that: (i) Systemic administration of soman in anesthetized rats caused a sustained, fivefold increase in the mean firing rate of LC neurons and (ii) microinjections of soman directly into LC caused a similar increase in the firing rate of LC neurons. Soman-induced activation of LC occurred prior to and even in the absence of seizures. As systemic administration of the muscarinic receptor antagonist, scopolamine, rapidly and completely reversed soman-induced activation of LC, it was further hypothesized that activation of LC neurons following soman administration is due to muscarinic receptor stimulation. The rapid release of NE by cholinolytic agents, thus, may play an important role in the initiation and/or maintenance of convulsions. To further test the hypothesis that NE release in soman-intoxicated rats is due to muscarinic activation of LC, we have investigated the effects of the muscarinic receptor agonist, pilocarpine, on NE release and LC discharge. In one set of experiments, rats were injected with a periconvulsive dose of pilocarpine (300 mg/kg, ip); both convulsive and nonconvulsive rats were sacrificed between 1 and 96 h and monoamine levels in the rostral forebrain and olfactory bulb were determined by HPLC with electrochemical detection. NE levels declined substantially only in convulsive rats; forebrain NE levels in convulsive rats rapidly decreased to 50% of control levels at 1 h and to 37% of controls level between 2 and 4 h. The time course and magnitude of these changes were similar to those observed following soman administration in our previous study. Recovery of forebrain NE began at 8 h and was complete by 96 h following pilocarpine administration. Neither dopamine (DA) nor serotonin (5-HT) levels were changed in the forebrain and olfactory bulb of either convulsive or nonconvulsive rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pilocarpine-induced convulsions in rats: evidence for muscarinic receptor-mediated activation of locus coeruleus and norepinephrine release in cholinolytic seizure development. 768 35

The protection afforded by TCP (thienylcylohexylpiperidine), a non-competitive blocker of N-methyl-D-aspartate (NMDA) receptors, against the seizures and lethality produced by 2 x LD50 of soman (62 micrograms/kg, sc), an irreversible inhibitor of cholinesterase, was studied in guinea-pigs. In the presence of additional anticholinergic medication (pyridostigmine: 0.2 mg/kg, sc, 30min prior to soman; atropine sulphate: 5mg/kg, im, 1 min post-soman), TCP pretreatment (2.5mg/kg, im, 30 or 15 min prior to soman) did not generally prevent the appearance of soman-induced status epilepticus but did arrest it after 30-40 min in 80% (TCP-30min) or 100% (TCP-15min) of the convulsing subjects. Moreover, in all subjects treated curatively, TCP was able to interrupt ongoing status epilepticus in approximately 20, 10 or 8 min when it was administered 5, 30 or 60min respectively after the onset of epileptiform tracings on EEG. All of these curatively administered animals survived and recovered remarkably well. On every criteria examined (latency-to-seizure arrest, 24hr-survival rate, clinical recovery), injection of 2.5mg/kg TCP after 90min of seizures appeared slightly less efficient compared to earlier curative administration. Therefore, our study (a) establishes that the previously reported capacity of MK-801 (dibenzocyclohepneimine) to counteract soman toxicity is not unique and could be extended to other non-competitive inhibitors of NMDA receptors; (b) shows that TCP could easily prevent and, above all, interrupt soman-induced seizures; furthermore, TCP appears the first compound ever tested on soman poisoning that still displays satisfactory anticonvulsant activity after such a long duration of initial status epilepticus (90min); therefore, TCP might be of special value for the delayed therapy for soman poisoning; (c) confirms that NMDA receptors are involved in the maintenance of seizures and play an important role in other processes implicated in the overall toxicity (including the lethal respiratory effects) of soman poisoning.
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PMID:Anticonvulsant and antilethal effects of the phencyclidine derivative TCP in soman poisoning. 771 55

Congenital ornithine transcarbamylase (OTC) deficiency in humans is associated with seizures and mental retardation. As part of a series of studies to delineate the neurochemical features of OTC deficiency, activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), respectively, were measured in brain regions of the congenitally hyperammonemic sparse-fur (spf) mouse, a mutant with an X-linked inherited defect of OTC. ChAT activities were reduced by 63% (P < 0.01) in cerebral cortex of spf mice compared with CD-1/Y controls. Activities of the GABA nerve terminal marker enzyme, glutamic acid decarboxylase, on the other hand, were within normal limits. Using an immunohistochemical technique with a monoclonal antibody to ChAT, a significant loss of ChAT-positive neurons was observed throughout the cerebral cortex, septal area and diagonal band of spf mice. These results suggest that a loss of forebrain cholinergic neurons is a feature of congenital OTC deficiency in these mutants. Possible pathogenetic mechanisms responsible for the cholinergic neuronal loss in congenital OTC deficiency include neurotoxic effects of ammonia and accumulation of quinolinic acid.
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PMID:Evidence for cholinergic neuronal loss in brain in congenital ornithine transcarbamylase deficiency. 781 42

Previous studies have demonstrated that some of the molecular and morphological changes that are characteristic of reactive astrocytes are induced following seizures. This discovery provides the means to experimentally modify the time course and extent of reactive changes in astrocytes following injury and so explore how these reactive changes modulate other events in the injured nervous system. The present study evaluates whether superinduction of a reactive state in astrocytes alters one form of postlesion synaptic reorganization (the sprouting of cholinergic projections in the dentate gyrus after destruction of the entorhinal cortex). Cholinergic sprouting after entorhinal cortex lesions was evaluated in control mice and in mice that experienced electroconvulsive seizures (ECS) from the day of surgery until 12 days postlesion. Animals were prepared for acetylcholinesterase (AChE) histochemistry at 2, 4, 6, 8, 10, 12, 14, and 30+ days postlesion. Quantitative densitometric analyses revealed that the increase in AChE staining that is indicative of cholinergic sprouting was essentially eliminated in the animals that experienced daily ECS. These results indicate that the induction of electroconvulsive seizures during the postinjury period disrupts at least one form of postlesion synaptic reorganization that would otherwise occur. This disruption of synaptic reorganization may be a consequence of the induction of a persistent reactive state in astrocytes.
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PMID:Cholinergic sprouting is blocked by repeated induction of electroconvulsive seizures, a manipulation that induces a persistent reactive state in astrocytes. 792 32

Cholinergic drugs were shown to affect spike and wave discharges in a selected strain of Wistar rats with generalized non-convulsive absence epilepsy, named GAERS (Genetic Absence Epilepsy Rats from Strasbourg). The involvement of cholinergic transmission from the nucleus basalis in the control of absence seizures in GAERS was investigated in the present study, by examining the effects of unilateral excitotoxic lesions of this nucleus on the occurrence of spike-wave discharges. Ibotenate (0.01 M) and quisqualate (0.03 and 0.06 M)-induced lesions of the nucleus basalis suppressed spike-wave discharges in the cortex ipsilateral to the lesion. The suppression was associated with a disappearance of both acetylcholinesterase-fibres in the cerebral cortex and choline acetyltransferase immunopositive neurons within the nucleus basalis. Concomitantly, the background electroencephalographic activity was slowed. These results suggest that cholinergic innervation of the cerebral cortex by the nucleus basalis is involved in the occurrence of generalized non-convulsive seizures, in relation to the control of cortical activation.
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PMID:Nucleus basalis lesions suppress spike and wave discharges in rats with spontaneous absence-epilepsy. 800 7

Nerve agents, highly toxic organophosphorus cholinesterase inhibitors, inhibit acetylcholinesterase and cause an accumulation of acetylcholine. Clinical effects depend on the route and amount of exposure and include miosis, bronchoconstriction, excessive secretions, vomiting, seizures, and cessation of respiratory and cardiac activity. Eye effects include miosis, engorgement of ocular vessels, pain, and decrease in light sensitivity. Therapy consists of atropine, a cholinesterase reactivator (pralidoxime), and ventilation as needed.
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PMID:Clinical effects of organophosphorus cholinesterase inhibitors. 802 5


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