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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1987, an intoxication by cultured mussels produced neurological problems, such as headache, confusion, and loss of memory, particularly severe at times. Neuronal damage was found in the hippocampus and amygdala of four patients. The intoxication was attributed to the presence in mussels of domoic acid, a rare excitatory amino acid acting at the non-NMDA receptor. We now report that a domoic acid-containing mussel extract is more neurotoxic for cultured neurons than purified domoic acid. Moreover, we show that this increase in neurotoxicity is selectively due to domoic acid potentiation of the excitotoxic effect of glutamic acid and aspartic acid present in high concentrations in mussel tissue. We also show that subtoxic concentrations of domoic acid are sufficient to potentiate glutamic acid and aspartic acid neurotoxicity, and we present evidence suggesting that the neurotoxic synergism may occur through a reduction of the voltage-dependent Mg2+ block at the NMDA receptor-associated channel, following activation of non-NMDA receptors by domoic acid. Thus, based on our results, we suggest that the contemporary presence in the brain of concentrations of domoic acid insufficient alone to be toxic, together with excitatory amino acids, of endogenous and eventually of diet-related origin, may have been relevant in the occurrence of the neurological problems reported.
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PMID:Domoic acid-containing toxic mussels produce neurotoxicity in neuronal cultures through a synergism between excitatory amino acids. 135 95

Cavernous angiomas are vascular malformations that cause neurodegeneration and symptoms including epileptiform seizures, headache, and motor deficits. Following neurosurgical removal of the angiomas, patients mostly recover well and become seizure-free. This study reports on the levels of certain amino acids in angiomas, obtained from 13 patients. Distinct zones of the angiomas were analyzed, from the thrombotic core, via gliotic, hemosiderin-infiltrated intermediate zones, to a periphery without macroscopic abnormalities. The neurotransmitter amino acids glutamate, aspartate, and GABA as well as phosphoethanolamine displayed decreasing levels from the periphery to the core, reflecting the gradual neuronal loss. Compared with normal brain tissue, there was a marked increase in the levels of serine (fivefold), glycine (10-fold), and ethanolamine (20-fold) in the peripheral zone of the cavernous angiomas. The results are discussed in relation to seizures and NMDA receptor activation, neuron-glia interactions, membrane phospholipids, and blood-brain barrier function.
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PMID:High levels of glycine and serine as a cause of the seizure symptoms of cavernous angiomas? 866

The marshland plant Cyperus articulatus (Cyperaceae) is commonly used in traditional medicine in Africa and Latin America to treat a wide variety of human diseases ranging from headache to epilepsy. We tested the hypothesis that the purported anti-epileptic effect of this plant might be due to a functional inhibition of excitatory amino acid receptors. One or several component(s) contained in the extracts inhibited the binding of [3H]CGP39653 to the NMDA recognition site and of [3H]glycine to the strychnine-insensitive glycine site of the NMDA receptor complex from rat neocortex. Water extracts from rhizomes of Cyperus articulatus dose-dependently reduced spontaneous epileptiform discharges and NMDA-induced depolarizations in the rat cortical wedge preparation at concentrations at which AMPA-induced depolarizations were not affected. We conclude that the purported beneficial effects of Cyperus articulatus might at least partially be due to inhibition of NMDA-mediated neurotransmission.
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PMID:Extracts from rhizomes of Cyperus articulatus (Cyperaceae) displace [3H]CGP39653 and [3H]glycine binding from cortical membranes and selectively inhibit NMDA receptor-mediated neurotransmission. 895 23

Our previous studies indicating that the function of excitatory amino acids, NMDA type receptor, is modulated by serotonin focused on the interaction between serotonin 5HT1B/1D and glutamate, NMDA receptor in brain cortex. The effect of agonists of 5HT1B/1D receptor, sumatriptan, and zolmitriptan on NMDA receptor-evoked activation of nitric oxide (NO) and cGMP synthesis in adult rat brain cortex slices was investigated. Two kinds of experiment were carried out using adult rats. In one of them, sumatriptan or zolmitriptan was administered in vivo subcutaneously (s.c.) in a dose of 0.1 mg per kg body weight. Brain slices were then prepared and used in the experiments or, in the other exclusively in vitro studies, both agonists at 10 microM concentration were added directly to the incubation medium containing adult rat brain cortex slices. The data obtained from these studies indicated that stimulation of NMDA receptor in brain cortex slices leads to a large increase in calcium, calmodulin-dependent NO synthase (NOS) activity and to significant enhancement of the cGMP level. This NMDA receptor-dependent NO and cGMP release was completely blocked by competitive and noncompetitive NMDA receptor antagonists APV (10 microM) or MK-801 (10 microM.), respectively. The specific inhibitor of Ca(2+)-dependent isoforms of NOS (N-nitro-1-arginine NNLA and 7-nitroindozole (7-N1)) eliminated the NMDA receptor-mediated enhancement of NO and cGMP release. Moreover, the serotonin 5HT1B/1D receptor agonists sumatriptan and zolmitriptan administrated in vivo (s.c.) or in vitro abolished NMDA receptor-evoked NO signalling in brain cortex. The potency of both agonists investigated directly in vitro was similar to their effect after in vivo administration. These results suggest that both serotonin 5HT1B/1D receptor agonists may play an important role in modulating the NO and cGMP-dependent signal transduction pathway in the brain. This effect of sumatriptan and zolmitriptan on NO signaling in the brain system should be taken into consideration when investigating their mechanism of action in the migraine attack.
Cephalalgia 1999 Dec
PMID:Serotonin 5HT1B/1D receptor agonists abolish NMDA receptor-evoked enhancement of nitric oxide synthase activity and cGMP concentration in brain cortex slices. 1066 4

Expression of Fos protein is an indicator of neuronal perturbation and is readily observed in the caudal medulla and the spinal cord following trigeminovascular nociceptive activation by electrical stimulation of the superior sagittal sinus (SSS) in the cat. It has been shown in the rat that N-methyl-D-aspartate (NMDA) receptor blockade causes a reduction in Fos protein expression after generalised meningeal irritation. We wished to examine if the same relationship was true in the cat, using the same non-competitive NMDA receptor antagonist MK-801, and a trigeminovascular-specific stimulus. A group of experimental animals underwent stimulation following blinded administration of MK-801 (4 mg/kg i.v.); control animals underwent stimulation minus MK-801, and a non-stimulated control animal underwent surgery alone. The regions examined for Fos-like immunoreactivity were the trigeminal nucleus caudalis (TNC) and its caudal extension into the C(1) and C(2) levels of the upper cervical spinal cord. The Fos-positive cell counts for the three regions (TNC, C(1) and C(2)) were grouped together for analysis. In the control stimulated group a median of 78 (56-99, quartile range, n=4) cells were Fos-positive. In the group treated with MK-801 the median number of Fos-positive cells was reduced to 40 (30-48; P<0.03, n=7). The large reduction that was observed in SSS stimulation-evoked Fos protein expression following the administration of MK-801, taken together with electrophysiological data, indicates a role for glutamate in neurotransmission within the trigeminocervical complex. Understanding glutamatergic mechanisms in the trigeminocervical complex offers mechanistic insight and therapeutic possibilities for primary neurovascular headaches, such as migraine.
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PMID:The NMDA receptor antagonist MK-801 reduces Fos-like immunoreactivity within the trigeminocervical complex following superior sagittal sinus stimulation in the cat. 1143 Aug 92

Magnesium is a physiological N-methyl-D-aspartate (NMDA) antagonist. The NMDA receptor may be involved in the pathogenesis of acute mountain sickness (AMS). In the present study, healthy subjects were randomized to receive either 400 mg of oral magnesium citrate (16 mmol) or matching placebo every 8 h for 5 days (prevention trial). Subjects then climbed to 4559 m in approx. 24 h and stayed there for 48 h. A Lake Louise Score <3 at any time was defined as the absence of AMS, whereas a score >6 (with ataxia, headache and nausea) was defined as a prevention failure. In a subsequent trial (treatment trial), subjects with a Lake Louise Score >6 (with ataxia, headache and/or nausea) were randomized to receive either 4 g of intravenous magnesium sulphate (16 mmol) or matching placebo. A decrease in the score >50% within 60 min was regarded as a treatment success. Dichotomous data were analysed using relative risk (RR) or odds ratio (OR), and continuous data using Student's t test or Wilcoxon's rank-sum test. In the prevention trial, data from 61 subjects (30 receiving magnesium and 31 placebo) were analysed. With oral magnesium, 20% of subjects had no AMS compared with 16.1% in the placebo group [RR (95% CI), 1.2 (0.4-3.6); where CI is confidence interval]. With magnesium, 40% were prevention failures compared with 35.5% in the placebo group [RR (95% CI), 1.13 (0.59-2.15)]. The mean time to failure and severity of AMS was similar between the two groups. With magnesium, 38.2% had loose stools compared with 11.8% in placebo group [RR (95% CI), 3.25 (1.18-8.97)]. In the treatment trial, 12 subjects received magnesium and 13 received the placebo. With intravenous magnesium, 25% were regarded as treatment successes compared with none in the placebo group [OR (95% CI), 9.71 (0.91-103.4)]. With magnesium, mean (+/- S.D.) scores decreased from 11.6 +/- 1.7 before treatment to 9.0 +/- 3.5 after treatment (P=0.009); scores remained unchanged in the placebo group. With magnesium, 75% of subjects experienced a transient flushing compared with 7.7% in the placebo group [RR (95% CI), 0.05 (0.01-0.25)]. In conclusion, oral magnesium does not prevent AMS. In subjects with established AMS, intravenous magnesium reduces the severity of symptoms to some extent, but this effect is of no clinical importance.
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PMID:Magnesium for the prevention and treatment of acute mountain sickness. 1457 5

The tricyclic antidepressant amitriptyline is the only documented and most widely used prophylactic drug for chronic tension-type headache (CTTH). However, it is not fully clarified whether the serotonin (5-HT) reuptake inhibition plays a major role for the analgesic effect of amitriptyline. To explore the importance of 5-HT reuptake inhibition for mechanism of action of the analgesic effect of amitriptyline we investigated platelet 5-HT levels during preventive treatment of CTTH with amitriptyline, the selective serotonin reuptake inhibitor citalopram, and placebo. Thirty-four patients with CTTH were given preventive treatment with amitriptyline 75 mg/day, the selective 5-HT reuptake inhibitor citalopram 20 mg/day, and placebo in a 32-week, double-blind, placebo-controlled, three-way crossover trial. Blood samples were collected in the last week of each treatment period. Platelet 5-HT was used as a measure of 5-HT reuptake inhibition and determined by high performance liquid chromatography. Area under the headache curve was 308 (157-715) (median with quartiles in parentheses) with amitriptyline and significantly lower than 377 (158-1121) with citalopram (P = 0.04) and 441 (178-1408) with placebo (P = 0.002). There was no difference between citalopram and placebo (P = 0.23). Platelet 5-HT was 0.4 (0.3-0.7) x 10(-18)mol/platelet with citalopram, which was significantly lower than 1.7 (1.2-2.4) x 10(-18)mol/platelet with amitriptyline (P < 0.001), and 3.5 (2.8-4.3) x 10(-18)mol/platelet with placebo (P < 0.001). The lower platelet 5-HT during treatment with citalopram than amitriptyline indicates that 5-HT reuptake was most effectively inhibited by citalopram. In contrast, amitriptyline was most effective in reduction of headache. This suggests that the analgesic effect of amitriptyline in CTTH is not solely due to 5-HT reuptake inhibition and that other mechanisms such as norepinephrine reuptake inhibition, NMDA receptor antagonism, blockade of muscarinic receptors and ion channels should be addressed in the future research.
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PMID:Analgesic effect of amitriptyline in chronic tension-type headache is not directly related to serotonin reuptake inhibition. 1510 13

Stimulation of the greater occipital nerve produces excitation of second order neurons in the trigeminocervical complex. Given that neck pain is very common in primary headache disorders, this convergent excitation may play a role in pain referral from cervical structures. While previous studies have demonstrated a physiological model for this convergence, this study sought an anatomical approach to examine the distribution of second order neurons in the trigeminocervical complex receiving greater occipital nerve input. In addition, the role of glutamatergic NMDA receptor activation within the trigeminocervical complex in response to cervical afferents was studied. Noxious stimulation of the occipital muscle in rat using mustard oil and mineral oil produced significantly altered Fos expression in the trigeminocervical complex compared with the surgical control (H(4)=31.3, P<0.001, Kruskal-Wallis). Baseline expression was 11 (median, range 4, 17) fos positive cells in the trigeminocervical complex, occipital muscle treated with mustard oil produced 23 (17, 33) and mineral oil a smaller effect of 19 (15, 25) fos positive cells, respectively (P=0.046). The effects of both mustard and mineral oil were reversed by the NMDA-receptor antagonist MK801. This study introduces a model for examining trigeminocervical complex activity after occipital afferent stimulation in the rat that has good anatomical resolution and demonstrates involvement of glutamatergic NMDA receptors at this important synapse.
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PMID:Occipital afferent activation of second order neurons in the trigeminocervical complex in rat. 1673 Jan 24

We report here studies on the levels of autoantibodies (aAb) to AMPA glutamate receptors (GluR1 subunit) and NMDA glutamate receptors (NR2A subunit) in serum from 60 children aged 7-16 years with chronic posttraumatic headache (CPTHA) following mild craniocerebral trauma (CCT). The first group consisted of 48 children who had sustained cerebral concussion (CC), of which 34 had single-episode CC (subgroup 1a) and 14 had repeated CC (subgroup 1). The second group included 12 children with mild cerebral contusions (MCC). Serum glutamate receptor aAb levels were measured six months and one year after trauma. Increased aAb levels were expressed as percentages and were regarded as significant when increases were to 120% of the level seen in healthy children of the same age. The highest levels of aAb to NMDA receptors were seen in children with MCC (165 +/- 34%) and single CC (145 +/- 12.6%). Children with repeated CC had NMDA receptor aAb at normal levels (108 +/- 12.4%). Increases in NMDA receptor aAb were seen during the first year after trauma. Increases in AMPA receptor aAb were seen in children with repeated CC and MCC (150 +/- 16.8% and 167 +/- 31.3%). EEG studies showed that 18% of these children had nonspecific paroxysmal changes and 6% showed epileptiform activity. These results provide evidence that children with post-traumatic headache demonstrated hyperstimulation of glutamate receptors and overdevelopment of the autoimmune process. Increases in serum levels of aAb to NMDA glutamate receptors reflected hypoxic-ischemic brain lesions in children with CPTHA and dictate the need for these children to receive metabolic therapy.
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PMID:Glutamate receptor autoantibody concentrations in children with chronic post-traumatic headache. 1792 39

We present the case of a woman with chronic migraine who unexpectedly reported full remission of headache after memantine, an NMDA receptor antagonist, was administered for treating concomitant mild cognitive impairment. An underlying dose-dependent effect of memantine on headache symptoms in chronic daily headache and chronic migraine could be assumed.
Headache 2008 Feb
PMID:Memantine and NMDA antagonism for chronic migraine: a potentially novel therapeutic approach? 1854 63


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