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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excitatory amino acid transmitters participate in normal synaptic transmission throughout the CNS (see Headley and Grillner, May TiPS), so it comes as no surprise that such excitatory pathways are involved in the initiation of seizures and their propagation. Most attention has been directed to synapses using NMDA receptors, although more recent evidence indicates potential roles for the AMPA receptors as well. In this article--the first of two to focus on the neurological dangers inherent in excitatory amino acid pathways--Raymond Dingledine, Chris McBain and James McNamara consider their involvement in epilepsy; next month's article will cover brain damage following ischemia and hypoxia.
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PMID:Excitatory amino acid receptors in epilepsy. 216 4

To better understand and treat painful conditions, one needs to identify the cause, discover the source, and develop knowledge of peripheral and central pain transmission; headaches are no exception. The development of appropriate animal models is important. Accordingly, we have reviewed the anatomy, neurochemistry, electrophysiology, and pharmacology of the trigeminovascular system in experimental animals and emphasized whenever possible the relevance of this final common pathway to migraine, cluster, and other headache syndromes in humans. For example, based on recent anatomic dissections, the pericarotid cavernous sinus plexus was suggested as an important focus to investigate cluster headache pathophysiology. This plexus is an anatomic point of convergence for the nerves giving rise to the signs of sympathetic and parasympathetic activity and sensory symptoms that develop in cluster patients. As in other nociceptive systems, trigeminovascular axons assume at least two important roles. One concerns the transmission of nociceptive information. Electrophysiologic evidence supports the trigeminal nucleus caudalis as an important site for the convergence of visceral (vessel) and somatic (forehead) inputs to mediate the referral of vascular pain to superficial tissues. A second important role concerns the initiation of local increases in blood flow and enhanced protein permeability (sterile inflammation) via the axonal release of vasoactive neuropeptides. Plasma extravasation develops within the dura mater following trigeminal stimulation. Extravasation can be blocked by the administration of ergot alkaloids or sumatriptan, a new serotonin-like agonist, and a prejunctional (neuronal) mechanism of action for these drugs (such as blockade of release) was suggested based on experimental evidence. Whether vasoconstriction also relates to the therapeutic efficacy remains to be determined. As in other organ systems, real or threatened tissue injury provides an important stimulus for depolarizing sensory fibers. The stimulus may come from external conditions such as reduced blood flow or hypoglycemia. The brain may also possess intrinsic neuronal mechanisms by which nociceptors may be synthesized (e.g., glutamate-induced neurotoxicity, seizures). Molecules of relevance include bradykinin, prostaglandins, leukotrienes, and potassium. Experimental evidence was presented demonstrating that the trigeminal nerve mediates hyperemia within cortical gray matter by axon-reflex like mechanisms. An important role for this nerve was established during the hyperemic period of recirculation after ischemia or during severe hypertension above the limits of autoregulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Basic mechanisms in vascular headache. 217 82

This review has attempted to indicate areas of investigation that in vivo MRS methodology is particularly suited for and would answer important questions related to neonatal cerebral development or injury. There are several metabolites (PEth, PCr, NAA, taurine, glutamate) and lipids detectable by in vivo 31P or 1H MRS, which show substantial changes in concentration during ontogenesis. Do these biochemical markers correlate with major morphological changes, such as myelination? If they do, can this be used to quantitate abnormalities in brain development from congenital abnormalities or metabolic encephalopathies? In the neutral to mild acidic range (7.0 greater than pHi greater than 6.5) adult and neonatal brain appear to have similar intrinsic physicochemical buffering capacity. However, at the extremes of pHi induced by respiratory alkalosis or severe acidosis from partial ischemia, the possibility exists that the buffering capacities of adult and neonatal brain differ. Whether this is true requires further investigations using both neonates and adults, or perhaps more preferably, multiple measurements on a single species throughout its developmental period. Such studies are now feasible because multinuclear in vivo MRS can provide a large body of information from individual animals. A similar study design could prove useful for investigations of changes in cerebral resistance to hypoxia, ischemia, or asphyxia during development. The roles that blood pressure, glucose, temperature, or the administration of extrinsic buffers and drugs have on modulating the severity of and relationship between changes in blood flow, energy metabolites, or pHi, are all amenable to study using in vivo MRS. Furthermore, all of these variables can be measured simultaneously. The kinetics of brain acid and lactate homeostasis during chronic cerebral insults or following acute insults has not been thoroughly examined in either neonates or adult animals. There is evidence to suggest that following ischemia or seizures, brain acidosis resolves before brain lactosis. However, the clinical diagnostic significance of this post-insult uncoupling between pHi and lactate remains to be established. Finally, the application of in vivo MRS methodology to study the effects of trauma, drugs, environmental toxins, and other metabolic encephalopathies on neonatal cerebral perfusion and metabolism are virtually unexplored. Hopefully, the material presented here will prompt researchers to consider the application of in vivo MRS to new avenues of investigation.
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PMID:In vivo multinuclear magnetic resonance spectroscopy investigations of cerebral development and metabolic encephalopathy using neonatal animal models. 219 84

Epilepsy complicates severe head trauma. Development of persistent seizures appears to correlate with the extent of trauma. Although early reports suggested that prophylactic administration of antiepileptic drugs would prevent epileptogenesis, controlled studies have failed to corroborate this assumption. Head trauma initiates a sequence of responses that includes altered blood flow and vasoregulation, disruption of the blood-brain barrier, increases in intracranial pressure, focal or diffuse ischemia, hemorrhage, inflammation, necrosis, and disruption of fiber tracts. The presence of an intracranial hematoma has a robust association with the development of post-traumatic epilepsy. Extravasation of blood is followed by hemolysis and deposition of heme-containing compounds into the neuropil, initiating a sequence of univalent redox reactions and generating various free radical species, including superoxides, hydroxyl radicals, peroxides, and perferryl ions. Free radicals initiate peroxidation reactions by hydrogen abstraction from methylene groups adjacent to double bonds of fatty acids and lipids within cellular membranes. Intrinsic enzymatic mechanisms for control of free radical reactions include activation of catalase, peroxidase, and superoxide dismutase. Steroids, proteins, and tocopherol also terminate peroxidative reactions. Tocopherol and selenium are effective in preventing tissue injury initiated by ferrous chloride and heme compounds. Treatment strategies for prevention or prophylaxis of post-traumatic epilepsy must await absolute knowledge of mechanisms. Antioxidants and chelators may be useful, given the speculation that peroxidative reactions may be an important component of brain injury responses. However, potential treatment strategies involving gamma-aminobutyric acid (GABA) agonists, NMDA receptor antagonists, and barbiturates need further scientific assessment.
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PMID:Post-traumatic epilepsy: cellular mechanisms and implications for treatment. 222 73

The increased vulnerability of animals fed a magnesium (Mg)-deficient (MD) diet to ischemia-induced myocardial necrosis has been attributed to changes in myocardial electrolyte metabolism. However, a variety of hematologic changes have also been reported in MD and some of these, such as an increase in platelet aggregability, may contribute to the increased myocardial vulnerability. In the present study, we quantified the effect of MD on platelet and megakaryocyte abundance as well as on platelet aggregability with and without an administered calcium channel blocker (nifedipine). Hamsters were fed either a "minimal Mg" diet, in which the level of Mg was kept just high enough to prevent seizures, or a "preset Mg" diet containing precisely known amounts of Mg. Animals fed the minimum Mg diet showed an initial increase in the platelet count, which returned to control range when the dietary Mg was increased to 9 mmoles/kg. Animals on the preset Mg diet showed an increased platelet count if the Mg level was 10 mmoles/kg or less. In addition to the increase in number, platelets from MD animals were less responsive to the aggregation-inhibiting effect of nifedipine than were platelets from control animals, although MD itself did not result in an increased aggregability under the conditions used here. Animals with an increase in circulating platelets showed decreased megakaryocyte abundance in the femoral marrow, but megakaryocytes that were present were larger than those in control animals. These results indicate a profound effect of dietary Mg deficiency on platelet biology. The observed changes could contribute to the increase in myocardial vulnerability to injury found in MD animals.
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PMID:Effects of reduced dietary magnesium on platelet production and function in hamsters. 223 16

Involvement of neuroexcitatory mechanisms in cerebral ischemia and brain injury was explored in experimental models of repetitive forebrain ischemia by temporary occlusion of carotid arteries in gerbils and cryogenic injury to the cerebral cortex in rats and gerbils. Our observations in these models revealed a pattern of injury that involved some anatomic structures outside the areas of direct ischemic or traumatic insult. Such foci of injury revealed conspicuously abnormal uptake of 45Ca associated with slight or moderate neuronal alteration, whereas severely injured areas showed no 45Ca uptake. Electron microscopic observations revealed a characteristic presence of calcium in swollen dendrites, closely resembling pictures obtained in neuroexcitatory conditions such as epileptic seizures. Abnormal uptake of 45Ca was associated with apparent blood-brain barrier changes characterized by intracytoplasmic uptake of extravasated albumin into the neurons. Protein synthesis assayed by in vivo [3H]leucine incorporation was reduced in regions showing calcium accumulation. Our observations suggest that neuroexcitation may play an important role in development of secondary and chronic changes after ischemic or traumatic brain insults.
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PMID:Putative neuroexcitation in cerebral ischemia and brain injury. 223 87

A 3-year-old child with minimal change nephrotic syndrome (MCNS) developed an acute hypertensive encephalopathy characterized by coma, focal seizures, right hemiparesis, global aphasia and cortical blindness. Episodic hypertension and seizures persisted for 24 h despite intervention with antihypertensive and anticonvulsant therapy. Clinical suspicion of cortical blindness was confirmed by visual-evoked potential studies. CT scans performed 14 and 21 days after the acute episode demonstrated symmetric occipital white matter lucencies compatible with ischemia and/or associated edema. Hypertensive encephalopathy with cortical blindness and symmetric white matter hypodense lesions visualized on CT scan have recently also been described in eclampsia of pregnancy. This report documents an unusual acute hypertensive encephalopathy in childhood MCNS, unassociated with membranoproliferative glomerulonephritis, or progressive focal glomerulosclerosis.
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PMID:Acute hypertensive encephalopathy in minimal change nephrotic syndrome. 225 60

8319, ((+-)-2-Amino-N-ethyl-alpha-(3-methyl-2-thienyl)benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced [3H] TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia.
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PMID:Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist. 229 Aug 51

Heterogenous stock mice in addition to mice selectively bred to maximally differ in their severity of alcohol withdrawal seizures (withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP] were used to provide evidence in favor of the importance of the rapidly changing distribution of brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) (HK). An ischemic response at 15, 30, 60 and 120 s after killing showed a decreasing cerebellar cytosolic HK concentration of 31%, 15%, 14% and 10% while the cerebral concentrations were 23%, 13%, 13% and 14%, respectively. WSR and WSP mice given an acute i.p. dose of 4 g/kg of alcohol showed opposite HK responses. Cytosolic HK in WSR mice decreased 18.5%, while WSP mice showed an increase of 20.3% over paired saline-injected controls. When ischemia was allowed to proceed in WSP mice following an in vivo alcohol treatment, cytosolic HK decreased in parallel to mice not given alcohol. These data suggest that alcohol can cause an HK redistribution in vivo which could play a role in the differing sensitivities of WSR and WSP mice to alcohol related seizures.
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PMID:Hexokinase redistribution in vivo. 232 57

Silver impregnation performed 1-2 days after transient forebrain ischemia in the Mongolian gerbil demonstrated terminal-like granular deposits in the outer two-thirds of the hippocampal dentate molecular layer (perforant path terminal zone), even though neither the cell bodies of origin of the perforant path nor the dentate granule cells were destroyed. Electron microscopic studies of the dentate gyrus were performed in an effort to discover the identity of these degenerating structures. Electron microscopy revealed that the granular silver deposits corresponded to electron-dense profiles. Many of these were degenerating boutons and some were degenerating postsynaptic dendritic fragments, but most of them could not be identified with certainty. Electron-dense profiles were less numerous than expected from the density of granular silver deposits. These structures were probably the degenerating axons, axon terminals and dendrites of CA4 neurons. The granular silver deposits and electron-dense boutons observed in the inner third of the dentate molecular layer 5 days after transient ischemia can probably be explained by the ischemia-induced degeneration of CA4 mossy cells, which give rise to the dentate associational-commissural projection. Finally, most mossy fiber boutons in area CA4 and some boutons in the molecular layer appeared watery and enlarged on postischemia days 1 and 2. Mossy fiber boutons with this ultrastructural appearance have previously been observed in seizure-prone animals and in animals undergoing convulsant-induced seizures. Although no postischemic seizures occur under the conditions of this study, these findings support the idea that excitatory pathways become hyperactive after transient ischemia.
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PMID:Electron microscopic study of the gerbil dentate gyrus after transient forebrain ischemia. 233 92


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