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

A new animal model for epilepsy was successfully produced by microinjection of cobaltous chloride into the lateral cerebral ventricle of the rat. The median convulsive dose (CD50) and the median lethal dose (LD50) of CoCl2 was 0.45 microM/10 microliters (0.27-0.77 microM/10 microliters) and 1.07 microM/10 microliters (0.73-1.57 microM/10 microliters), respectively. The behavioral changes, electrocorticogram (ECoG), and the action of 5 classical anticonvulsants were studied using this new model. Seizures induced by cobaltous chloride are clinically similar to those produced by systemic administration of kainic acid and amygdala kindling. These are characterized by staring spells, wet dog shakes, mild convulsive movements, and stereotyped convulsions. ECoG findings demonstrated a unique epileptic burst during the wet dog shakes. Generalized epileptiform discharges were seen during typical seizures. The burst of spikes first occurred in the opposite temporal and frontal regions; and then became generalized. Among the 5 anticonvulsants studied, phenobarbital (30 mg/kg) and nitrazepam (3 mg/kg) completely antagonized the seizures; carbamazepine showed a moderate effect; and phenytoin as well as sodium valproate showed little effect. It is postulated that the seizures induced by cobaltous chloride may originate in the limbic system; and that cobalt ions are responsible for the seizure-inducing action. The mechanism remains to be investigated.
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PMID:Seizures induced by intraventricular microinjection of ionized cobalt in the rat--a new experimental model of epilepsy. 404 34

Much evidence shows that glia regulates the cation and anion content of brain interstitial space. In rats the pH and bicarbonate (HCO3-) concentration of neurons and glia were derived from carbon 14-labeled HCO3- and dimethyloxazolidinedione uptake into brain and cerebrospinal fluid. Acetazolamide increases the total CO2 concentration in neurons and decreases the pH and HCO3- concentration in glia. Inhibition of glial carbonic anhydrase (CA) reduces conversion of neuronally derived CO2 to HCO3-, glial pH is lowered, and neuronal CO2 accumulates. CA therefore has an essential role in regulating pH in neurons, glia, and interstitial fluid. In audiogenic seizure mice, glial CA activity is increased and glial anion transport is reduced. As the mice age, seizure susceptibility, the increased CA activity, and the defect in anion transport disappear concurrently. The enhanced CA activity in the glial cells of these mice is an adaptive mechanism to overcome the defect in anion transport that results from a deficiency of HCO3- -dependent and Na+- and K+ -dependent adenosine triphosphatase. Pentylenetetrazol stimulates neurons in neonatal rats, but after 10 days of age, when glia is present, it too is stimulated and the seizures are attenuated. Cobalt implantation in the cortex of rats also induces a glial response that ameliorates the focal seizures produced by this procedure.
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PMID:Ionic and acid-base regulation of neurons and glia during seizures. 615 Jun 82

Crude mitochondrial synaptosomal (P2) fractions were used to measure L-glutamate 1-decarboxylase (GAD) activity, and crude synaptic membranes were isolated from rat brains and used to determine gamma-aminobutyric acid (GABA) concentration and postsynaptic GABA receptor binding characteristics in rats with cobalt, copper, or glass implanted in right and left cerebral cortices. Copper was employed as a positive metal control because it elicits a morphological profile similar to that of cobalt but is non-epileptogenic. From tissue adjacent to the lesion, GAD activity was assessed by counting trapped 14CO2 liberated from [14C]glutamate and was reduced maximally to 25% of glass controls 7 days following cobalt insult, a period of peak seizure incidence. No reduction in GAD activity was observed 1 or 21 days after cobalt treatment or at any time period in copper-or glass-treated animals. A radioligand [3H]GABA receptor assay was utilized to determine GABA levels, postsynaptic receptor number (Bmax), and the affinity of the postsynaptic receptor for the ligand (KD) in tissue surrounding the lesion. GABA concentration was reduced maximally to 47% of glass controls 7 days following cobalt implantation. Scatchard plot analysis of tissue adjacent to the cobalt lesion revealed a significant increase in apparent receptor density (Bmax) to 200% of glass controls 7 days after bilateraL cobalt implantation (Bmax = 3.97 +/- 0.83 pmol/mg of protein, cobalt versus 1.36 +/- 0.17, glass control). Moreover, at 7 days, no change in kinetic parameters was noted after copper treatment. From days 7 to 21, the density (Bmax) of postsynaptic GABA receptors in cobalt-treated tissue appears to return slowly to glass control values. Results from the present study suggest that degeneration of the GABA pathway in the frontal cortex of the cobalt-epileptic rat occurs and, coupled with the increased Bmax, may represent a "denervation supersensitivity" phenomenon.
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PMID:gamma-Aminobutyric acid concentration, L-glutamate 1-decarboxylase activity, and properties of the gamma-aminobutyric and postsynaptic receptor in cobalt epilepsy in the rat. 627 45

Rats rendered chronically epileptic by bilateral implantation of cobalt into frontal cortices were simultaneously prepared with permanent electrodes for longitudinal recording of the electroencephalogram (EEG) and electromyogram (EMG). Delta-8-tetrahydrocannabinol (delta-8-THC; 10 mg/kg), delta-9-tetrahydrocannabinol (delta-9-THC; 10 mg/kg), cannabidiol (CBD; 60 mg/kg), or polyvinylpyrrolidone (PVP) vehicle (2 ml/kg) was administered IP twice daily from day 7 through 10 after cobalt implantation, at which time generalized seizure activity in non-treated cobalt-epileptic rats was maximal. Relative to PVP-treated controls, CBD did not alter the frequency of appearance of seizures during the course of repeated administration. In contrast, both delta-8-THC and delta-9-THC markedly reduced the incidence of seizures on the first and second days of administration. Interictal spiking during this period, on the other hand, was actually enhanced. On the third and fourth days, tolerance to the effect on seizures was evident, with a return of seizure frequency of THC-treated rats to values not significantly different from those of controls. Unlike the effect on seizures, no tolerance developed to the marked suppression of rapid eye movement (REM) sleep induces by delta-8-THC and delta-9-THC. REM sleep remained reduced in the treated animals during the first 2 days after termination of THC administration. In contrast, REM sleep time was unaffected by repeated administration of CBD. These results suggest that delta-8-THC and delta-9-THC exert their initial anticonvulsant effect by limiting the spread of epileptogenic activity originating from the cobalt focus.
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PMID:Effects of marihuana cannabinoids on seizure activity in cobalt-epileptic rats. 628 Feb 4

The new anticonvulsant drug pargypiranone was studied in different models of experimental epilepsy in cat (penicillin and Premarin cortical focus, cobalt cortical focus, penicillin generalized epilepsy). The drug proved to possess a strong anticonvulsant effect upon focal electroclinical phenomena and a poor effect on penicillin generalized epilepsy. It seems probably that pargypyranone has a valid effect on partial epileptic seizures.
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PMID:[Anticonvulsant action of pargyropyranone in various models of experimental epilepsy in the cat]. 629 88

Transection of the spinal cord of the cat at a thoracic or lumbar level results, after as short a period as 12 days, in a preparation with such altered excitability that repeated natural stimulation of the dermatome just caudal to the transection site will induce, in as short a time as 3 days, seizure discharges. The trigger zone for the seizure spreads to caudal dermatomes when these caudal regions are repeatedly stimulated. The 'typical' T4-T7 seizure is a scratch reflex followed by the tonic-clonic seizure lasting for 20-30 s and ending with a scratch afterdischarge lasting for several minutes. Lower thoracic and upper lumbar seizures consist of tonic-clonic co-contractions of the muscles of the hindlegs, followed by rhythmical stepping movements lasting less than 1 min. Partial dorsal rhizotomy or local Cobalt application to the spinal cord may reduce the threshold for induction of seizure by natural stimulation and local Penicillin application to spinal cord induces seizure discharges similar to those induced by natural stimulation. Retransection of the spinal cord caudally, with elimination of the primary trigger zone, does not abolish the secondarily acquired triggers. The findings suggest that spinal circuits possess the ability to acquire new neuronal patterns of discharge and to transfer them to other more caudal segments.
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PMID:Induction of spinal seizures by natural stimulation in cats. 673 53

Crude brain homogenates and cerebral tissue slices from rats with cobalt metal implanted in right and left cerebral cortices were used to examine high- and low-affinity GABA transport. High-affinity GABA transport was maximally reduced to 34% of controls 7 days after cobalt implantation, a time that coincides with peak seizure activity in this model. Kinetic analysis of high-affinity GABA transport, using brain homogenates, revealed a significant change in Vmax 7 days after cobalt implantation. (Vmax = 446.4 +/- 26.2 pmol/mg prot./min, cobalt, versus 787.8 +/- 67.3, control). An analysis of the low-affinity system revealed no depression of Km or Vmax parameters. Administration of valproic acid at a concentration as high as 1 mM in vitro or a dose of 300 mg/kg in vivo had no effect on high- or low-affinity GABA transport. The results obtained from cobalt-treated rats provide additional evidence for an involvement of GABA in experimental epilepsy.
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PMID:Studies on gamma-aminobutyric acid transport in cobalt experimental epilepsy in the rat. 678 93

The topohistochemistry of gamma-aminobutyric acid (GABA) was studied in the hippocampus of rats with epileptiform activity provoked by cortical implantation of cobalt-agar pellets and in control rats with implanted agar-pellets. Using the GABA specific fluorochroming procedure of Wolman (1971) a distinct decrease of GABA fluorescence was found especially in the pyramidal and granular layer, but only in the animals with a typical epileptiform activity of the EEG. The results support the hypothesis that there is a lack of GABAergic inhibition in epileptic individuals, but the anticonvulsive effect of GABA depends on structural and functional relations in the specific type of seizure.
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PMID:A loss of GABAergic hippocampus innervation in rats with cobalt-induced epilepsy demonstrated by Wolman's fluorescence method. 680 24

In former investigations on human focal epilepsy and on experimental epilepsy by cobalt implantation, the authors have demonstrated the signaletic importance of "activated astrocytes": cortical astrocytes endowed with a modified metabolism and an accelerated turnover. The present study concerns the results of the intra-amygdaloid injections of kainic acid, a strong excitatory and neurotoxic amino acid. Injections in semi-chronic conditions in the rat lead to electrical and motor seizures and to the production of activated astrocytes not only in regions that might trigger off epileptic seizures (cerebral cortex, amygdala, possibly hippocampus), but also in the neostriatum. Stimulation of this last region results in a Huntington chorea-like syndrome. Thus, the importance of activated astrocytes must be extended to include other conditions of intense hyperactivity of neurons than epilepsy.
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PMID:[Histochemical study of central nervous system lesions in experimental epilepsy caused by kainic acid]. 732 58

The effects of alpha-guanidinoglutaric acid (GGA), the levels of which were increased in the cobalt-induced epileptic focus tissue in the cerebral cortex of cats, on brain nitric oxide synthase (NOS) activity were observed. GGA inhibited NOS activity in a linear mixed manner (Ki = 2.69 microM) and was as effective as NG-monomethyl-L-arginine (MeArg; Ki = 3.51 microM), a well-known NOS inhibitor. Although MeArg was synthesized by substituting the guanidino nitrogen of L-arginine (Arg), GGA was a non-guanidino nitrogen-substituted guanidino compound. On the other hand, Arg, which is an endogenous NOS substrate, elevates the threshold of seizures induced by GGA. There is evidence that GGA is an endogenous, potent, and non-guanidino nitrogen-substituted NOS inhibitor and that suppression of nitric oxide biosynthesis may be involved in GGA-induced convulsions. Therefore, GGA may be a useful tool in elucidating the chemical nature of NOS and the physiological function of nitric oxide.
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PMID:alpha-Guanidinoglutaric acid, an endogenous convulsant, as a novel nitric oxide synthase inhibitor. 752 94


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