Kainic acid induced limbic seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates

Lothman, Eric W.; Collins, Ruth

doi:10.1016/0006-8993(81)91308-1

Cited by 660 publications

(271 citation statements)

References 52 publications

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“…All animals treated with KA, regardless of whether they also received memantine, displayed behavioral automatisms of the type characteristically observed in KAtreated rats (Lothman and Collins, 1981). In the 30 -45 min posttreatment period, they showed preconvulsive behaviors consisting primarily of staring spells and wetdog shakes.…”

Section: Neuroprotective Effects Of Memantinementioning

confidence: 79%

Low Doses of Memantine Disrupt Memory in Adult Rats

Creeley¹,

Wozniak²,

Labruyere³

et al. 2006

J. Neurosci.

120

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Memantine, a drug recently approved for treatment of Alzheimer's disease, has been characterized as a unique NMDA antagonist that confers protection against excitotoxic neurodegeneration without the serious side effects that other NMDA antagonists are known to cause. In the present study, we determined what dose of memantine is required to protect the adult rat brain against an NMDA receptormediated excitotoxic process and then tested that dose and a range of lower doses to determine whether the drug in this dose range is associated with significant side effects. Consistent with previous research, we found that memantine confers a neuroprotective effect beginning at an intraperitoneal dose of 20 mg/kg, a dose that we found, contrary to previous reports, produces locomotor disturbances severe enough to preclude testing for learning and memory effects. We then determined that, at intraperitoneal doses of 10 and 5 mg/kg, memantine disrupts both memory and locomotor behaviors. Rats treated with these doses performed at control-like levels in learning a hole-board task but were significantly impaired in demonstrating what they had learned when tested 24 h later. This impairment of memory retention was not state dependent in that it was demonstrable regardless of whether the rats were or were not exposed to memantine on the day of retention testing. We conclude that, in the adult rat, memantine behaves like other NMDA antagonists in that it is neuroprotective only at doses that produce intolerable side effects, including memory impairment.

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Section: Neuroprotective Effects Of Memantinementioning

confidence: 79%

Low Doses of Memantine Disrupt Memory in Adult Rats

Creeley¹,

Wozniak²,

Labruyere³

et al. 2006

J. Neurosci.

120

View full text Add to dashboard Cite

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“…Systemic administration of KA induces typical limbic seizures whose behavioral, electroencephalographic, thermal, systemic, meta bolic, and cerebrovascular characteristics in awake rats have been extensively described previously (Ben Ari et aI., 1981; Lothman and Collins, 1981;Pinard et aI., 1984Pinard et aI., , 1987. The aim of the present study was to determine the influence of a NOS blocker, L-NAME, on the cere brovascular, thermal, systemic, electrographic, and behavioral effects of KA-induced seizures and thus to assess whether NO is mostly beneficial or mostly deleterious in prolonged limbic seizures.…”

mentioning

confidence: 71%

Blockade of Nitric Oxide Synthesis Inhibits Hippocampal Hyperemia in Kainic Acid-Induced Seizures

Rigaud-Monnet

Pinard

Borredon

et al. 1994

J Cereb Blood Flow Metab

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Summary:We investigated whether the nitric oxide (NO) synthase inhibitor �-nitro-L-arginine methyl ester (L NAME) affects the cerebrovascular changes occurring in seizures induced by kainic acid (KA) in awake, sponta neously breathing rats. Blood flow and tissue P02 and Pco2 were continuously and simultaneously measured by mass spectrometry from a cannula chronically implanted into the dorsal hippocampus. L-NAME (20 mg/kg; n = 8) or saline (n = 9) was administered i.p. 30 min prior to i.p. KA (10 mg/kg) injection. L-NAME significantly de creased hippocampal blood flow and P02 and increased mean arterial blood pressure (MABP). In L-NAME treated rats, seizure activity occurred about 10 min sooner than in control rats, and status epilepticus was inevitably followed by a flat electroencephalogram and In recent years, a growing body of evidence has suggested that NO contributes to the regulation of blood vessel tone and acts as a peripheral and cen tral neuronal messenger (Garthwaite et aI., 1988).Received July 30, 1993; final revision received January 12, 1994; accepted January 24, 1994. Address correspondence and reprint requests to Dr. E. Pinard, CNRS VA 641, 10, Avenue de Verdun, 75010 Paris, France.Abbreviations used: ANOV A, analysis of variance; CVR, ce rebrovascular resistance; DPC, deep piriform cortex; ECoG, electrocorticogram; HBF, hippocampal blood flow; KA, kainic acid; L-NAME, �-nitro-L-arginine methylester; MABP, mean arterial blood pressure; NO, nitric oxide; NOS, nitric oxide syn thase; RT, rectal temperature; WDS, wet-dog shakes. 581sudden death. In contrast, control rats survived KA induced seizures. Hippocampal blood flow was signifi cantly less elevated during the seizures in L-NAME treated rats than in control rats (maximal levels, 170 and 450%, respectively, of baseline values), though MABP remained significantly higher. Hippocampal P02 was sig nificantly decreased at all times after KA injection in L-NAME-treated rats, whereas it remained at or above normoxic levels in control rats. The present results show that L-NAME markedly attenuates the hippocampal blood flow and tissue P02 changes in response to en hanced metabolic activity due to limbic seizures and sug gest that NO is of major importance in cerebral blood flow control during KA-induced seizures.

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“…Indeed, thalamic stimulation yields short-latency excitatory responses in the entorhinal cortex and hippocampus (30)(31)(32). Moreover, in a number of studies using different models for limbic SE, the 2-deoxyglucose mapping of metabolic activity has underscored clearly the involvement of the midline thalamic nuclei (33)(34)(35)(36). Second, we did not analyze BBB breakdown before 2 h or between 2 and 6 h after the onset of SE.…”

Section: Figmentioning

confidence: 99%

Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats

et al. 2002

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Summary:Purpose: In temporal lobe epilepsy, it remains to be clarified whether hippocampal sclerosis is the cause or the consequence of epilepsy. We studied the temporal evolution of the lesions in the lithium-pilocarpine model of epilepsy in the rat with magnetic resonance imaging (MRI) to determine the progressive morphologic changes occurring before the appearance of chronic epilepsy.Methods: MRI was performed on an MR scanner operating at 4.7 T. We followed the evolution of lesions using T 2 -and T 1 -weighted sequences before and after the injection of gadolinium from 2 h to 9 weeks.Results: At 2 h after status epilepticus (SE), a blood-brain barrier breakdown could be observed only in the thalamus; it had disappeared by 6 h. At 24 h after SE, edema was present in the amygdala and the piriform and entorhinal cortices together with extensive neuronal loss; it disappeared progressively over a 5-day period. During the chronic phase, a cortical signal reappeared in all animals; this signal corresponded to gliosis, which appeared on glial fibrillary acidic protein (GFAP) immunohistochemically stained sections as hypertrophic astrocytes with thickened processes. In the hippocampus, the correlation between histopathology and T 2 -weighted signal underscored the progressive constitution of atrophy and sclerosis, starting 2 days after SE.Conclusions: These data show the reactivity of the cortex that characterizes the initial step leading to the development of epilepsy and the late gliosis that could result from the spontaneous seizures. Moreover, it appears that hippocampal sclerosis progressively worsened and could be both the cause and the consequence of epileptic activity.

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Kainic acid induced limbic seizures: metabolic, behavioral, electroencephalographic and neuropathological correlates

Cited by 660 publications

References 52 publications

Low Doses of Memantine Disrupt Memory in Adult Rats

Low Doses of Memantine Disrupt Memory in Adult Rats

Blockade of Nitric Oxide Synthesis Inhibits Hippocampal Hyperemia in Kainic Acid-Induced Seizures

Magnetic Resonance Imaging in the Study of the Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Adult Rats

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