Development and Persistence of Kindled Seizures After Repeated Injections of Pentylenetetrazol in Rats and Guinea Pigs

Diehl, Rachel; Smiałowski, A; Gotwo, T.

doi:10.1111/j.1528-1157.1984.tb03452.x

Cited by 61 publications

(15 citation statements)

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“…The repeated injections of such a subconvulsant dose during the five experiments should have produced a progressive sensitization to the effects of PTZ in the animals, which became kindled (46). It has been shown that doses ineffective after the first injection induce tonic seizures after 20 injections (47) and that kindling effect is proportional to the dose of PTZ (48). The decrease of crisis latency and the increase of clonus duration among the control experiments show that kindling increased sensitivity to PTZ convulsant effects.…”

Section: Discussionmentioning

confidence: 91%

Characterization of α‐casozepine, a tryptic peptide from bovine α_s1‐casein with benzodiazepine‐like activity

et al. 2001

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SPECIFIC AIMSAccording to folk wisdom, milk intake improves sleeping or has a calming role, a belief supported by some scientific studies. As caseins contain peptides with physiological roles, we hypothesized that one of their peptides can carry this anxiolytic activity. In this study, ␣ s1 -casein tryptic hydrolysate (␣ s1 -CnTH) was tested in vitro on benzodiazepine (BDZ) receptors and checked in vivo for its anticonvulsant and anxiolytic effects in the rat. PRINCIPAL FINDINGS ␣ s1 -CnTH inhibits pentylenetetrazole (PTZ) -induced seizures in Wistar ratBovine ␣ s1 -CnTH was injected intraperitoneally (i.p.) in a Wistar rat 30 min before an i.p. injection of 60 mg/kg of PTZ to evaluate anticonvulsant activity. Crisis severity parameters, crisis latency, and clonus duration were determined after 45 min observation of behavior. The i.p. injection of 1 mg/kg of ␣ s1 -CnTH reduced crisis severity (PϽ0.02). Other parameters were not significantly different from the control. The i.p. injection of 3 mg/kg of ␣ s1 -CnTH increased crisis latency (PϽ0.005), decreased crisis severity (PϽ0.002), and decreased clonus duration (PϽ0.005) of PTZ-induced seizures. The anticonvulsant action of the ␣ s1 -CnTH was underestimated because of a sensitization of animals to PTZ during successive experiments. ␣ s1 -CnTH displays an anxiolytic activity in the elevated plus maze paradigmElevated plus maze test was used to evaluate the anxiolytic effect of the ␣ s1 -CnTH. Diazepam (1 mg/kg) and ␣ s1 -CnTH (3 mg/kg) enhanced (PϽ0.02) the percentage of entries in the open arms whereas general activity, represented by entries in closed arms, was not modified (Fig. 1). ␣ s1 -CnTH displays an anxiolytic activity in the conditioned defensive burying (CDB) experimentWhen a rat is shocked once through an electrical probe mounted on a wall of a test cage, it returns to the probe and buries it with bedding material from the floor of the cage. This CDB response is reduced by anxiolytic drugs. Some behavioral sequences such as exploratory approaches to the probe and escape movements from the probe are needed to differentiate agonists from partial inverse agonists. Similar to diazepam, the ␣ s1 -CnTH, administrated at 3 mg/kg i.p., decreased the duration of probe burying (PϽ0.005) (Fig. 2). The ratio of the retreats to the approaches decreased in rats treated with ␣ s1 -CnTH or diazepam. The CDB paradigm indicates that the ␣ s1 -CnTH exerts an anxiolytic activity over rats. A peptide (␣-casozepine) of the ␣ s1 -CnTH binds on the BDZ site of the GABA A receptorAffinity for the BDZ site of the GABA A receptor from bovine cerebral cortex membranes was measured in competition with [methyl-3 H]-flunitrazepam. ␣ s1 -CnTH competed with the radioligand for binding on the BDZ site of the GABA A receptor with an IC 50 of 72 1 To read the full text of this article, go to http://www. fasebj.org/cgi/doi/10.1096/fj.00 -0685fje; to cite this article, use FASEB J.

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Section: Discussionmentioning

confidence: 91%

Characterization of α‐casozepine, a tryptic peptide from bovine α_s1‐casein with benzodiazepine‐like activity

et al. 2001

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“…Calibration scale is 1 mm for all panels. Epilepsia ILAE epilepsy/seizure features in these models were cursorily described (Diehl et al, 1984;Popova et al, 2008). Our method induced acute nonconvulsive SE with a very high efficiency, since in only two animals KA injection failed to be effective.…”

Section: Discussionmentioning

confidence: 96%

“…Our study demonstrates that neuropathologic and electroclinical features representative of human mTLE can be reproduced in the guinea pig after local, unilateral injection of KA in one dorsal hippocampus. Attempts to develop a chronic epilepsy model in this animal species were few and epilepsy/seizure features in these models were cursorily described (Diehl et al., 1984; Popova et al., 2008). Our method induced acute nonconvulsive SE with a very high efficiency, since in only two animals KA injection failed to be effective.…”

Section: Discussionmentioning

confidence: 99%

A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid

et al. 2012

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SUMMARYPurpose: Models of temporal lobe epilepsy are commonly utilized to study focal epileptogenesis and ictogenesis. The criteria that define animal models representative of human mesial temporal lobe may vary in different laboratories. We describe herein a focal epilepsy model of mesial temporal (hippocampal) origin that relies on the analysis of interictal and ictal electroencephalography (EEG) patterns and on their correlation with seizure symptoms and neuropathologic findings. The study is based on guinea pigs, a species seldom utilized to develop chronic epilepsy models. Methods: Young adult guinea pigs were bilaterally implanted under isoflurane anesthesia with epidural electrodes over somatosensory cortex and depth electrodes in CA1 hippocampal region. A stainless steel guide cannula was positioned unilaterally in the right dorsal hippocampus to inject 1 ll of 0.9% NaCl solution containing 1 lg kainic acid (KA). One week after surgery, continuous 24 h/day video-EEG monitoring was performed 48 h before and every other week after KA injection, for no <1 month. EEG data were recorded wide-band at 2 kHz. After video-EEG monitoring, brains were analyzed for thionine and Timm staining and glial fibrillary acid protein (GFAP) immunostaining. Key Findings: Unilateral injection of KA in dorsal hippocampus of guinea pigs induces an acute nonconvulsive status epilepticus (SE) that terminates within 24 h (n = 22). Chronic seizures with very mild motor signs (undetectable without EEG monitoring) and highly variable recurrence patterns appear in 45.5% (10 of 22) KAtreated animals, with variable delays from the initial SE. In these animals interictal events, CA1 cell loss, gliosis, and altered Timm staining pattern were observed. The induction of a chronic condition did not correlate with the duration of the nonconvulsive acute SE, but correlated with the extension and quality of neuropathologic damage. Significance: We demonstrate that a model of hippocampal (mesial temporal lobe) epilepsy can be developed in the guinea pig by intrahippocampal injection of KA. Seizure events in this model show little behavioral signs and may be overlooked without extensive video-EEG monitoring. The establishment of a chronic epileptic condition correlates with the extension of the hippocampal damage (mainly cell loss and gliosis) and not with the intensity of the initial SE.

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“…Seizures were induced in IRs and ARs individually with lithium (3 mEq/kg) followed by pilocarpine injected intraperitoneally (40 mg/kg) 18-20 h later. According to Smialowski's six category classification of seizures [11], rats with IV or V class seizures of 1-h duration were admitted. Fifteen minutes after the onset of the seizure, rats were injected intraperitoneally with atropine (1 mg/kg, He Feng Tragacanth Company, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Expression of AMPA receptor subunits in hippocampus after status convulsion

Jiang

Chen

et al. 2012

Childs Nerv Syst

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Development and Persistence of Kindled Seizures After Repeated Injections of Pentylenetetrazol in Rats and Guinea Pigs

Cited by 61 publications

References 16 publications

Characterization of α‐casozepine, a tryptic peptide from bovine α_s1‐casein with benzodiazepine‐like activity

Characterization of α‐casozepine, a tryptic peptide from bovine α_s1‐casein with benzodiazepine‐like activity

A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid

Expression of AMPA receptor subunits in hippocampus after status convulsion

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Development and Persistence of Kindled Seizures After Repeated Injections of Pentylenetetrazol in Rats and Guinea Pigs

Cited by 61 publications

References 16 publications

Characterization of α‐casozepine, a tryptic peptide from bovine αs1‐casein with benzodiazepine‐like activity

Characterization of α‐casozepine, a tryptic peptide from bovine αs1‐casein with benzodiazepine‐like activity

A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid

Expression of AMPA receptor subunits in hippocampus after status convulsion

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Characterization of α‐casozepine, a tryptic peptide from bovine α_s1‐casein with benzodiazepine‐like activity

Characterization of α‐casozepine, a tryptic peptide from bovine α_s1‐casein with benzodiazepine‐like activity