Pharmacodynamics of the anticonvulsant effect of oxazepam in aging BN/BiRij rats

Stijnen, A. M.; Postel-Westra, Ineke; Langemeijer, M. W. E.; Hoogerkamp, A.; Voskuyl, Rob A.; Bezooijen, C.F.A. van; Danhof, Meindert

doi:10.1111/j.1476-5381.1992.tb14481.x

Cited by 10 publications

(2 citation statements)

References 39 publications

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“…Using electrical stimulation to induce acute seizures, there was no observed effect of age on the seizure threshold with direct cortical stimulation in BN/BiRij rats. Very old animals (35 months) were more sensitive to the anticonvulsant effect of oxazepam and did not display the proconvulsant effects at higher doses that were seen in younger animals (33). In another study, using Wistar rats, increased blood-brain barrier permeability to macromolecules was seen in 24-month-old animals after 10 electroconvulsive shocks (but not after one), suggest-ing that the older animals are more susceptible to injury caused by repeated seizures (34).…”

Section: Models Of Acute Seizures In Aged Ratsmentioning

confidence: 96%

Aging Models of Acute Seizures and Epilepsy

Kelly¹

2010

Epilepsy Curr

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Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute Models of Acute Seizures in Aged MiceIn aged animals, the most commonly used models employ electrical stimulation or a convulsant agent, such as kainic acid, pilocarpine, or pentylenetetrazol, to induce acute seizures. Depending on the model and the animal strain used, the results of studies of acute seizures in aged animals have variably demonstrated increased or decreased seizure susceptibility associated with advanced age. Early studies, using the BDF1 mouse strain (a cross between female C57BL/6 and male DBA/2 mice), ex- plored the effect of aging on acute seizure susceptibility and demonstrated that the threshold for the tonic extensor component of maximal electroshock seizures increased with age (up to 30 months) (1). Similarly, the minimal effective concentration of pentylenetetrazol needed to induce maximal seizure activity increased in 24-month-old compared to 6-month-old animals (2), as did the sensitivity to the anticonvulsant effects of oxazepam (3) and phenobarbital in the same model (4). These studies suggested that aged BDF1 mice required increased levels of electrical or chemical stimulation to generate acute seizures, whereas decreased concentrations of anticonvulsants active at the GABA A receptor were required to mitigate pentylenetetrazol-induced maximal seizure activity.Except for early studies of BDF1 mice, which showed equivalent effects in both male and female animals (1-3), relatively few studies have assessed gender-based differences in seizure susceptibility and/or neurodegeneration in mice. A study of seizure susceptibility in adult and aged animals of the inbred CBA strain demonstrated that 3-month-old males were distinctly more prone to seizures induced by the GABA A receptor antagonists, bicuculline and picrotoxin, compared to age-matched females; picrotoxin-induced seizure latencies were also decreased in the male animal (5). However, there was no gender-based difference in sensitivity to picrotoxin in 24-month-old animals. Comparing adult and aged male and female C57BL/6J mice following kainic acid treatment, aged female mice demonstrated more severe seizure activity, prominent hippocampal injury, and increased astrocyte proliferation (6). In studies not based on gender but using the same C57BL/6J strain, acute seizures were induced by a single electroconvulsive shock, followed by assessment of c-fos expression in different brain regions of varying age groups. All ages exhibited a transient increase in c-fos immunoreactivity, but in aged animals, the response was significantly less robust (7). Following a single dose of kainic acid, aged C57BL/6J mice were more sensitive to its pathological effects compared to adult animals, especially with regard to neuroinflammatory changes, as measured by markers of reactive gliosis (8). Comparing young adult, mid-aged, and aged C57BL/6J mice to similarly...

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Section: Models Of Acute Seizures In Aged Ratsmentioning

confidence: 96%

Aging Models of Acute Seizures and Epilepsy

Kelly¹

2010

Epilepsy Curr

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“…Compared to younger, aged animals were more susceptible to induced seizures, typically more severe and leading to a greater degree of hippocampal degeneration [15]. Moreover, aged mice exhibited a lower threshold for seizures when different drugs were used to induce them (kainic acid, pilocarpine, nicotine) and were more sensitive to the GABAergic (gamma-aminobutyric acid) anticonvulsant action of benzodiazepines like oxazepam [17,18]. Investigation in specific mice models demonstrated a general reduction of transcriptional responses for several proteins following induced seizures in the aged brain.…”

Section: Discussionmentioning

confidence: 99%

Status Epilepticus in an Internal Medicine Ward: Different Patients Therefore Distinct Approaches

Trindade¹,

Teixeira²,

Serôdio³

et al. 2023

Cureus

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BackgroundStatus epilepticus (SE) is a medical condition that bestows substantial morbidity and mortality. Literature is scarce regarding SE in elderly patients, particularly in the context of internal medicine wards. AimTo characterize SE patients admitted to an internal medicine ward, identify potential outcome predictors and differences between young and elderly, as well as convulsive (CSE) and non-convulsive SE (NCSE) patients. MethodsWe enrolled 135 consecutive patients in an observational, retrospective cohort study. We established elderly patients as more than 64 years old and defined worse prognosis as a modified Rankin Scale (mRS)>4. ResultsThe SE population was 73% elderly, and 75% presented with NCSE, mainly metabolic, idiopathic, or vascular SE. The intra-hospital mortality was 51%, and 62% had an mRS>4 at discharge. NCSE and electroencephalogram (EEG) with paroxysmal activity at discharge were predictive of a worse prognosis. Elderly patients had increased disability at admission, most had NCSE (81%), and the SE etiology differed with more idiopathic and vascular causes. In the elderly, mortality was increased, as was the number of patients with mRS>4 at discharge. NCSE patients had the more neurodegenerative disease (30%) and presented predominantly with vascular and anoxic causes. Morbidity and mortality were also increased in the NCSE group. There was no difference in the antiepileptic drugs used or in the percentage of patients achieving an EEG with no paroxysmal activity between the subpopulations. ConclusionSE in elderly patients should be addressed distinctly. Current approaches based on the strategies used for standard CSE have shown little or no efficacy overall.

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