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Continuous electroencephalographic monitoring with radio-telemetry in a rat model of perinatal hypoxia-ischemia reveals progressive post-stroke epilepsy.

ABSTRACT: The development of acquired epilepsy after a perinatal hypoxic-ischemic (HI) insult was investigated in rats. After unilateral carotid ligation with hypoxia on postnatal day 7, cortical electroencephalographic and behavioral seizures were recorded with continuous radio-telemetry and video. Chronic recordings were obtained between 2 and 12 months of age in freely behaving HI-treated and sham control rats. The hypotheses were that the acquired epilepsy is directly associated with an ischemic infarct (i.e., no lesion, no epilepsy), and the resultant epilepsy is temporally progressive. Every HI-treated rat with a cerebral infarct developed spontaneous epileptiform discharges and recurrent seizures (100%); in contrast, no spontaneous epileptiform discharges or seizures were detected with continuous monitoring in the HI-treated rats without infarcts. The initial seizures at 2 months generally showed focal onset and were nonconvulsive. Subsequent seizures had focal onsets that propagated to the homotopic contralateral cortex and were nonconvulsive or partial; later seizures often appeared to have bilateral onset and were convulsive. Spontaneous epileptiform discharges were initially lateralized to ipsilateral neocortex but became bilateral over time. The severity and frequency of the spontaneous behavioral and electrographic seizures progressively increased over time. In every epileptic rat, seizures occurred in distinct clusters with seizure-free periods as long as a few weeks. The progressive increase in seizure frequency over time was associated with increases in cluster frequency and seizures within each cluster. Thus, prolonged, continuous seizure monitoring directly demonstrated that the acquired epilepsy after perinatal HI was progressive with seizure clusters and was consistently associated with a cerebral infarct.

SUBMITTER: Kadam SD

PROVIDER: S-EPMC2903060 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Continuous electroencephalographic monitoring with radio-telemetry in a rat model of perinatal hypoxia-ischemia reveals progressive post-stroke epilepsy.

Kadam Shilpa D SD White Andrew M AM Staley Kevin J KJ Dudek F Edward FE

The Journal of neuroscience : the official journal of the Society for Neuroscience 20100101 1

The development of acquired epilepsy after a perinatal hypoxic-ischemic (HI) insult was investigated in rats. After unilateral carotid ligation with hypoxia on postnatal day 7, cortical electroencephalographic and behavioral seizures were recorded with continuous radio-telemetry and video. Chronic recordings were obtained between 2 and 12 months of age in freely behaving HI-treated and sham control rats. The hypotheses were that the acquired epilepsy is directly associated with an ischemic infar ...[more]

PMID: 20053921

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Project description:Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus encephalitis in animals relies on traditional physiological biomarkers and behavioral/neurological observations by veterinary staff; quantitative measurements such as electroencephalography (EEG) and intracranial pressure (ICP) can recapitulate underlying encephalitic processes. We detail a telemetry implantation method suitable for continuous monitoring of both EEG and ICP in awake macaques, as well as methods for collection and analysis of such data. We sought to evaluate whether changes in EEG/ICP suggestive of CNS penetration by virus would be seen after aerosol exposure of naïve macaques to VEEV IC INH9813 or EEEV V105 strains compared to mock-infection in a cohort of twelve adult cynomolgus macaques. Data collection ran continuously from at least four days preceding aerosol exposure and up to 50 days thereafter. EEG signals were processed into frequency spectrum bands (delta: [0.4 - 4Hz); theta: [4 - 8Hz); alpha: [8-12Hz); beta: [12-30] Hz) and assessed for viral encephalitis-associated changes against robust background circadian variation while ICP data was assessed for signal fidelity, circadian variability, and for meaningful differences during encephalitis. Results indicated differences in delta, alpha, and beta band magnitude in infected macaques, disrupted circadian rhythm, and proportional increases in ICP in response to alphavirus infection. This novel enhancement of the cynomolgus macaque model offers utility for timely determination of onset, severity, and resolution of encephalitic disease and for the evaluation of vaccine and therapeutic candidates.

Dataset Information

Continuous electroencephalographic monitoring with radio-telemetry in a rat model of perinatal hypoxia-ischemia reveals progressive post-stroke epilepsy.

Publications

Continuous electroencephalographic monitoring with radio-telemetry in a rat model of perinatal hypoxia-ischemia reveals progressive post-stroke epilepsy.

Similar Datasets

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