Hippocampal excitability is increased in aged mice.

Aging is known to be associated with a high risk of developing seizure disorders. Currently, the mechanisms underlying this increased seizure susceptibility are not fully understood. Several previous studies have shown a loss of subgroups of GABAergic inhibitory interneurons in the hippocampus of aged rodents, yet the network excitability intrinsic to the aged hippocampus remains to be elucidated. The aim of this study is to examine age-dependent changes of hippocampal network activities in young adult (3-5 months), aging (16-18 months), and aged (24-28 months) mice. We conducted intracranial electroencephalographic (EEG) recordings in free-moving animals and extracellular recordings in hippocampal slices in vitro. EEG recordings revealed frequent spikes in aging and aged mice but only occasionally in young adults. These EEG spikes were suppressed following diazepam administration. Spontaneous field potentials with large amplitudes were frequently observed in hippocampal slices of aged mice but rarely in slices from young adults. These spontaneous field potentials originated from the CA3 area and their generation was dependent upon the excitatory glutamatergic activity. We therefore postulate that hippocampal network excitability is increased in aged mice and that such hyperactivity may be relevant to the increased seizure susceptibility observed in aged subjects.

Early suppression of intracranial EEG signals predicts ischemic outcome in adult mice following hypoxia-ischemia.

The objective of this study is to determine whether early alterations in intracranial EEG activity predict overall outcome in non-anesthetized adult mice following hypoxia-ischemia (HI). Adult C57BL/6 mice received surgical implantation of bilateral intracranial EEG electrodes in the hippocampus and cerebral cortex. Animals were subjected to a hypoxic-ischemic (HI) episode consisting of permanent occlusion of the right common carotid artery and subsequent systemic hypoxia (8% O(2) for 30 min). EEG activities were sorted based on the observance of motor seizures, poor physical outcome, brain injury, and mortality. EEG signals were quantified as amplitude, variance, and root mean square, and early alterations in these parameters were compared. Animals with poor-HI outcome exhibited longer and more profound suppression of EEG signals in the hippocampus ipsilateral to the carotid artery occlusion during HI. Of the parameters chosen to quantify EEG activity, root mean square demonstrated the greatest sensitivity in predicting subsequent outcome. Thus, ipsilateral hippocampal EEG signals are a reliable early marker for assessing HI outcome in adult mice, and further characterization of ischemic EEG signals may aid in the development of novel quantitative variables for use in animal models of experimental cerebral ischemia.

Acute postischemic seizures are associated with increased mortality and brain damage in adult mice.

Postischemic seizures are associated with worsened outcome following stroke, but the underlying pathophysiology is poorly understood. Here we examined acute seizures in adult mice following hypoxia-ischemia (HI) via combined behavioral, electrophysiological, and histological assessments. C57BL/6 mice aged 4-9 months received a permanent occlusion of the right common carotid artery and then underwent a systemic hypoxic episode. Generalized motor seizures were observed within 72 h following HI. These seizures occurred nearly exclusively in animals with extensive brain injury in the hemisphere ipsilateral to the carotid occlusion, but their generation was not associated with electroencephalographic discharges in bilateral hippocampal and neocortical recordings. Animals exhibiting these seizures had a high rate of mortality, and post-HI treatments with diazepam and phenytoin greatly suppressed these behavioral seizures and improved post-HI animal survival. Based on these data, we conclude that these seizures are a consequence of HI brain injury, contribute to worsened outcome following HI, and that they originate from deep subcortical structures.