Abstracts

Rationale: Hypoxic-ischemic (HI) brain injury is the most common cause of seizures during the neonatal period. Quantitative electrographic analyses in animal models are important for preclinical studies to develop new therapies for neonatal seizures. Here, a custom-built, miniature telemetry device was used to analyze acute seizures during either HI or hypoxia-alone treatment in neonatal rats. The hypothesis was that both of these treatments cause electrographic seizures during the acute hypoxic period, but only animals in the HI group develop cortical lesions with substantive neuronal damage. Methods: The telemetry device was implanted on rat pups at postnatal day 6-7. Animals were allowed to recover for 24 h, and were then treated with HI or hypoxia alone. In the HI group, the left common carotid artery was cauterized before hypoxia. The pups were allowed to recover for 2 h with the dam, and were then treated for 2 h with 8% oxygen and 92% nitrogen (i.e., hypoxia) at 37 C. Results: After carotid occlusion but before hypoxia, electrographic activity appeared normal in both the HI and hypoxia-alone groups. Animals (n=6 per group) in either the HI or hypoxia groups exhibited at least three distinct, abnormal forms of electrographic activity during hypoxia, including robust electrographic seizures of various durations. The average number of seizure events was similar across the groups (15.2 ( 2.3) after HI and 16 ( 3.4) after hypoxia alone during the 2 h exposure). Histopathological analyses revealed that only animals with HI developed cortical lesions. Preliminary analyses showed few if any Fluro-Jade stained neurons (a marker for degenerating neurons) after the hypoxia-induced seizures, thus indicating that hypoxia-induced seizures (i.e., without ischemia) do not induce substantive brain damage. Conclusions: Recent evidence (Kadam et al., 2010 J Neurosci 30:404) suggests that HI-treated neonatal rats without infarcts do not develop epilepsy. Here, both HI and hypoxia, induced intense seizures in immature rat pups. When combined with previous work (Kadam et al.,2010), these data suggest that neonatal seizures per se do not cause substantive brain damage, and hypoxia-induced neonatal seizures alone (i.e., without brain lesions) do not lead to epilepsy. The ability to record electrographic seizure activity during the neonatal period should enable quantitative analyses of seizures during the neonatal period to determine if they exacerbate other forms brain injury, and should also promote testing of novel therapeutic approaches for neonatal seizures during the early phases of perinatal stroke.