Acute and chronic increases in excitability in rat hippocampal slices after perinatal hypoxia in vivo. F. E. Jensen, C.Wang, C.E. Stafstrom, Z. Liu, C. Geary, and M.C. Stevens. Department of Neurology, Children's Hospital, and Program in Neuroscience, Harvard Medical School, Boston MA, and Division of Pediatric Neurology, New England Medical Center, Tufts University School of Medicine, Boston, MA.
APStracts 4:0247N, 1997.
ABSTRACT
We have previously shown that hypoxia induces both acute and chronic epileptogenic effects which are age-dependent. Global hypoxia (3-4%O2) induces seizure activity in the developing brain (postnatal day P10-12) but not at younger or older ages (Jensen et al. 1991a). Adult rats with prior seizures induced by hypoxia at P10 show increased seizure susceptibility to chemical convulsants compared to controls (Jensen et al. 1991b; Jensen et al. 1992). In the present study, we tested the hypothesis that acute and chronic epileptogenic effects of hypoxia are demonstrable in hippocampus both in vivo and in vitro. Depth electrode recordings confirmed the presence of ictal activity within hippocampus in P10 rats during global hypoxia. Hippocampal slices prepared from P10 pups sacrificed at 10 min after recovery from hypoxia showed evidence of increased excitability. Extracellular field recordings revealed that the amplitude and duration of long term potentiation (LTP) was significantly increased in area CA1 of hippocampal slices removed from hypoxic pups. In addition, extracellular recordings within areas CA1 and CA3 showed significantly longer afterdischarge durations in response to kindling stimuli in slices from hypoxic pups compared to controls. To evaluate whether there were also long term changes in hippocampal excitability, hippocampal slices were prepared from adult rats which underwent hypoxia at P10 and compared with slices from adult litter mate controls. A Mg2+-free medium was superfused to induce epileptiform activity within the slices. Extracellular recordings from s. pyramidale of area CA1 showed that Mg2+-free media induced significantly more frequent ictal discharges in slices from previously hypoxic rats compared to controls. These results provide evidence that the naturally occurring stimulus of hypoxia can result in both acute and chronic changes in the excitability of the CA1 neuronal network. These results parallel our previous in vivo studies demonstrating that global hypoxia acutely increases excitability in the immature brain, and that hypoxia during the age window around P10 results in long lasting increases in seizure susceptibility within hippocampus. Our results suggest that the age-dependent epileptogenic effects of hypoxia are in part mediated by a direct and permanent effect on neuronal excitability within hippocampal neuronal networks. 

Received 11 April 1997; accepted in final form 9 September 1997.
APS Manuscript Number J296-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997