HYPOXIA-INDUCED DYSFUNCTION IN DEVELOPING RAT NEOCORTEX

Neocortical slices from young [postnatal day (P) 5-8], juvenile (P14-1 8), and adult (>P28) rats were exposed to long periods of hypoxia. Fie ld potential (FP) responses to orthodromic synaptic stimulation, the e xtracellular DC potential, and the extracellular Ca2+ concentration ([ Ca2+](o)] were measured simultaneously in layers II/III of primary som atosensory cortex. Hypoxia caused a 42 and 55% decrease in the FP resp onse in juvenile and adult cortex, respectively. FP responses recorded in slices from young animals were significantly more resistant to oxy gen deprivation as compared with the juvenile (P < 0.01) and adult age group (P < 0.001) and declined by only 3% in amplitude. In adult cort ex, hypoxia elicited, after 7 +/- 4.5 min (mean +/- SD), a sudden anox ic depolarization (AD) with an amplitude of 14 +/- 6 mV and a duration of 0.89 +/- 0.28 min at half-maximal amplitude. Although the AD onset latency was significantly longer in P5-8 (12.5 +/- 4.9 min, P < 0.001 ) and P14-18 (8.7 +/- 3.2 min, P < 0.002) cortex, the amplitude and du ration of the AD was larger in young (45.7 +/- 7.6 mV, 2.19 +/- 0.71 m in, both P < 0.001) and juvenile animals (29.9 +/- 9.1 mV, P < 0.001, 0.96 +/- 0.26 min, P > 0.05) when compared with the adults. The hypoxi a-induced [Ca2+](o) decrease was significantly (P < 0.002) larger in y oung cortex (1,115 +/- 50 mu M) as compared with the adult (926 +/- 10 7 mu M). Prolongation of hypoxia after AD onset for >5 min elicited in young and juvenile cortex a long-lasting AD with an amplitude of 40.5 mV associated with a decrease in [Ca2+](o) bp >1 mM. On reoxygenation , only slices from these age groups showed spontaneous repetitive spre ading depression in 3 out of 26 cases. In adults, the same protocol ca used a significantly (P < 0.05) smaller and shorter AD and never a spr eading depression. However, recovery in synaptic transmission after th is long-term hypoxia was better in young and juvenile cortex, indicati ng a prolonged or even irreversible deficiency in synaptic function in mature animals. Application of ketamine caused a 49% reduction in the initial amplitude of the AD in juvenile cortex but did not significan tly affect the AD in slices from adult animals. These data indicate th at the young and juvenile cortex tolerates much longer periods of oxyg en deprivation as compared with the adult, but that a sufficiently lon g hypoxia causes severe pathophysiological activity in the immature co rtex. This enhanced sensitivity of the immature cortex is at least par tially mediated by activation of N-methyl-D-aspartate receptors.