Differential effects of hypoxia-ischemia on phosphorylation of the N-methyl-D-aspartate receptor in one- and three-week-old rats.

The effects of transient cerebral hypoxia-ischemia (HI) on phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor were investigated in 7 (P7)- and 21 (P21)-day-old rats. Unilateral HI was induced by ligation of the right common carotid artery and exposure to 8% O2/92% N2 for 120 (P7) or 90 (P21) min. Phosphorylation by protein kinase A (PKA; S897) and PKC (S896 and S890) was depressed in the ipsilateral hemisphere relative to both naive controls and the contralateral hemisphere immediately following HI at both ages. At P7, but not P21, reperfusion resulted in an initial recovery to control phosphorylation levels at all 3 sites followed by a secondary decline. At both ages, pS896 was less than control values after 24 h of recovery, whereas pS890 had returned to control levels by this time. pS897 recovered to control levels by 24 h in P21 animals but not in P7 animals. Differential effects of HI on phosphorylation of the NMDA receptor at P7 and P21 may contribute to age-related changes in sensitivity to HI.