Fig. 4. GDNF markedly reduces NO release from the cortex during cerebral ischemia and reperfusion in aged rats.A1, Ischemia was induced by MCA ligation (arrow) for 40 min in this urethane-anesthetized rat. Extracellular NO concentration gradually increased to 20 nmand then declined. A2, Forty minutes after the cerebral ischemia, the arterial ligature was removed (arrow, reperfusion). NO concentration increased to 2.1 nm in this animal. B1, The production of NO during ischemia was reduced by GDNF (0.4 μg/μl × 5 μl) locally applied by microejection 5 min before MCA ligation. B2, NO increases, induced by reperfusion, were also reduced by the local application of GDNF. C1, Intraventricular injection of GDNF (0.4 μg/μl × 10 μl, 30 min before the ligation) and local application (0.4 μg/μl × 5 μl, 5 min before the ligation) attenuated the NO elevation during ischemia and (C2) during reperfusion. D, Bar graphs showing the peak NO concentration during MCA ligation. In the control animals (clear bar), ischemia elicited an average NO release of 17.7 ± 2.4 nm. Local application of GDNF significantly attenuated NO release (hatched bar; one-way ANOVA + Newman–Keuls test). Local plus intracerebroventricular injection of GDNF further diminished NO release (solid bar; p < 0.05). E, Bar graphs showing reperfusion-induced NO release in control (clear bar) and GDNF-pretreated rats (hatched bar). NO release was again significantly diminished by the GDNF pretreatment (p < 0.05).