Introduction Electrical stimulation of the cerebellar fastigial nucleus (FN) in rat reduces by 50% , the volume of a focal ischemic infarction produced by occlusion of the middle cerebral artery (MCAO). 1,2 The area of salvage corresponds to the ischemic penumbra 3 , i.e. that region of the infarct surrounding an ischemic core wherein regional cerebral blood flow (rCBF) is partially reduced, and regional cerebral glucose utilization (rCGU) is elevated. 4 The effect of 1 h of stimulation is long-lasting and reversible, with pro- tection persisting for up to 10 days. 5 The mechanism of salvage cannot be attributed to changes in rCBF or rCGU 2,4,5 but rather appears related, in part, to long-lasting changes in electrical excitability 6 and/or immune reactivity of cerebral vessels. 2 It is not known whether excitation of the FN is effective against other forms of cerebral injury. In the present study we investigated whether FN stimula- tion can protect pyramidal cells of the hippocampal CA1 group from the delayed degeneration elicited by transiently interrupting blood flow to the brain. We report that FN stimulation reduces the magni- tude of ischemic neuronal degeneration by almost 60% . Thus central neurogenic neuroprotection elicited from the cerebellum may represent a more generalized mechanism by which the brain may protect itself from injury. Materials and Methods The experimental protocol was approved by the Institutional Animal Care and Use Committee of Cornell University Medical College. Adult male Sprague–Dawley rats weighing 350–400 g were anes- thetized with 5% halothane in 100% O 2 . Anesthesia was reduced to 2% during surgery: efficacy was monitored by observing that arterial pressure (AP) was not elevated and the EEG was not activated during the procedures in response to pinch. Polyethylene catheters were inserted in each femoral artery to record AP and measure blood gases. Body temperature was maintained at 37C by a heating pad controlled by an electro-thermometer connected to a rectal probe. Both carotid arteries were mobi- lized through a midline incision in the neck and loose ligatures were placed around them. The animals were placed in a stereotaxic frame with the bite bar posi- tioned at 11 mm below stereotactic zero. The dorsal surface of the skull, occipital bone and first two cervical vertebrae were exposed. The paraspinal muscles were separated from the midline and, under an operating microscope, the right and left foramina alarae of the first cervical vertebra exposed. An elec- trocautery needle 0.5 mm in diameter was inserted through each foramen and each vertebral artery was cauterized. A laser-Doppler flowmeter (LDF) probe (tip diameter 1.0 mm) was positioned over the sensori- motor cortex (2 mm caudal and 2 mm lateral to the Clinical Neuroscience and Neuropathology 1111 2 3 4 5 6 7 8 9 10111 1 2 3 4 5 6 7 8 9 20111 1 2 3 4 5 6 7 8 9 30111 1 2 3 4 5 6 7 8 9 40111 1 2 3 4 5 6 7 8 9 50111 1 2 3 4 5 6111p © Rapid Science Ltd Vol 9No 530 March 1998 819 WE investigated whether electrical stimulation of the cerebellar fastigial nucleus (FN) can protect pyramidal neurons of the CA1 zone of dorsal hippocampus from delayed neuronal death caused by global ischemia. Stimulation of the FN for 1 h prior to transient 4-vessel occlusion in anesthetized rats salvaged 57% (p < 0.01) of pyramidal neurons from degeneration. This effect could be preconditioned. Sham simulation of FN or stimula- tion of the rostral ventrolateral medulla (RVL) were without effect( p > 0.5). Excitation of intrinsic neuronal pathways represented in FN can protect central neurons from global as well as focal ischemic degeneration. The brain contains systems designed to protect it from ischemia by mechanisms of central neurogenic neuro- protection acting independently of actions on cerebral blood flow. NeuroRepor t 9: 819–824 © 1998 Rapid Science Ltd. Key words : CA1; Conditioned neuroprotection; Delayed neuronal death; Electrical stimulation; Fastigial nucleus; Global ischemia; Neuroprotection Stimulation of cerebellum protects hippocampal neurons from global ischemia Eugene V. Golanov, CA Fang Liu and Donald J. Reis Division of Neurobiology, Department of Neurology and Neuroscience, Cornell University Medical College, 411 E 69 Street, New York, NY 10021, USA CA Corresponding Author Website publication 11 M arch 1998 NeuroReport 9, 819–824 (1998)