The Journal of Neuroscience, May 15, 1999, 19(10):4142-4154
Intrinsic Neurons of Fastigial Nucleus Mediate Neurogenic
Neuroprotection against Excitotoxic and Ischemic Neuronal Injury in
Rat
Sara B.
Glickstein,
Eugene V.
Golanov, and
Donald J.
Reis
Department of Neurology and Neuroscience, Cornell University
Medical College, New York, New York 10021
Electrical stimulation of the cerebellar fastigial nucleus (FN)
elevates regional cerebral blood flow (rCBF) and arterial pressure (AP) and provides long-lasting protection against focal and
global ischemic infarctions. We investigated which neuronal element in
FN, perikarya or axons, mediates this central neurogenic neuroprotection and whether it also protects against
excitotoxicity. In anesthetized rats, the FN was stimulated for 1 hr,
and ibotenic acid (IBO) was microinjected unilaterally into the
striatum. In unstimulated controls, the excitotoxic lesions averaged
~40 mm3. Stimulation of FN, but not dentate
nucleus (DN), significantly reduced lesion volumes up to 80% when IBO
was injected 15 min, 72 hr, or 10 d, but not 30 d,
thereafter. In other rats, intrinsic neurons of FN or DN were destroyed
by pretreatment with IBO. Five days later, the FN was stimulated, and
72 hr later, IBO was microinjected into the striatum. Lesions of FN,
but not DN, abolished neuroprotection but not the elevations of rCBF
and AP elicited from FN stimulation. Excitotoxic lesions of FN, but not
DN, also abolished the 37% reduction in focal ischemic infarctions
produced by middle cerebral artery occlusion. Excitation of intrinsic
FN neurons provides long-lasting, substantial, and reversible
protection of central neurons from excitotoxicity, as well as focal
ischemia, whereas axons in the nucleus, probably collaterals of
ramified brainstem neurons, mediate the elevations in rCBF, which do
not contribute to neuroprotection. Long-lived protection against a
range of injuries is an unrecognized function of FN neurons transmitted
over pathways distinct from those regulating rCBF.
Key words:
fastigial nucleus; excitotoxicity; focal cerebral
ischemia; neuroprotection; cerebral blood flow; cerebellum
Copyright © 1999 Society for Neuroscience 0270-6474/99/19104142-13$05.00/0