Electrical Stimulation of Cerebellar Fastigial Nucleus Reduces Ischemic Infarction Elicited by Middle Cerebral Artery Occlusion in Rat

Abstract

Electrical stimulation of the cerebellar fastigial nucleus (FN) globally and profoundly increases cerebral blood flow via a cholinergic mechanism. In cerebral cortex, the vasodilation is unassociated with alterations in cerebral glucose utilization, a condition favoring protection against cerebral ischemia. We sought to determine whether FN stimulation would modify the size of the focal ischemic infarction resulting from occlusion of the middle cerebral artery (MCA). The MCA was occluded in anesthetized rats of the spontaneously hypertensive (SHR) or Sprague-Dawley (SD) strains with or without 1 h of electrical stimulation of the FN. Twenty-four hours later, rats were killed and the volume of the infarction established in thionin-stained sections. in SHRs, FN stimulation reduced by 40% the well-established cortical and partially subcortical infarctions elicited by occlusion of the MCA (from 186 +/- 35.2 to 113 +/- 47.1 mm3, mean +/- SD, n = 15; p less than 0.001). The zone of retrieval was anatomically constant, consisting of a rim of cortex dorsal and ventral to the infarction and medially within the thalamus and striatum corresponding to the penumbral zone described by others. The effect was comparable in rats of the SD strain having smaller infarctions. The effect of FN stimulation appears to be selective for the FN system in that it is not evoked by stimulation of the dentate nucleus and is blocked by systemic administration of atropine (1.0 mg/kg). We conclude that excitation of an intrinsic system in brain represented in the rostral FN has the capacity to reduce substantially an ischemic infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of Nitric Oxide Synthesis Increases Focal Ischemic Infarction in Rat

“…NO has been proposed to modulate the release of several neurotransmitters (Moncada et aI., 1989;Toda and Okamoto, 1990;Crossin, 1991), some of which may counteract the action of L-Glu. That neurotransmitter-regulated events may play a role in neuroprotection in focal cerebral infarction has been demonstrated by the observation that focal ischemic infarction elicited by occlusion of the MCA in rat may be reduced by almost 50% by excitation of intrinsic neuronal net works related to the cerebellar fastigial nucleus (Berger et a!., 1990;Reis et a!., 1991).…”

“…The methods for preparation of rats, for instrumenta tion, for measurement of blood gases, glucose, and he matocrit (Hct), for production of focal cerebral ischemia by occlusion of the MCA, for computation of infarct vol ume, and for recording of regional CBF (rCBF) by laser Doppler flowmetry (LDF) have been described in detail in other publications from our laboratory (Iadecola and Reis, 1990;Reis et at., 1991;Maiese et ai., 1992) and will only be summarized below.…”

“…The MCA was exposed for occlusion distal to the len ticulostriatal branches by a method (Reis et at., 1991) modified from that of Tamura et al (1981). Animals were rotated in the stereotaxic frame to a lateral position with the right side facing upward.…”

Transcutaneous Electrical Stimulation on Mastoid Regions Increased Mean Flow Velocity in Patients with Ischemic Stroke

“…According to Glickstein, fastigial nucleus (FN) had play an important roles in cerebrovascular regulation. Several studies suggested that electrical stimulation of the FN could markedly elevate rCBF globally in the brain [15,16]. These studies also showed that in many brain regions including the cerebral cortex, the increase in rCBF elicited from FN stimulation was not associated with the changes of local cerebral metabolism.…”

Fastigial Stimulation Increases Ischemic Blood Flow and Reduces Brain Damage after Focal Ischemia

“…In analogy with other interventions for brain protection (Choi, 1990), FN stimulation could reduce tissue damage by improving CBF to the ischemic tissue and decreasing the degree of oligemia (hemodynamic mechanism). Alternatively, FN stimulation might increase the resistance of brain cells to ischemic damage by releasing protec tive agents in the ischemic territory, possibly neu rotransmitters (cytoprotective mechanism) (Reis et al, 1991). The finding that FN stimulation increases CBF in the ischemic territory strongly suggests that the mechanism of the protection is "hemody namic."…”