Stimulation Of Cerebellar Fastigial Nucleus Research Articles

Increased cerebral cortex activation in stroke patients during electrical stimulation of cerebellar fastigial nucleus with functional near-infrared spectroscopy.

Electrical stimulation of the cerebellar fastigial nucleus (FNS) has been shown to protect animals against cerebral ischemic injury. However, the changes in cortical activation as a response to FNS have not been illustrated in humans. This study aims to detect functional connectivity changes in the brain of stroke patients, and investigate the cortical activation caused by FNS through measuring the oxygenated hemoglobin concentration (HBO) in the cerebral cortex of stroke patients and healthy controls (HCs). This study recruited 20 patients with stroke and 20 HCs with all the following factors matched: age, gender and BMI. The experiment session was made up of the pre-task baseline, FNS task period, and post-task baseline. FNS task period contains 5 blocks, each block encompassing the resting state (30 s) and the FNS state (30 s). HBO signals were acquired by functional near-infrared spectroscopy (fNIRS) from the Prefrontal Cortex (PFC), the Motor Cortex (MC) and the Occipital Cortex (OC) throughout the experiment. The Pearson correlation coefficient was used to calculate the resting-state functional connectivity strength between the two groups, and the general linear model (GLM) was used to calculate the activation of 39 fNIRS channels during FNS in stroke patients and HCs, respectively. The coupling strength of stroke patients were significantly decreased in the following regions: right MC and left MC (t = 4.65, p = 0.0007), right MC and left OC (t = 2.93, p = 0.04), left MC and left OC (t = 2.81, p = 0.04). In stroke patients, the changes in cerebral oxygenated hemoglobin (ΔHBO) among 12 channels (CH) in the bilateral PFC and bilateral MC regions were significantly increased during the FNS state (FDR corrected p < 0.05) compared with the resting state. In HCs, only 1 channel was increased (FDR corrected p < 0.05) in the left PFC during FNS. By using the FNS and fNIRS techniques, the characteristics of functional connectivity were found to decrease in stroke patients. It was also noticed that FNS activates the PFC and MC regions. These findings may help to guide functional rehabilitation in stroke patients.

Abstract WP389: Anatomical Trajectory for Focused Ultrasound Stimulation of Fastigial Nucleus for Neuroprotection in Human Cerebral Ischemia

Introduction: In multiple animal models of ischemic stroke, cerebellar fastigial nucleus stimulation (FNS) via implanted electrode has been shown to exert strong neuroprotective and collateral enhancement effects. Translational studies of FNS have been precluded due to the invasive nature of direct electrical stimulation. Recently, low-intensity focused ultrasound pulsation (LIFUP) has been used to stimulate deep hemispheric targets. Identifying achievable anatomic trajectories for LIFUP delivery is required for human trials. Method: Sagittal brain MRI T1 from 10 patients were analyzed. Potential pathways from the suboccipital (SO) region (transducer placement site) to the roof of the 4 th ventricle (location of FN) were traced, evaluating paths both via the thinnest portion of the occipital bone (OB) and via the transforaminal window (TFW). Interindividual variations in trajectory distances (cm), thickness of the OB through which the beam passes (cm), and the projected neck flexion degree from neutral position required to achieve a TFW path were measured. Results: An achievable anatomic pathway for stimulation of the FN via LIFUP was identified in 100% of patients (Fig 1). In standard MR positioning, 90% had an available path through thin portions of the OB and 10% had a projected path through TFW. The mean distance from the skin at the SO region to the roof of 4 th ventricle/FN was 7.2 cm (± 0.64cm). The mean OB thickness traversed by the beam was 0.3cm (±0.1). The projected required neck flexion to enable a TFW in all subjects was mean 9.3° (±5°). Conclusions: The distance for the LIFUP beam to travel from skin surface to FN via a suboccipital approach is well within the LIFUP penetration depth and all individuals had an accessible trajectory via the TFW through attainable degrees of head flexion, affording minimal ultrasonic energy dispersion and maximal focality. Ultrasound stimulation of fastigial nucleus is a feasible treatment strategy in human acute ischemic stroke.

Cerebellar Fastigial Nucleus Stimulation in a Chronic Unpredictable Mild Stress Rat Model Reduces Post-Stroke Depression by Suppressing Brain Inflammation via the microRNA-29c/TNFRSF1A Signaling Pathway.

BackgroundWe previously reported that cerebellar fastigial nucleus stimulation reduced post-stroke depression in a rat model by reducing inflammation. This study aimed to investigate the molecular inflammatory signaling pathways associated with cerebellar fastigial nucleus stimulation in an established rat model of post-stroke depression.Material/MethodsTwenty-four Sprague-Dawley rats included a sham group (N=6), an untreated stroke group (N=6), an untreated post-stroke depression model group (PSD) (N=6), and the model group treated with cerebellar fastigial nucleus stimulation (FNS) (N=6). The rat stroke model involved occlusion of the middle cerebral artery occlusion (MCAO). Post-stroke depression model was established using chronic unpredictable mild stress treatment and was verified using an open field test. Real-time polymerase chain reaction (PCR) and Western blot compared expression levels of microRNA-29c (miR-29c), miR-676, TNFRSF1A, tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in cerebellar tissue. U251 human glioblastoma cells and SH-SY5Y human neuroblastoma cells were studied in vitro.ResultsCerebellar fastigial nucleus stimulation reduced behaviors associated with depression in the rat model, upregulated the expression of miR-29c, and reduced the expression of TNFRSF1A and inflammatory cytokines, and mildly reduced neuronal apoptosis. Bioinformatics data analysis identified a regulatory relationship between miR-29c and TNFRSF1A. SH-SY5Y cells treated with a miR-29c mimic, or TNFRSF1A short interfering RNA (siRNA), identified a negative regulatory relationship between TNFRSF1A and miR-29c.ConclusionsIn a rat model, cerebellar fastigial nucleus stimulation reduced the expression of TNFRSF1A by upregulating miR-29c expression, which suppressed the expression of inflammatory cytokines, resulting in reduced severity of post-stroke depression.

Fastigial nucleus stimulation ameliorates cognitive impairment via modulating autophagy and inflammasomes activation in a rat model of vascular dementia.

It has been reported that the fastigial nucleus (FSN) plays an important role in the development of vascular dementia (VD). Both autophagy and inflammation are functionally involved in the pathogenesis of VD. In this study, we aimed to evaluate the therapeutic effect of electrical cerebellar fastigial nucleus stimulation (FNS) in VD treatment, as well as the effect of FNS on autophagy and inflammation. A Morris water maze was used to evaluate the effect of FNS on the learning and memory ability of VD rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to study the apoptosis status of neuron cells in different groups of rats. In addition, immunohistochemistry (IHC) assay, real-time polymerase chain reaction, and Western blot analysis were carried out to measure the expression of various factors involved in autophagy and inflammation. Rats with artery occlusion or FSN damages showed longer escape latency and spent less time in the target quadrant. In addition, FNS treatment could help to partly recover the lost learning and memory ability in VD rats. Meanwhile, FNS treatment could alleviate neuron cell apoptosis by downregulating light chain 3-II expression and NLRP3 expression. In addition, the expression of caspase-1, interleukin 1β (IL-1β), and IL-18 was markedly reduced in VD rats treated by FNS. FNS treatment exerted a therapeutic effect during VD treatment by suppressing the autophagy process and by inhibiting inflammatory responses, thus alleviating neuron cell apoptosis and reducing the severity of VD.

Oxiracetam or fastigial nucleus stimulation reduces cognitive injury at high altitude.

BackgroundCognitive impairment is common in people travelling to high altitude. Oxiracetam and electrical stimulation of cerebellar fastigial nucleus may have beneficial impacts. This study was to investigate the effects of preconditioning with Oxiracetam or fastigial nucleus stimulation (FNS) on cognitive decline following the ascension to high altitude.MethodsThe study was conducted on 60 male military voluntary members who were divided into control group, Oxiracetam group, and fastigial nucleus stimulation group. Transcranial doppler sonography, auditory evoked potential, electroencephalogram (EEG), and cognitive assessments were performed.ResultsPeople could still suffer cognitive dysfunction at 4,000 m high altitude despite that they have lived at 1,800 m altitude for several years. The 4,000 m altitude environment also prolonged P300 and N200 latencies. Both Oxiracetam and FNS improved cognitive function, reduced the prolonged latencies of Event Related Potentials (P300 and N200), decreased the average velocity of brain arteries, and enhanced EEG power spectral entropy at 4,000 m altitude.ConclusionsNeurophysiological evidences suggest the underlying mechanism of cognitive impairments. Both Oxiracetam and FNS can reduce cognitive decline post arrival at high altitude. They could be a potential pretreatment method for cognitive dysfunction resulted from high altitude.

Electrical stimulation of cerebellar fastigial nucleus protects against cerebral ischemic injury by PPARγ upregulation

Objective: Cerebellar fastigial nucleus stimulation (FNS) has been shown to protect against cerebral ischemic injury. Peroxisome proliferator activator receptor gamma (PPARγ) has been reported to cause neuroprotection in animal models of stroke. The present study was performed to explore the neuroprotective mechanisms of FNS treatment in experimental stroke.Methodology: Adult male Sprague-Dawley (SD) rats preconditioned through transfection with either PPARγ-small hairpin RNA (shRNA) or lentiviral vector without shRNA and surgically subjected to middle cerebral artery occlusion and reperfusion subsequently received FNS treatment. The expression of PPARγ after FNS treatment was measured using western blotting and immunohistochemistry. Subsequently, the neuronal apoptosis, neurological deficits scores, and cerebral infarction were also evaluated. Additionally, the influence of FNS on the pro-inflammatory cytokines expression were determined by ELISA.Results: We found that FNS significantly upregulated PPARγ expression, attenuated apoptosis and inflammatory response, and reduced infarct volume. The protective effect of FNS was abrogated by PPARγ-shRNA.Conclusion: Our results as described above suggested that FNS confers neuroprotection by upregulated PPARγ.

The Effect of Pre-Condition Cerebella Fastigial Nucleus Electrical Stimulation within and beyond the Time Window of Thrombolytic on Ischemic Stroke in the Rats.

ObjectiveTo investigate the effect of neurogenic neuroprotection conferred by cerebellar fastigial nucleus stimulation (FNS) and the role of PPARγ- mediated inflammation in a rat model of cerebral ischemia reperfusion.MethodsAfter a continuous 1 hour fastigial nucleus electric stimulation, the male Sprague Dawley (SD) rats were given middle cerebral artery occlusion (MCAO) for 1, 3, 6, 9, 12 and 15 hours undergoing reperfusion with intravenous recombinant tissue plasminogen activator (rt-PA), while the control group received without FNS. After 72h of reperfusion, the neurological deficits, infarct volume and brain edema were evaluated. The brain tissue in ischemic penumbra was determined the myeloperoxidase (MPO) activity by a spectrophotometer and expression of PPARγ was measured by Rt-PCR and Western blotting.ResultsOur findings showed that FNS group had significantly reduced infarct volume and brain edema, and improved neurological deficits compared with the control group, especially in 6h and 9h reperfusion subgroups(p<0.05). The expression levels of PPARγ increased gradually and the peak may be before and after 9h reperfusion, the 3h, 6h, 9h, 12h and 15h reperfusion subgroups were higher than each control group(p<0.05). The MPO activity of 6h, 12h and 15h reperfusion subgroups were higher than each control group(p<0.05).ConclusionsThe neuroprotective effects of FNS have been shown to prolong the therapeutic window in cerebral ischemia/reperfusion, which might be related to the PPARγ mediated-inflammation in penumbral region.

Electrical stimulation of cerebellar fastigial nucleus: mechanism of neuroprotection and prospects for clinical application against cerebral ischemia.

For around two decades, electrical fastigial nucleus stimulation (FNS) has been demonstrated to induce neuroprotection involving multiple mechanisms. In this review, we summarize the protective effects of FNS against cerebral ischemia through the inhibition of electrical activity around the lesion, excitotoxic damage on neurons, and brain inflammatory response, as well as apoptosis. Moreover, FNS has been reported to promote nerve tissue repair, reconstruction, and neurological rehabilitation and improve stroke-related complications including poststroke cognitive dysfunction, depression, and abnormal heart rate variability. We thus further discuss the potential of FNS for clinical applications. Given the absence of any risk of inducing sublethal damage, FNS may offer a new approach to preconditioned neuroprotection against cerebral ischemia.

Electrical stimulation of cerebellar fastigial nucleus promotes the expression of growth arrest and DNA damage inducible gene β and motor function recovery in cerebral ischemia/reperfusion rats

This study focused on the effects of electrical stimulation of cerebellar fastigial nucleus on the expression of growth arrest and DNA damage inducible gene β (Gadd45β) and on motor function recovery after focal cerebral ischemia/reperfusion (I/R) in rats. Sprague–Dawley (SD) rats were randomly divided into 4 groups: sham I/R (control group), I/R (I/R group), I/R with sham stimulation and I/R with electrical stimulation at 6h, 12h, 24h, 2d and 3d after I/R. Cerebral ischemia and reperfusion was established by nylon monofilament occlusion method. Fastigial nucleus (FN) electrical stimulation was applied at 2h after ischemia for 1h. The changes in the expression of Gadd45β were analyzed by immunohistochemistry, real-time polymerase chain reaction (PCR) and Western-blot respectively. Another group of rats were divided into the same 4 groups. Montoya staircase test score was used to test the motor function of affected forelimb. The levels of Gadd45β were significantly elevated after I/R injury. FN electrical stimulation treatment elevated the expression of Gadd45β further and improved motor function recovery. These results suggest that FN electrical stimulation can promote the expression of Gadd45β and motor function recovery after focal cerebral ischemia.

Electrical stimulation of cerebellar fastigial nucleus up-regulates uncoupling protein 4 and stabilizes mitochondrial membrane potential in the cortex

Electrical stimulation of cerebellar fastigial nucleus up-regulates uncoupling protein 4 and stabilizes mitochondrial membrane potential in the cortex

Protective effect of chemical stimulation of cerebellar fastigial nucleus on stress gastric mucosal injury in rats

AimsWe investigated the protective effects of chemical stimulation of cerebellar fastigial nucleus (FN) on stress gastric mucosal injury (SGMI) and its possible neuro-regulatory mechanisms in rats. Main methodsChemical stimulation, electrical stimulation, chemical ablation, electrolytic lesion, and microinjection were used to investigate the effects of FN simulation on SGMI. The model of SGMI was established by restraint and water (21±1°C)-immersion (RWI) for 3h in rats. The gastric mucosal injury index indicated the severity of gastric mucosal injuries. Key findingsWe showed that microinjection of L-glutamic acid into the FN or electrical stimulation of the FN markedly attenuated SGMI. Either chemical lesion of the FN or electrical ablation of the decussation of superior cerebellar peduncle (DSCP) obviously aggravated SGMI. The protective effect of FN stimulation on SGMI was reversed after chemical ablation of the lateral hypothalamic area (LHA). The protective effect of FN was prevented by pretreatment with the glutamic acid decarboxylase antagonist, 3-MPA into the FN or GABAA receptor antagonist, bicuculline into the LHA. The protective effect of FN was abolished by pretreatment with sympathectomy. The discharge frequency of greater splanchnic nerve (GSN) was decreased and gastric mucosal blood flow (GMBF) was increased after chemical stimulation of FN. These results indicate that the FN participates in regulation of SGMI, and is a specific area in the CNS for exerting protective effects on the SGMI. The DSCP, LHA and peripheral sympathetic nerve may be involved in this process. SignificanceOur findings might provide a new and improved understanding of the cerebellar function and an effective treatment strategy for stress gastric mucosal injury.

Effect of electrical stimulation of cerebellar fastigial nucleus on the contents of monoaminergic transmitters in frontal lobe of rats with depression

Objective To investigate the effect of electrical stimulation of cerebellar fastigial nucleus (FN) on the contents of monoaminergie transmitters in frontal lobes of rats with depression, and to explore the pathway and mechanism of electrical stimulation of cerebellum in treating depression. Methods A total of 30 Wistar rats were used tO establish the animal depression model by exposure to chronic stressing circumstances. Electrical stimulation delivered to the left cerebellar FN or left dentate nucleus (DN) for 1 h was used as the intervention. The contents of serotonin (5-HT), noradrenalin (NE) and dopamine (DA) in frontal lobe were determined with fluorospectropho-tometry. Results Compared with normal control group, the contents of 5-HT and NE in bilateral frontal lobes of depression model rats decreased significantly (P 0. 05), but significant increases of 5-HT and NE in right and left frontal lobes were observed in depression model rats after stimulation of FN (P < 0.05, P < 0.001; P <0.05, P <0.01), with the increase in right lobe more significant than in left lobes (P <0.05). In de-pression model rats underwent DN stimulation, significant increase of contents of all three monoaminergic transmitters in frontal lobes was observed. Conclusion ElectrieM stimulation of cerebellar FN can increase the contents of 5-HT and NE in frontal lobes of rats with depression, and this suggest that electrical stimulation might have therapeutic effect to depression. Key words: Electrical stimulation; Cerebellar fastigial nucleus; Depression; Monoaminergic transmit-ters; Rat

Low-frequency stimulation of cerebellar fastigial nucleus inhibits amygdaloid kindling acquisition in Sprague–Dawley rats

Low-frequency stimulation (LFS) of the kindling focus or the piriform cortex inhibits kindling epileptogenesis, but whether LFS of brain targets outside the limbic system has anticonvulsive actions remain unknown. The current study was designed to investigate the effect of LFS of the cerebellar fastigial nucleus (FN) on seizure progression induced by amygdaloid kindling. Stimulation at 1 Hz (15-min train of 0.1-ms pulses, 100 muA), but not at 3 Hz, in the ipsilateral FN immediately after the daily kindling stimulus (1-s train of 1-ms pulses at 60 Hz and 100-300 muA) significantly inhibited the seizure stage and afterdischarge duration in kindling acquisition. Neither 1 Hz nor 3 Hz stimulation of the contralateral FH had any significant effect. It is interesting that delaying delivery (immediately after the cessation of afterdischarge) of LFS in the ipsilateral FN accelerated the rate of kindling acquisition compared to controls. Our study suggests that LFS of targets outside the limbic system, such as the FN, may have a significant anti-epileptogenic action, and the effects of LFS depend on the frequency and timing of stimulation.

Mitochondria are involved in the neurogenic neuroprotection conferred by stimulation of cerebellar fastigial nucleus

Activation of neural pathways originating in the cerebellar fastigial nucleus (FN) protects the brain from the deleterious effects of cerebral ischemia and excitotoxicity, a phenomenon termed central neurogenic neuroprotection. The neuroprotection is, in part, mediated by suppression of apoptosis. We sought to determine whether FN stimulation exerts its anti-apoptotic effect through mitochondrial mechanisms. Mitochondria were isolated from the cerebral cortex of rats in which the FN was stimulated for 1 h (100 microA; 1 s on/1 s off), 72 h earlier. Stimulation of the dentate nucleus (DN), a brain region that does not confer neuroprotection, served as control. Mitochondria isolated from FN-stimulated rats exhibited a marked increase in their ability to sequester Ca2+ and an increased resistance to Ca2+-induced membrane depolarization and depression in respiration. FN stimulation also leads to reduction in the release in cytochrome c, induced either by Ca2+ or the mitochondrial toxin mastoparan. Furthermore, in brain slices, FN stimulation reduced the staurosporine-induced insertion of the pro-apoptotic protein Bax into the mitochondria, a critical step in the mitochondrial mechanisms of apoptosis. Collectively, these results provide evidence that FN stimulation protects the mitochondria from dysfunction induced by Ca2+ loading, and inhibits mitochondrial pathways initiating apoptosis. These mitochondrial mechanisms are likely to play a role in the neuroprotection exerted by FN stimulation.

Electrical stimulation of cerebellar fastigial nucleus stabilizes mitochondrial membrane potential in neurons

Electrical stimulation of cerebellar fastigial nucleus stabilizes mitochondrial membrane potential in neurons

CONTRIBUTION OF CEREBRAL NITRIC OXIDE TO BLADDER OVERACTIVITY AFTER CEREBRAL INFARCTION IN RATS

We investigated the contribution of cerebral nitric oxide to neurogenic voiding dysfunction after cerebral infarction. The left mid cerebral artery in female Sprague-Dawley rats was occluded with 4-zero monofilament nylon thread. Bladder activity was monitored during infusion cystometrography. Time or dose dependent effects of intracerebral ventricular administration of the nonselective nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), were investigated in conscious, sham operated and cerebral infarcted rats. The selective neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl) imidazole was also administered to determine the participation of nitric oxide synthase subtypes. Cross-sectional infarct area was measured and infarct volume was calculated 12 hours after mid cerebral artery occlusion. Bladder capacity was reduced by 54% 30 minutes after mid cerebral artery occlusion. L-NAME significantly increased bladder capacity in a dose and time dependent manner in cerebral infarcted rats but had no effect on sham operated rats. L-NAME (50 microg./kg.) administered 3 or 5 hours after occlusion significantly increased bladder capacity. This effect of L-NAME was reversed by injecting 250 microg. L-arginine per rat, which alone did not produce any significant change in bladder capacity in cerebral infarcted rats. Administration of 1-(2-trifluoromethylphenyl) imidazole also significantly increased bladder capacity in these rats. On the other hand, 5 microg. of the nitric oxide donor FK-409 per rat reduced bladder capacity for 10 to 15 minutes. None of the drugs affected infarct volume. These results indicate that supraspinal nitric oxide has an important role in bladder overactivity after cerebral infarction but it does not affect normal micturition in rats. This finding suggests a central mechanism sensitive to nitric oxide for bladder overactivity after cerebral infarction.

Electrical stimulation of cerebellar fastigial nucleus protects rat brain, in vitro, from staurosporine-induced apoptosis.

Electrical stimulation of the cerebellar fastigial nucleus (FN) elicits a prolonged ( approximately 10 days) and substantial (50-80%) protection against ischemic and excitotoxic injuries. The mechanism(s) of protection are unknown. We investigated whether FN stimulation directly protects brain cells against apoptotic cell death in an in vitro rat brain slice culture model. Rats were electrically stimulated in FN or, as control, the cerebellar dentate nucleus (DN). Coronal slices through the forebrain were explanted, exposed to staurosporine, harvested, and analyzed for caspase-3 activity by a fluorescence assay. FN, but not DN, stimulation significantly reduced staurosporine-induced caspase-3 activity by 39 +/- 7% at 3 h, 31 +/- 3% at 6 h and 26 +/- 4% at 10 h of incubation. Immunocytochemistry revealed FN-specific reductions in activated caspase-3 mainly in glial-like cells throughout the forebrain. FN stimulation also results in a 56.5% reduction in cytochrome c release upon staurosporine incubation. We conclude that neuroprotection elicited from FN stimulation can directly modify the sensitivity of brain cells to apoptotic stimuli and thereby suppress staurosporine induced apoptosis in adult rat brain slices. This model indicates that neuroprotection can be studied in vitro and provides new insight into the potential role of glial cells in ischemic protection of neurons induced by FN stimulation.

Stimulation of the subthalamic vasodilator area and fastigial nucleus independently protects the brain against focal ischemia

We investigated whether stimulation of the functionally discrete subthalamic region, subthalamic cerebrovasodilator area (SVA), which increases cerebral blood flow (CBF) when excited, would, like stimulation of cerebellar fastigial nucleus (FN), produce central neurogenic neuroprotection. A 1-h electrical stimulation of SVA or FN reduced infarctions triggered by permanent occlusion of middle cerebral artery (MCA) by 48–55% in Sprague–Dawley rats and by 59% in Fisher rats. The salvaging effect of SVA stimulation, similar to FN, was long lasting and reduced the volume of infarctions placed 72 h or 10 days later by 58 and 26%, respectively, in Fisher rats. Bilateral lesioning of FN neurons by the microinjection of ibotenic acid 5 days before SVA stimulation did not affect SVA-evoked neuroprotection. Bilateral lesions of SVA neurons administered 5 days before FN stimulation had no effect on FN-induced neuroprotection but reversed the stimulus-locked increase in CBF accompanying FN stimulation. This study demonstrates that (1) excitation of neurons and/or fibers projecting through the SVA reduces ischemic infarctions as substantially as excitation of FN neurons; (2) the effects are long-lasting and not attributable to increases in cerebral blood flow, changes in blood gases or brain temperature, or rat strain; (3) the neuroprotective effects of SVA and FN stimulation are mutually independent and (4) FN-evoked cerebrovasodilation is mediated by SVA neurons. The SVA and FN are part of a neuronal system in CNS, which is distributed and, when excited, acts to protect the brain from ischemic injury.

Stimulation of cerebellar fastigial nucleus inhibits interleukin-1beta-induced cerebrovascular inflammation.

Electrical stimulation of the cerebellar fastigial nucleus (FN) in rat protects the brain against ischemia. We studied whether FN could reduce the cerebrovascular inflammation as a mechanism of protection. FN or dentate nucleus (sham controls) was electrically stimulated for 1 h, and 72 h later rats were either injected with interleukin (IL)-1beta into the striata or processed to analyze inflammatory responses in isolated brain microvessels. In striata, IL-1beta induced a recruitment of leukocytes that was reduced by 50% by FN stimulation. In isolated microvessels, IL-1beta induced the transient and dose-dependent upregulation of the mRNAs encoding for the inducible nitric oxide synthase (NOS-2), intercellular adhesion molecule 1 (ICAM-1), and inhibitory kappaB-alpha (IkappaB-alpha), an inhibitor of nuclear factor-kappaB. FN stimulation decreased the upregulation of NOS-2 and ICAM-1 mRNAs, whereas it increased IkappaB-alpha mRNA expression. Dentate nucleus stimulation did not mimic the FN actions. These findings suggest that FN stimulation may render brain microvessels refractory to IL-1beta by overproduction of IkappaB-alpha and support the hypothesis that alteration of microvascular inflammation may contribute to the central neurogenic neuroprotection elicited from the FN.

Electrical stimulation of cerebellar fastigial nucleus fails to rematch blood flow and metabolism in focal ischemic infarctions

Electrical stimulation of the cerebellar fastigial nucleus (FN) in rat (1 h) reduces, by 50%, the infarction produced by occlusion of the middle cerebral artery (MCAO). We investigated whether salvage was associated with elevations in regional cerebral blood flow (rCBF) and/or reductions of regional cerebral glucose utilization (rCGU) in the retrievable zone (RZ). rCGU and rCBF were measured autoradiographically 1 h after MCAO. MCAO reduced rCBF to < 15% in the irretrievable zone (IZ) and ∼ 50% in the RZ ( P < 0.01 for each) while FN stimulation alone globally elevated rCBF by ∼ 60% ( P < 0.01). rCGU was not changed. After MCAO, FN stimulation failed to increase the reduced rCBF but elevated rCGU globally (to ∼30%). Reductions of focal ischemic infarctions by stimulating FN cannot be attributed to changes in rCBF and or rCGU.