Brief electrical stimulation of cerebellar fastigial nucleus conditions long-lasting salvage from focal cerebral ischemia: conditioned central neurogenic neuroprotection

Reis, Donald J.; Kobylarz, Keith; Yamamoto, Seiji; Golanov, Eugene V.

doi:10.1016/s0006-8993(97)01017-2

Cited by 59 publications

(65 citation statements)

References 20 publications

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“…Electrical stimulation of the cerebellar fastigial nucleus (FN) for 1 h was found to elicit a marked and long-lasting increase in the brain tolerance to insults, with features suggesting that the resulting tolerance was similar to that achieved by other preconditioning methods: 1) effective protection against different insults, including global and focal ischemia (141,333) and excitotoxicity (139); 2) delayed protection against MCAO was maximal 3 days after FN stimulation; 3) decreased susceptibility of brain cells to apoptosis in vitro (462); and 4) decreased inflammatory reactivity in the brain (129). However, the most interesting finding within the context of this subsection was that FN stimulation at 3 days before MCAO also markedly reduced the development of peri-infarct depolarizations (142).…”

Section: Ischemic Tolerance and Peri-infarct Depolarizing Eventsmentioning

confidence: 99%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

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Ischemic tolerance describes the adaptive biological response of cells and organs that is initiated by preconditioning (i.e., exposure to stressor of mild severity) and the associated period during which their resistance to ischemia is markedly increased. This topic is attracting much attention because preconditioning-induced ischemic tolerance is an effective experimental probe to understand how the brain protects itself. This review is focused on the molecular and related functional changes that are associated with, and may contribute to, brain ischemic tolerance. When the tolerant brain is subjected to ischemia, the resulting insult severity (i.e., residual blood flow, disruption of cellular transmembrane gradients) appears to be the same as in the naive brain, but the ensuing lesion is substantially reduced. This suggests that the adaptive changes in the tolerant brain may be primarily directed against postischemic and delayed processes that contribute to ischemic damage, but adaptive changes that are beneficial during the subsequent test insult cannot be ruled out. It has become clear that multiple effectors contribute to ischemic tolerance, including: 1) activation of fundamental cellular defense mechanisms such as antioxidant systems, heat shock proteins, and cell death/survival determinants; 2) responses at tissue level, especially reduced inflammatory responsiveness; and 3) a shift of the neuronal excitatory/inhibitory balance toward inhibition. Accordingly, an improved knowledge of preconditioning/ischemic tolerance should help us to identify neuroprotective strategies that are similar in nature to combination therapy, hence potentially capable of suppressing the multiple, parallel pathophysiological events that cause ischemic brain damage.

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Section: Ischemic Tolerance and Peri-infarct Depolarizing Eventsmentioning

confidence: 99%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

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“…5,6 Interestingly, neuroprotection is long-lasting, with protection seen when the MCA is occluded 3 days after only 1 hour of fastigial nucleus stimulation. 23 In this case, neuroprotection is not mediated by changes in blood flow in the ischemic territory or by decreases in metabolic demand in the ischemic or peri-infarct territory, 5 but may be attributable to suppression of the inflammatory reaction 24,25 along with suppression of apoptosis, 26 probably mediated by potassium channels. The only studies that used a stimulus during ischemia used pulsed electromagnetic fields (PEMF).…”

Section: Burnett Et Al Stimulation During Ischemia Decreases Damage 1329mentioning

confidence: 99%

Electrical Forepaw Stimulation During Reversible Forebrain Ischemia Decreases Infarct Volume

Burnett

Shimazu

Szabados

et al. 2006

Stroke

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Background and Purpose-Functional stimulation is accompanied by increases in regional cerebral blood flow which exceed metabolic demands under normal circumstances, but it is unknown whether functional stimulation is beneficial or detrimental in the setting of acute ischemia. The aim of this study was to determine the effect of forepaw stimulation during temporary focal ischemia on neurological and tissue outcome in a rat model of reversible focal forebrain ischemia. Methods-Sprague-Dawley rats were prepared for temporary occlusion of the right middle cerebral artery (MCA) using the filament model. Cerebral blood flow in the MCA territory was continuously monitored with a laser-Doppler flowmeter. Subdermal electrodes were inserted into the dorsal forepaw to stimulate either the forepaw ipsilateral or contralateral to the occlusion starting 1 minute into ischemia and continuing throughout the ischemic period. A neurological evaluation was undertaken after 24 hours of reperfusion, and animals were then euthanized and brain slices stained with 2,3,5-triphenyltetrazolium chloride. Cortical and striatal damage was measured separately. Results-The cortical and striatal infarct volumes were both significantly reduced in the contralateral stimulated group compared with the ipsilateral stimulated group (48% total reduction). There were no statistically significant differences in the neurobehavioral scores between the 2 groups, or in the laser-Doppler flow measurements from the MCA core. Conclusions-Functional stimulation of ischemic tissue may decrease tissue damage and improve outcome from stroke.Although the precise mechanism of this effect remains to be determined, functional stimulation could readily be translated to clinical practice. Key Words: cerebral ischemia, focal Ⅲ electrical stimulation therapy Ⅲ middle cerebral artery occlusion T here remains intense interest in discovering novel neuroprotective therapies for use in acute cerebral ischemia. Most recent research efforts have focused on compounds designed to interfere with the cascade of deleterious events that occur in tissue during and in the minutes and hours after cerebral ischemia. 1 Although many compounds have been investigated, to-date none have proven clinically useful in humans. 2,3 Nonpharmacological treatment techniques, such as hypothermia and hyperoxemia, have also been proposed, 4 but it remains to be seen how they transfer from laboratory to bedside. There are even studies suggesting that electrical stimulation of the cerebellar fastigial nucleus 5,6 before ischemia, or the spinal cord 7-9 weeks and months after the ischemic insult can reduce damage.Functional stimulation is accompanied by an increase in regional cerebral blood flow (CBF) in activated brain regions. We have shown previously in a rat model of graded cerebral ischemia that when CBF is reduced by as much as 90%, forepaw stimulation is still able to elicit an increase in blood flow in the somatosensory cortex, 10 and studies in stroke patients demonstrate that CBF can be activated...

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“…This central neurogenic control of the cerebral circulation resulted from excitation of intrinsic pathways to the brain. According to Reis and Latkowski, many functionally discrete tissues involving in cerebrovascular homeostasis such as subthalamic vasodilator, fastigial nucleus, parasympathetic and sympathetic nerves, located behind mastoid regions [12,13]. Mastoid electrical stimulation might be a valuable method for ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%