Spinal cord stimulation reducing infarct volume in a model of focal cerebral ischemia in rats

2003 ◽  
Vol 99 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Oren Sagher ◽  
Dah-Luen Huang ◽  
Richard F. Keep
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Spinal Cord Stimulation ◽  
Focal Cerebral Ischemia ◽  
Doppler Flowmetry ◽  
Content Type ◽  
Baseline Values ◽  
Fine Print

Object. The authors previously showed that spinal cord stimulation (SCS) increases cerebral blood flow in rats, indicating that this technique may be useful in the treatment of focal cerebral ischemia. In the present study, the neuroprotective potential of SCS in the setting of middle cerebral artery occlusion (MCAO) was investigated. Methods. The authors induced permanent, focal cerebral ischemia by using either suture-induced occlusion or direct division of the MCA in Sprague—Dawley rats. Electrical stimulation of the cervical spinal cord was performed during cerebral ischemia. Cerebral blood flow was assessed using both laser Doppler flowmetry (LDF) and quantitative radiotracer analysis. Stroke volumes were analyzed after 6 hours of ischemia. Spinal cord stimulation resulted in a 52.7 ± 13.3% increase in LDF values (nine animals). Following MCAO, LDF values decreased by 64.1 ± 3.6% from baseline values (10 animals). Spinal cord stimulation subsequently increased LDF values to 30.9 ± 13.5% below original baseline values. These findings were corroborated using radiotracer studies. Spinal cord stimulation in the setting of transcranial MCAO significantly reduced stroke volumes as well (from 203 ± 33 mm3 [control] to 32 ± 8 mm3 [MCAO plus SCS], seven animals in each group, p < 0.001). Similarly, after suture-induced MCAO, SCS reduced stroke volumes (from 307 ± 29 mm3 [control] to 78 ± 22 mm3 [MCAO plus SCS], 10 animals in each group, p < 0.001). Conclusions. A strategy of performing SCS for the prevention of critical ischemia is feasible and may have the potential for the treatment and prevention of stroke.

Effects of cervical spinal cord stimulation on cerebral blood flow in the rat

2000 ◽  
Vol 93 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Oren Sagher ◽  
Dah-Luen Huang
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Spinal Cord Stimulation ◽  
Cervical Spinal Cord ◽  
Cervical Cord ◽  
Peripheral Vasculature ◽  
Doppler Flowmetry ◽  
Content Type ◽  
Fine Print

Object. Spinal cord stimulation (SCS) is frequently used for the treatment of chronic pain. Although the mechanisms by which SCS alleviates pain are unclear, they are believed to involve changes within the dorsal horn of the spinal cord. Spinal cord stimulation has also been found to cause significant vasodilation in the peripheral vasculature. The mechanisms underlying this effect are thought to involve sympathetic blockade. A rostral vasodilatory effect has also been described, but changes in cerebral blood flow (CBF) have been poorly delineated. Using laser Doppler flowmetry (LDF), the authors examined the effects of cervical SCS on CBF in rats. Methods. Cervical SCS was found to result in a significant increase in cortical LDF values (83 ± 11% [mean ± standard error of the mean]). The increase in cortical LDF values was not accompanied by a significant increase in systemic blood pressure. Stimulation of the upper cervical spinal cord was more effective in inducing LDF changes than was that of the lower cervical cord. Changes in SDS-induced LDF values were significantly attenuated after spinal cord transection at the cervicomedullary junction and by the administration of the sympathetic blocker hexamethonium. Conclusions. These results indicate that cervical SCS may induce cerebral vasodilation and that this effect may involve indirect effects on vasomotor centers in the brainstem as well as an alteration in sympathetic tone.

Sympathetic mechanisms in cerebral blood flow alterations induced by spinal cord stimulation

2003 ◽  
Vol 99 (4) ◽  
pp. 754-761 ◽  
Author(s):  
Sachin Patel ◽  
Dah-Luen Huang ◽  
Oren Sagher
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Spinal Cord Stimulation ◽  
Sympathetic Tone ◽  
Variable Degree ◽  
Sympathetic Blockade ◽  
Content Type ◽  
Systemic Hypotension ◽  
Fine Print

Object. Cervical spinal cord stimulation (SCS) has been found to augment cerebral blood flow (CBF) in a number of animal models, although the mechanisms underlying the cerebrovascular effects of SCS are poorly described. In this study, the authors examined the role of sympathetic tone in CBF alterations induced by SCS in rats. Methods. Spinal cord stimulation was performed at three intervals while CBF was monitored with laser Doppler flowmetry (LDF). Either hexamethonium (5, 10, or 20 mg/kg), prazosin (0.25, 0.5, or 1 mg/kg), idazoxan (0.5, 1, or 2 mg/kg), propranolol (1, 2, or 4 mg/kg), or vehicle was administered intravenously before the second stimulation. Changes in LDF values due to SCS were recorded as the percentage of change from baseline values and were analyzed. In vehicle-treated animals, SCS increased LDF values by 60.5 ± 1.8% over baseline, whereas both high-dose hexamethonium and prazosin completely abolished the SCS-induced increases in LDF values. On the other hand, LDF values increased by 50.9 ± 4% and 61.4 ± 4% after SCS in the presence of idazoxan or propranolol, respectively. Administration of sympathetic nervous system blockers resulted in a variable degree of systemic hypotension as well. Nevertheless, induced hypotension without sympathetic blockade had only a minimal effect on SCS-induced augmentation of LDF values (48 ± 1.4% over baseline). Conclusions. Sympathetic tone plays a major role in SCS-induced increases in CBF. This effect seems to be mediated primarily by α1-adrenergic receptors. Systemic hypotension alone cannot explain the effects of sympathetic blockade on the SCS response. Clinical use of SCS in the treatment of cerebral ischemia should take α1-adrenergic receptor sympathetic tone into account.

Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia

1989 ◽  
Vol 70 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Toshihiko Kuroiwa ◽  
Makoto Shibutani ◽  
Riki Okeda
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Reactive Hyperemia ◽  
Diffusion Method ◽  
Left Middle Cerebral Artery ◽  
Content Type ◽  
Bbb Opening ◽  
Fine Print

✓ The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia.

Thresholds of focal cerebral ischemia in awake monkeys

1981 ◽  
Vol 54 (6) ◽  
pp. 773-782 ◽  
Author(s):  
Thomas H. Jones ◽  
Richard B. Morawetz ◽  
Robert M. Crowell ◽  
Frank W. Marcoux ◽  
Stuart J. FitzGibbon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neurological Function ◽  
Local Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Fine Print

✓ An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.

The effect of intracarotid infusion of dexamethasone and 5-hydroxytryptamine on cerebral blood flow and metabolism in baboons

1978 ◽  
Vol 48 (4) ◽  
pp. 594-600 ◽  
Author(s):  
A. David Mendelow ◽  
Benjamin H. Eidelman ◽  
Thomas A. McCalden
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Internal Carotid ◽  
Cerebral Oxygen ◽  
Oxygen Utilization ◽  
Content Type ◽  
Baseline Values ◽  
Xenon 133 ◽  
Fine Print ◽  
Clearance Technique

✓ The effect of intracarotid infusion of dexamethasone on cerebral blood flow and cerebral oxygen utilization was measured in baboons using the xenon-133 clearance technique. The cerebrovascular response to intracarotid infusion of 5-hydroxytryptamine (5-HT) was then determined during simultaneous infusion of the steroid. Infusion of dexamethasone alone and infusion with 5-HT produced no significant change in cerebral blood flow or cerebral oxygen utilization when compared to baseline values. The study indicates that neither dexamethasone nor 5-HT with dexamethasone modify cerebral blood flow when infused via the internal carotid artery.

scholarly journals l-Arginine-Induced Regional Cerebral Blood Flow Increase is Abolished after Transient Focal Cerebral Ischemia in the Rat

1997 ◽  
Vol 17 (10) ◽  
pp. 1074-1080 ◽  
Author(s):  
Bernd Sporer ◽  
K. Helge Martens ◽  
Uwe Koedel ◽  
Roman L. Haberl
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Regional Cerebral Blood Flow ◽  
Focal Cerebral Ischemia ◽  
Regional Cerebral Blood ◽  
Doppler Flowmetry ◽  
Transient Focal Cerebral Ischemia ◽  
Reperfusion Period ◽  
Synthase Inhibitor

We investigated the l-arginine-induced, regional cerebral blood flow (rCBF) enhancement after different durations of transient focal cerebral ischemia in the rat to determine if l-arginine increases rCBF after transient focal cerebral ischemia. Focal ischemia (5 minutes and 20 minutes) followed by 90 minutes of reperfusion was induced in a normotensive rat suture-model. Regional cerebral blood flow in both hemispheres was measured by laser-Doppler-flowmetry. Reactivity of rCBF to l-arginine (300 mg/kg) was measured 45 minutes after reperfusion, and hypercapnia 90 minutes after reperfusion. The effect of d-arginine and pretreatment with the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine (l-NA) (10 mg/kg) was examined in additional groups. Hypercapnia and l-arginine increased rCBF in sham operated controls and on the nonischemic hemispheres. d-arginine did not. Twenty-minute long ischemia significantly reduced the response to l-arginine (control side: 115 ± 5.9%; ischemic side: 107 ± 6.1%, n = 7) and hypercapnia, 5 minutes of ischemia did not. Nω-nitro-l-arginine pretreatment partly restored the l-arginine-induced rCBF increase. Thus, rCBF increase caused by l-arginine in the reperfusion period was unaffected by 5 minutes of ischemia, but reduced by 20 minutes of ischemia. The restoration after pretreatment with l-NA may be caused by attenuated production of cytotoxic substances, e.g., NO and related compounds.

Differences in critical cerebral blood flow with age in swine

1991 ◽  
Vol 75 (1) ◽  
pp. 103-107 ◽  
Author(s):  
Jun Harada ◽  
Akira Takaku ◽  
Shunro Endo ◽  
Naoya Kuwayama ◽  
Osamu Fukuda
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Content Type ◽  
Neonatal Pigs ◽  
S 100 ◽  
Newborn Pigs ◽  
Electroencephalogram Eeg ◽  
The Brain ◽  
Fine Print

✓ Normal cerebral blood flow (CBF), critical CBF at a flat reading of the electroencephalogram (EEG), and reversibility of the flat EEG after reperfusion were investigated in a total of 59 pigs, including seven newborns (1 to 3 days of age), 38 juveniles (1 month old), and 14 adults (7 months old). The CBF was determined by the hydrogen clearance method; the EEG was recorded continuously and a power spectrum analysis was performed. Cerebral ischemia was produced by occlusion of both common carotid arteries and induction of hypotension (approximately 50 mm Hg). The flat EEG reversibility was investigated for 3 hours after reperfusion. As parameters of brain development, the neuronal density and the time at which the S-100 protein appeared in the brain were examined. Normal CBF was highest in neonatal pigs and decreased with age. The critical CBF at a flat EEG was lowest in newborn pigs and was elevated with development of the brain. Tolerance against cerebral ischemia was greatest in newborn pigs.

Improvement of limb circulation in peripheral vascular disease using epidural spinal cord stimulation: a prospective study

1997 ◽  
Vol 86 (4) ◽  
pp. 662-669 ◽  
Author(s):  
Krishna Kumar ◽  
Cory Toth ◽  
Rahul K. Nath ◽  
Ashok K. Verma ◽  
John J. Burgess
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Vascular Disease ◽  
Spinal Cord Stimulation ◽  
Long Term Outcome ◽  
Content Type ◽  
Good Outcome ◽  
Peak Blood ◽  
Fine Print

✓ Spinal cord stimulation was used in 46 patients for pain associated with lower extremity ischemic vascular disease that was considered to be nonreconstructable. Thirty-nine patients who had a follow-up examination between 2 and 36 months after the procedure form the basis of this report. Thirty (77%) of 39 cases were considered successful. Clinical endpoints indicating failure included amputation, vascular reconstruction, poor pain relief, or hardware malfunction. The transcutaneous partial pressure of oxygen (TcPO2) increased in both target and control feet. In patients with good outcome with a preimplantation TcPO2 of less than 30 mm Hg, TcPO2 increased significantly (p < 0.05). Pulse volume recording improved significantly (p < 0.05) at the thigh, metatarsal, and great toe levels in successfully treated patients. Peak blood flow velocity also showed a significant increase in patients with good outcome (p < 0.05). Patients with a TcPO2 of less than 10 mm Hg following stimulation tended to undergo amputation within the first 3 months. Improvement in pain control, combined with an increase in TcPO2 values that was greater than 10 mm Hg, were significant early predictors of long-term success. An initial increase in peak blood flow velocities (measured in Doppler studies) of greater than 10 mm also signified a good long-term outcome. Spinal cord stimulation appears to be a useful therapeutic modality for controlling pain and improving perfusion in a select group of patients with end-stage ischemic vascular disease considered nonreconstructable. The best results were seen in patients with severe claudication and rest pain without trophic changes in the foot. The mechanism of this beneficial effect is not yet completely understood.

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