Correlation between somatosensory evoked potentials and neuronal ischemic changes following middle cerebral artery occlusion.

Self Cite

114

Hyperglycemia has been reported to worsen the tolerance of the brain to ischemia, and it has therefore been recommended that patients undergoing neurosurgical procedures not receive glucose-containing solutions. However, whereas most animal studies have used global ischemia models, most neurosurgical procedures are associated with risks of focal rather than global ischemia. We therefore studied the effects of glucose administration in an animal model of focal cerebral ischemia. We anesthetized 20 cats with halothane (0.85% end tidal in oxygen), and a focal cerebral ischemic lesion was produced by clip ligation of the left middle cerebral artery using a transorbital approach. Hyperglycemia (10 cats, mean±SEM plasma glucose concentration 561 ±36 mg/dl) was established before ligation by infusion of 50% glucose in 0.45% saline; the control group (10 cats, mean±SEM plasma glucose concentration 209±28 mg/dl) received 0.45% saline only. Total fluid administered, mean arterial blood pressure, body temperature, and arterial blood gas values did not differ between the two groups 0, 2, and 6 hours after ligation. The cats were killed 6 hours after ligation, and the area of severe ischemic neuronal damage was determined by microscopic examination of a coronal section at the level of the optic chiasm. The mean±SEM area of left cortical severe ischemic neuronal damage was 12±2% of the left cortex in the hyperglycemic group compared with 28±5% in the control group (/><0.01). The area of severe ischemic neurologic damage was inversely related to plasma glucose concentration, for both all cats (r=0.69) and for the control cats alone (r=0.80). We conclude that glucose may protect the brain from severe, focal, ischemic neuronal damage and that further studies are needed to document the efficacy and mechanisms of protection. (Stroke 1989;20:519-523) I n models of global cerebral ischemia, hyperglycemia increases both morphologic brain damage 1 -3 and the severity of neurologic deficits. 4 -3 In these models, temporary global cerebral ischemia is produced by a variety of techniques (including hypoxia, hemorrhage, tourniquet interruption of cerebral blood flow, surgical occlusion of the cerebral vessels, induced hypotension, and cardiac arrest), often in combination, followed by restoration of normal cerebral oxygenation and cir- Received July 13, 1988; accepted September 8, 1988. culation. However, the generalizability of these models to clinical practice is debatable since cerebral ischemia in humans is often focal rather than global. Interventions may have different effects in focal compared with global cerebral ischemia. For example, the administration of barbiturates before ischemia appears to provide protection from focal cerebral ischemia 67 but is ineffective in global ischemia. 8 The effect of hyperglycemia on focal cerebral ischemia remains controversial. Several studies suggest that hyperglycemia worsens the injury, 9 -" whereas others suggest that it either decreases 1213 or has no effect on 14 the extent of cerebral ...

Section: Relation Of Area Of Severe Ischemic Neuronal Damage (Sind) (mentioning

confidence: 94%

Hyperglycemia decreases acute neuronal ischemic changes after middle cerebral artery occlusion in cats.

Zasslow

Pearl

Shuer

et al. 1989

Self Cite

114

“…19 SEP amplitudes were then expressed as a percentage of the initial (pretreatment) amplitude for purposes of statistical analysis. Latencies of the major positive and major negative deflections were determined.…”

Section: Methodsmentioning

confidence: 99%

Dextromethorphan protects against cerebral injury following transient focal ischemia in rabbits.

Steinberg

George

DeLaPaz

et al. 1988

Self Cite

107

We investigated dextromethorphan, both a dextrorotatory opioid derivative and a clinically tested N-methyl-D-aspartate (NMDA) receptor antagonist, in a rabbit model of transient focal cerebral ischemia. Fourteen rabbits were randomly assigned to treatment with a 20 mg/kg i.v. loading dose followed by a 10 mg/kg/hr infusion of 0.4% dextromethorphan in normal saline or with an equivalent volume of normal saline alone. One hour after treatment, the rabbits underwent a 1-hour occlusion of the left internal carotid and anterior cerebral arteries followed by 4 hours of reperfusion. The seven dextromethorphan-treated rabbits showed a significant decrease in the area of neocortical severe ischemic neuronal damage (10.5%) compared with the seven normal saline-treated controls (49.6%, p<0.001). The dextromethorphan-treated rabbits also demonstrated significantly smaller areas of cortical edema (10.2%) on magnetic resonance imaging than the controls (38.6%, p<0.01). Analysis of somatosensory evoked potentials revealed recovery of the ipsilateral amplitude to contralateral values within 5 minutes of reperfusion in the dextromethorphan-treated rabbits but not in the controls (p<0.01). In our rabbit model of transient focal cerebral ischemia, dextromethorphan appears to protect the brain against ischemic neuronal damage and edema, as well as to promote neurophysiologic recovery. This clinically available drug should be further investigated as having potential therapeutic value in the treatment of stroke.

“…After MRI, the brains were prepared for histopathology as described. 16 21 was assessed in the left neocortex and striatum. These microscopic observations were delineated on an enlarged transparency of the slide.…”

Section: -18mentioning

confidence: 99%

Protective effect of N-methyl-D-aspartate antagonists after focal cerebral ischemia in rabbits.

Steinberg

Saleh

Kunis

et al. 1989

Self Cite

We studied the efficacy of postischemic, systemic treatment with the A'-methyl-D-aspartate (NMDA) receptor antagonists dextromethorphan and dextrorphan in a rabbit model of transient focal cerebral ischemia. Twenty-two rabbits underwent 1-hour occlusion of the left internal carotid and anterior cerebral arteries followed by 4.5 hours of reperfusion before sacrifice. One hour after the onset of ischemia, immediately after removing the arterial clips, the rabbits were blindly assigned to treatment with dextromethorphan (20 mg/kg i.v. loading dose followed by 10 mg/kg/hr maintenance infusion, n=7), dextrorphan (15 mg/kg i.v. loading dose followed by 15 mg/kg/hr maintenance infusion, n=7), or an equivalent volume of normal saline alone (ra=8). The maintenance infusion of drugs or saline was continued for the duration of the experiment. The formalin-fixed brains were analyzed with magnetic resonance imaging using coronal T2 -weighted images, and ischemic neuronal damage was assessed on standard coronal hematoxylin-and-eosin-stained sections. The area of neocortical ischemic neuronal damage was significantly reduced in the groups treated with dextromethorphan (4.2%, p<0.0l) and dextrorphan (6.1%,/?<0.01) compared with the controls (36.2%). Magnetic resonance imaging demonstrated significantly smaller areas of cortical edema in the groups treated with dextromethorphan (14.6%, p< 0.01) and dextrorphan (8.0%, p< 0.01) compared with the controls (32.9%). These clinically tested antitussives with NMDA-antagonist properties may have therapeutic value in the treatment of human cerebrovascular disease. (Stroke 1989;20:1247-1252 T he excitatory amino acid glutamate has direct neurotoxic effects and may mediate hypoxic or ischemic neuronal damage. 1 Recent evidence suggests that selective antagonism of the Af-methyl-D-aspartate (NMDA) subclass of excitatory amino acid receptors can reduce such hypoxicischemic neuronal injury in culture, in brain slices, and in animal models.1 -11 Since the competitive NMDA antagonists do not easily penetrate the blood-brain barrier, interest has focused on non- Received December 27, 1988; accepted March 20, 1989. competitive NMDA antagonists such as ketamine, phencyclidine, and MK801. Obviously, a pharmacologic treatment that protects against cerebral damage when administered in a delayed fashion following the ischemic insult would have greater therapeutic potential for clinical stroke. Therefore, we examined the effect of postischemic treatment using DM and DX in our rabbit model. We have reported some of these results in abstract form. 19 Materials and MethodsOur methods have been described. 16 -18 Twentytwo male rabbits weighing 2.5-3.5 kg were anesthetized with 3% halothane delivered by mask. After