Effect of Dexamethasone on the Early Edema Following Occlusion of the Middle Cerebral Artery in Cats

Background and Purpose Recent studies reveal success in treating spinal cord trauma with early, high-dose methylprednisolone. As in spinal cord research, failure to find therapeutic effects with steroids in studies of acute stroke treatment may reflect institution of treatment too late and at too low dosage. We presently test the efficacy of stroke treatment with methylprednisolone administered early and at high doses using a cat temporary middle cerebral artery occlusion model.Methods We occluded the middle cerebral artery for 4 hours in 24 pentobarbital-anesthetized cats. To enhance the probability of brain injury, we maintained the cats' serum glucose concentrations at high levels both during occlusion and for 6 hours afterward. Using a blinded, randomized study design, we treated 12 cats with methylprednisolone (30 mg/kg IV infused over 15 minutes starting 30 minutes after occlusion followed by 5.4 mg • kg"' • h" 1 IV for the next 23 hours) and 12 control cats with vehicle. During and for 8 hours after occlusion, we monitored cerebral blood flow, brain and rectal temperatures, and multiple cardiovascular and blood compositional parameters. We assessed brain pathological outcome

Section: Discussionmentioning

confidence: 99%

Efficacious experimental stroke treatment with high-dose methylprednisolone.

Courten-Myers

Kleinholz

Wagner

et al. 1994

“…Swelling of perivascular glial cells begins within minutes of the onset of ischemia 20 and by 30 minutes, focal edema of cerebral tissue is measurable by change in water content. 15 Investigators find that water content in the cortex in the occluded area is increased 30 minutes after the occlusion, is within normal limits at 60 minutes, and again is increased significantly at 120 and 240 minutes. In the underlying white matter, increased water content is seen at 30, 60, 120, and 240 minutes.…”

Section: Occlusion Of the Middle Cerebral Artery (Mca)mentioning

confidence: 99%

“…Thus, not all the fluid taken up is in equilibrium with plasma and CSF and the tissue as a whole has lost more cation than it has gained. Also in the cat, 120 minutes of focal ischemia induced by occlusion of MCA 15 results in an increase of sodium of 69 mEq/kg dry weight in cerebral cortex of the affected area, while the loss of potassium is 88 mEq/kg. Blood flow is still about 40% of normal in Bartko's MCA occlusion experiments.…”

Section: Changes In Sodium and Potassium Content Of Brain Tissue Assomentioning

confidence: 99%

Report of Joint Committee for Stroke Resources. IV. Brain edema in stroke.

Katzman¹,

Clasen²,

Klatzo³

et al. 1977

209

SUMMARY A classification of brain edema is provided as well as an extensive review of the animal models from which we have derived most of the basic information we have about the formation and resolution of edema. The clinical aspects of cerebral edema in stroke are discussed and also modern methods for identifying cerebral edema in the human. Attention is given to computed tomography and enhanced CT and advances in their application to this condition.Treatment of cerebral edema in the stroke patient using glycerol, dextran 40, mannitol, steroids, and other drugs is discussed and the need pointed out for controlled clinical trials of the therapeutic effectiveness of these agents.THE IMPORTANCE of brain swelling in the pathogenesis of stroke assumes growing significance as physicians increase their understanding of cerebrovascular diseases and their attempts to provide treatment. For example, a recent report 1 shows that in 32 of 100 patients who died as the result of cerebral infarction, transtentorial herniation was considered to be the most serious factor contributing to death. In the experience of most clinicians, a "swollen brain" can be demonstrated as well in a substantial number of patients who come to autopsy as a result of cerebral hemorrhage.The study group members appreciate fully the difficulties involved in understanding and interpreting current knowledge of cerebral edema pathogenesis gained from animal experimentation. Nevertheless, the basic information derived from a variety of animal models and reported in detail in the first pages of this report is considered essential to understanding the cerebrovascular events occurring in man. The ultimate objectives are to prevent cerebral edema wherever possible and to treat the condition when it develops, with the expectation of reducing the morbidity and mortality resulting from this complication. Classification of Cerebral EdemaCerebral edema is defined as an increase in brain tissue volume resulting from an increase in its fluid content.2 It must at all times be differentiated from brain engorgement caused by an increase in the volume of blood within a region of the brain 3 and from brain swelling due to intracerebral hemorrhage.• A priori, one might suppose that edema associated with cerebrovascular lesions would be primarily of the vasogenic type, since both overt injury to blood vessels and often a discrete focal brain lesion are present. However, experimentally, the increase in tissue volume and water is found usually to reach a peak prior to the extravasation of protein or of BBB indicators. Clinically, swelling in and around an area of infarction may be present before the radionuclide (RN) scan used to monitor BBB leakage becomes positive. This evidence suggests that brain edema due to focal ischemia begins as a cytotoxic type and is followed by a vasogenic edema. But the pathophysiology of this edema and its pattern of development are sufficiently specific to warrant a separate classification as ischemic brain edema. Biochemical Measures of Exp...

“…11 All have suppressed infarction in the laboratory, but few have been of value in managing patients with acute cerebral artery occlusion.…”

Section: Introductionmentioning

confidence: 99%

Barbiturate Protection From Cerebral Infarction in Primates

Hoff

Smith

Hankinson

et al. 1975

207

Barbiturate Protection From Cerebral Infarction in Primates• Baboons were anesthetized with halothane or pentobarbital prior to middle cerebral artery (MCA) occlusion to test the protective effect of barbiturates against stroke in primates. Significantly less infarction was found in animals that received 90 mg per kilogram pentobarbital or more than occurred in control animals. Because of cardiovascular and ventilatory complications at high doses of barbiturate, however, therapeutic trials to suppress stroke in the human must await further identification of an effective regimen which includes a safe barbiturate dose.