Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.

125

Steroids reduce permeability of the blood-brain barrier and inhibit active sodium transport by brain capillaries in vitro. Since the rate of edema formation during the early stages of ischemia is related to the rate of sodium transport from blood to brain, this study was designed to determine whether steroids reduce ischemic edema formation by inhibiting blood-brain barrier sodium transport. Dexamethasone was compared with progesterone since the latter is a more potent inhibitor of sodium transport in isolated capillaries. Sprague-Dawley rats were treated with vehicle (n=22) or 2 mg/kg of either dexamethasone (n=22) or progesterone (n=17) 1 hour before occlusion of the middle cerebral artery. After 4 hours of ischemia, brain water content and blood-brain barrier permeability to [ 3 H]«-aminoisobutyric acid and sodium-22 were determined. In controls, mean±SEM water content of tissue in the center of the ischemic zone was 82.4 ±0.2%. Brain edema was significantly reduced following pretreatment with either dexamethasone (80.6±0.1%,p<0.001) or progesterone (81.5±0.3%, p<0.05). There was also a significant reduction in blood-brain barrier permeability to a-aminoisobutyric acid in normal brain following either treatment (e.g., 2.21 ±0.19 and 1.37±0.10 /il/g/min,/><0.001, for control and dexamethasone treatments, respectively), but no effect on the permeability to sodium (e.g., 1.19±0.05 and 1.12±0.11 /il/g/min for control and dexamethasone treatments, respectively). Furthermore, steroid treatment did not reduce blood-brain barrier permeability to sodium in ischemic brain (e.g., 2.53 ±0.39 and 2.40±0.33 /il/g/min for control and dexamethasone treatments, respectively). We conclude that pretreatment with dexamethasone and, to a lesser extent, progesterone reduces brain edema during the early stages of ischemia; however, this effect is not the result of reduced blood-to-brain sodium transport. (Stroke 1990;21:1199-1204)

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Effect of steroids on edema and sodium uptake of the brain during focal ischemia in rats.

Betz

Coester

1990

125

“…Following the final intracisternal injection of endothelin, follow-up angiograms were taken for up to 2 hours. Basilar artery caliber was measured on the angiograms at three points: close to the vertebrobasilar junction (Di), at the midpoint between the vertebrobasilar junction and the basilar tip (D 2 Similar experiments were performed in five adult mongrel dogs weighing approximately 10 kg to investigate the effect of endothelin for up to 12 hours. The procedure in dogs was exactly the same as that in cats, except the amounts of endothelin were doubled; for intra-arterial infusion, 6-6,000 pmol in 6 ml buffered saline was given over 2 minutes and for intracisternal injection, 1-1,000 pmol in 1 ml buffered saline was given.…”

Section: Methodsmentioning

confidence: 99%

Endothelin acts in feline and canine cerebral arteries from the adventitial side.

Mima

Yanagisawa

Shigeno

et al. 1989

Self Cite

129

We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73±4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. T he endothelium of cerebral blood vessels is now recognized not only as a physical barrier isolating the brain from the environment but also as an organ having a number of important active functions. 1 -2 Both cerebral and peripheral endothelium are known to produce different classes of diffusible vasoactive factors in response to a variety of stimuli, thereby regulating vascular smooth muscle tonus.3 Endothelin is a vasoconstrictor peptide that we recently characterized from the supernatant of cultured porcine aortic endothelial cells. 4 Consisting of 21 amino acid residues with two intrachain disulfide bonds, endothelin is one of the most potent vasoconstrictors known. Endothelin-induced constriction of cerebral and peripheral arteries from various species in vitro is extremely long-lasting and is characteristically dif- Received May 17, 1989; accepted July 5, 1989. ficult to wash out. In vivo, an intravenous bolus injection of endothelin to anesthetized, conscious rats causes a sustained increase in arterial blood pressure that lasts for >1 hour. Cloning and sequence analysis of endothelin complementary deoxyribonucleic acid from porcine and human endothelial cells has demonstrated that endothelin is produced from an approximately 200-residue prepro-type precursor much like other peptide hormones and that human and mature porcine endothelin are identical. 5 The level of preproendothelin messenger ribonucleic acid (mRNA) in endothelial cells is influenced by various chemical and mechanical stimuli, suggesting the importance of endothelin in the local control of vascular tonus.We are interested in the possible involvement of endothelin in the local regulation of cerebral arteries in vivo. It is of special interest to assume that production of excess endothelin contributes to the development of delayed vasospasm after subarachnoid hemorrhage. We investigated the response of feline and canine basilar artery in vivo to the intra-arterial and intracisternal administration of endothelin.

“…6 See Editorial Comment, p 1336 A decrease in Na,K-ATPase activity has been reported during ischemia, but the results of in vivo studies have varied. 7 - 8 Depletion of ATP precedes reduction of Na,K-ATPase activity in brain tissue affected by transient global ischemia, but it has not been proven that this ATP depletion is the primary factor causing the decreased enzyme function. 9 Furthermore, Na,K-ATPase activity after regional ischemia followed by reperfusion has not been investigated.…”

mentioning

confidence: 99%

Edema, cation content, and ATPase activity after middle cerebral artery occlusion in rats.

Yang

Chen

Kinouchi

et al. 1992

Background and Purpose: Reduction of cerebral blood flow results in several acute metabolic disturbances, including a reduction in Na,K-ATPase activity. The relation between this reduction and the onset of edema is unknown, as is the effect of restoration of blood flow. Therefore, we investigated the role of decreased Na,K-ATPase activity in the pathogenesis and time course of ischemic brain edema and reperfusion.Methods: The middle cerebral arteries of rats were occluded by cannulation with a nylon suture for 30, 60, 120, or 240 minutes. The animals were then decapitated (permanent occlusion) or the suture was withdrawn to allow 24 hours of reperfusion before decapitation (temporary occlusion). Na,K-ATPase activity and Na + , K + and water contents were measured at various intervals. Results: In the ischemic hemisphere, Na,K-ATPase activity was significantly decreased at 30, 60,120, and 240 minutes of permanent occlusion (p<0.05). There was also a significant decrease in rats subjected to 60 or 120 minutes of temporary occlusion followed by 24 hours of reperfusion. Water content increased after 60, 120, or 240 minutes of permanent occlusion (p<0.01); after 24 hours of reperfusion, water content remained elevated (p<0.01). The Na + content increased after both permanent and temporary occlusion, and the K + content decreased only after permanent occlusion. Increases in water content correlated with decreases in Na,K-ATPase activity after temporary occlusion and with the Na + : K + ratio after permanent occlusion.Conclusion: Reduction in Na,K-ATPase activity resulting in disruption of cellular ionic homeostasis may account for early development of cytotoxic brain edema after permanent occlusion of the middle cerebral artery. Such edema is also present 24 hours after 60 and 120 but not 30 minutes of temporary occlusion. -2 which may be exacerbated rather than reversed even if ischemia is followed by reperfusion.3 The temporal sequence of these disturbances is not precisely known; however, interruption of cerebral blood flow is generally believed to result first in depletion of energy stores and next in disruption of ion homeostasis, release of neurotransmitter amino acids, and release of free fatty acids. 4 These physiological and biochemical alterations are the primary determinants of cell survival or death.Decreased energy metabolism results in dysfunction of all adenosine triphosphate (ATP)-dependent enzymes. One such enzyme is Na,K-ATPase, a catalyst for the Na + pump, which normally maintains intracellularFrom the Departments of Neurological Surgery