The effect of repeated occlusions of the middle cerebral artery on pial arterial behavior and cerebral structure

Temporary clipping of the major arterial trunk is a very important maneuver to control excessive unexpected bleeding during a neurosurgical operation, but repeated temporary clippings sometimes give rise to severe neurological deficits after surgery. In clinical practice, a major stroke can occur after many transient ischemic attacks without distinct angiographic occlusion. To confirm and explain these clinical experiences, the present study was performed. First, 20-min, 30-min and 1-h occlusion of the middle cerebral artery was performed in each of 5 cats, and pial arterial behavior, cerebral edema and infarction were observed. In the 20-min occlusion group, no abnormal change was found 5 hours after recirculation. In the 30-min occlusion group, cerebral edema was present in 10.5 +/- 4.2% of the hemisphere, but no infarction was observed, and pial arterial caliber remained in a 10% dilated state throughout the experimental periods. In the 1-h occlusion group, cerebral edema was present in 41.2 +/- 7.5% of the hemisphere and infarction was found in 34.5 +/- 9.5%. Pial arteries returned to a 20% dilated state but redilated by 45% at the end of experiment. As the second experiment, three 20-min occlusions at 1-h interval and two 30-min occlusions at 1-h interval were performed in each 10 cats. Pial arteries had dilated by 40% after release of the last occlusion in both groups. The extent of cerebral edema was 19.5 +/- 8.1% of hemisphere in the 20-min occlusions group and 36.6 +/- 9.7% in the 30 min occlusions group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of calcium antagonist nimodipine and induced hypertension on cerebral vessel reactivities, cerebral blood flow, cerebral edema and infarction in cats with one hour middle-cerebral-artery occlusion

Treatment with the calcium entry blocker nimodipine is recommended as effective therapy for cerebral ischemia due to cerebral vasospasm or cerebral thrombosis. On the other hand, treatment with induced hypertension is a widely accepted measure to reverse ischemic deficits caused by vasospasm. Thus, a combination of the two regimens--nimodipine and induced hypertension--may have real benefits for cerebral ischemia. But it is possible that the benefit of one is abolished by adverse effects of the other, or that a combination of both may not be as effective as the use of only one therapy. In order to investigate these problems, the effects of nimodipine and induced hypertension on cerebral vessel, cerebral blood flow, cerebral edema and cerebral infarction using a one hour middle-cerebral-artery occlusion model in cats. Twenty-one anesthetized cats were divided into a control group, the nimodipine-treated group, and the nimodipine-and-induced-hypertension group. There were seven cats in each group. Occlusion of the middle cerebral artery (MCA) was continued for one hour in each animal. Induced hypertension was a little higher than resting values, and it was continued for only one hour during MCA occlusion, brought on by instillation of dopamine. Cerebral pial arteries dilated much more prominently during and after the occlusion of MCA in the nimodipine-and-induced-hypertension group than other groups. Although cerebral blood flow in the nimodipine group, and the nimodipine-and-induced-hypertension group increased more in the non-ischemic hemisphere, the most remarkable increase was seen around the infarcted cortex in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preservation of neuronal function during prolonged focal cerebral ischemia by ventriculocisternal perfusion with oxygenated fluorocarbon emulsion

The left middle cerebral artery and both carotid arteries of 17 cats were occluded to evaluate the effects of oxygenated fluorocarbon emulsion on brain ischemia. Carotid and middle cerebral arteries were occluded concurrently for 2 hours, followed by occlusion of the middle cerebral artery only for another 24 hours. Six animals were treated with oxygenated fluorocarbon emulsion delivered by ventriculocisternal perfusion, 5 received ventriculocisternal perfusion with mock cerebrospinal fluid, and 6 were untreated. Perfusions were started 3 hours after the initial ischemic insult. Infarct size judged by tetrazolium staining and standard neuropathological stains was significantly smaller in the treated animals. The mechanism of protection is as yet unknown, but most likely reflects oxygen/nutrient diffusion into the ischemic middle cerebral artery zone from the ventricular fluorocarbon, or removal of harmful metabolites. The results imply that ventriculocisternal perfusion with fluorocarbon emulsion can preserve neuronal function during a major cerebral vessel occlusion. In the cat, therapy is effective if begun within 3 hours after ischemia starts.     

Effects of repeated temporary clipping of the middle cerebral artery on pial arterial diameter, regional cerebral blood flow, and brain structure in cats

Temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations; however, repeated temporary clipping can give rise to severe neurological deficits after surgery. The present study was performed to confirm and explain these clinical findings. Initially, a single 20-minute or 1-hour occlusion of the middle cerebral artery was performed in each of 5 cats. Pial arterial diameter was determined by video imaging, regional cerebral blood flow was measured by autoradiography, and cerebral edema and infarction were observed. In the 20-minute occlusion group, no abnormal changes were found 5 hours after recirculation. In the 1-hour occlusion group, pial arteries were dilated by 45%, and regional cerebral blood flow increased to more than twice the resting cortical values. The extent of cerebral edema was 41.2 +/- 7.5% (SE) and infarction was 34.5 +/- 9.5% (SE) of the hemisphere. In the second experiment, three 20-minute occlusions of the middle cerebral artery in a 1-hour interval were performed in 20 cats. In 10 of them, thiopental (40 mg/kg) was used to protect the brain. In the group without barbiturate treatment, pial arteries were dilated by 40% at the end of experiment, regional cerebral blood flow decreased to about 70% compared with single 20-minute occlusion, cerebral edema was 19.5 +/- 8.1% (SE), and infarction was 8.1 +/- 3.7% (SE) of the hemisphere. In the treated group, these were only trivial changes. The effect of repeated clipping may cumulatively cause brain damage, and barbiturates should be used whenever repeated clipping is necessary.     

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

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.     

小鼠局灶性脑缺血的脑血流动力学和脑损害的评价

目的　建立一种可靠的小鼠脑缺血模型,了解永久性和暂时性阻断血管后的脑病理生理变化。方法　 Ｃ Ｄ１ 小鼠,单侧大脑中动脉线栓阻断,监测脑血流,测量梗塞体积和血脑屏障破坏程度。结果　小鼠均出现成熟缺血核心区和半暗区。不同缺血／ 再灌注时间产生不同缺血损害和血脑屏障破坏,但有时限。结论　建立了一种可靠、复制性强的小鼠局灶性缺血模型。血脑屏障破坏在缺血损害中起重要作用。短时间缺血后的再灌注能减轻缺血性脑损害。     

The influence of the calcium antagonist nimodipine and induced hypertension on the behavior of the cerebral pial arteries, the blood-brain barrier, cerebral edema, and cerebral infarction in cats with one-hour occlusion of the middle cerebral artery

Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each: nimodipine treatment, nimodipine treatment combined with induced hypertension, or a control group. The behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window. The middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach. Five hours after circulation was reestablished in the middle cerebral artery, Evans blue dye was injected intravenously: 30 minutes later, the animal was killed. Administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment. Induced hypertension was produced by administration of dopamine during the occlusion. Damage to the blood-brain barrier (BBB) was judged by extravasation of Evans blue dye. Cerebral edema and infarction were evaluated from histological findings. They were most prominent in the control group: the extent of hemisphere affected was as follows (mean +/- standard error): extravasation, 40.5 +/- 8.8%; edema, 43.2 +/- 5.7%; infarction, 35.5 +/- 9.6%. On the other hand, the extravasation of Evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension (extravasation, 28.2 +/- 9.6% of the hemisphere; edema, 30.3 +/- 7.1%) than in the group treated with nimodipine alone (extravasation, 18.5 +/- 8.7% of the hemisphere; edema, 19.4 +/- 6.3%), but the infarction size was similar in both groups (16.6 +/- 4.9% of the hemisphere in the former; 17.0 +/- 6.2 in the latter).(ABSTRACT TRUNCATED AT 250 WORDS)     

Discrepancies among CT, histological, and blood-brain barrier findings in early cerebral ischemia

The development of ischemic edema and blood-brain barrier (BBB) disruption during the 1st day of experimental cerebral infarction induced by transorbital occlusion of the middle cerebral artery (MCA) in cats was evaluated by computerized tomography (CT) scanning and compared to gravimetric and pathological studies. Regional cerebral blood flow was measured using the hydrogen clearance technique or stable xenon-enhanced CT scanning. Edema was observed gravimetrically and microscopically as early as 1 hour after the onset of ischemia in the cortex and at 3 hours or later in both the cortex and white matter. However, a significant decrease of Hounsfield numbers on the CT scans was not detectable at 1 or 3 hours and was scarcely visible at 9 hours after occlusion. Disruption of the BBB was detected by leakage of Evans blue dye at 3 hours after the occlusion in two of six animals and at 9 hours in five of five animals. However, CT scanning after infusion of contrast material showed no significant increase in Hounsfield number even 24 hours after MCA occlusion. These discrepancies should be emphasized when the dynamics of ischemic edema and BBB disruption are evaluated for clinical therapy by CT scanning.     

The effect of neodymium yttrium aluminum garment laser on the cerebral blood vessel and blood brain barrier

The effect of the laser energy to the cerebral vascular reactivity and the blood brain barrier. A Nd:YAG laser with 20 watt impacts of 0.5, 1.0, 2.5 and 5.0 seconds duration time were irradiated through the cranial window made at the parietal regions of anesthetized adult cats. The disruption of the blood brain barrier was examined by checking the degree of the extravasation of Evans blue dye administrated in the vein. The cortical vessel reactivity was observed through the cranial window and evaluated using an intravital microscope and a videoangiometer. The extravasation of Evans blue dye was seen uniformly extending from the histologically changed area into the surrounding tissue in all experiments. The extent of the extravasation of dye was 1 to 1.5 mm larger than the extent of the histologically changed area produced by laser irradiation. Pial arteries in the area with histological changes dilated markedly and some of them lost their blood stream. Pial arteries in the area of Evans blue extravasation, but outside it histological changes also dilated markedly. Furthermore, pial arteries within a distance of 200 to 400 microns from the edge of the Evans blue extravasation area also dilated moderately. A statistical estimation showed that the degree of dilatation of arteries in the area outside the histological change improved significantly in the time course of five minutes.     

Catecholamine content of cerebral tissue after occlusion or manipulation of middle cerebral artery in cats.

The authors determined by fluorimetry the norepinephrine-epinephrine content (NE-E) of cerebral tissue from 38 cats, to ascertain whether constriction of hypersensitive arterial vessels by vasoactive agents in ischemic cerebral tissue could cause extension of cerebral infarcts and worsening of neurological deficits. Twenty-three cats had the left middle cerebral artery (MCA) occluded transorbitally, and 10 cats had sham operations. Five cats had only the surgical procedures necessary for obtaining tissue; mean NE-E content was 0.30 mug/gm (SD=0.041). For the other 33 cats, including those with sham operations, values were variable, ranging from 0.07 to 0.60 mug/gm. Low values usually were obtained for ischemic hemispheres 24 hours and 7 days after MCA occlusion, but at other times values could be high or low on either side. Many factors unrelated to tissue damage, including arterial manipulation, influence the catecholamine content of cerebral tissue.     

Treatment of acute focal cerebral ischemia with intermittent, low dose mannitol

The object of this investigation was to study the effects of intermittent, low dose mannitol therapy on conscious cats after acute left middle cerebral artery (MCA) occlusion. A simple implanted device was applied to the proximal left MCA of 40 adult cats using microsurgical techniques. In the acute experiments, 10 cats were untreated and 10 cats received mannitol (0.5 g/kg intravenously) immediately before occlusion and again 3, 6, and 9 hours later. They subsequently underwent intra-arterial perfusion with colloidal carbon and buffered paraformaldehyde 12 hours after occlusion. The plasma osmolality immediately before perfusion was 316 +/-2 (SD) milliosmoles in untreated cats and 331 +/- 5 milliosmoles in treated cats. Gross swelling, impaired carbon filling, and breakdown of the blood-brain barrier (BBB) to fluorescein were seen in the left MCA territory of 8 untreated cats and 1 treated cat. The mean percentage of gray matter cross sectional area where severe ischemic neuronal alterations predominated was 45 +/- 12% in untreated and 14 +/- 16% in treated cats (p less than 0.01). The mean capillary luminal diameter in the left sylvian cortex was 4.5 +/- 1.0 mu in untreated cats (control, 6.5 +/- 1.0 mu) and 5.5 +/- 1.0 mu in treated cats. In the subacute experiments, 10 cats were not treated and 10 cats received mannitol as in the acute experiments. The cats were killed with a large bolus of sodium pentobarbital 48 hours after left MCA occlusion. Gross swelling and breakdown of the BBB were less severe in treated cats. The mean cross sectional area of infarcted tissue was 55 +/- 12% in untreated cats and 33 +/- 21% in treated cats (p less than 1.0). The findings of this study indicate that intermittent, low dose mannitol therapy delays the onset of ischemic cerebral injury and may reduce the size of the eventual infarct or convert a potential infarct into a so-call "transient ischemic attack." (Neurosurgery, 5: 684--691, 1979).     

A new rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations

OBJECT: A new experimental model of chronic cerebral hypoperfusion was developed to study the effects of systemic arterial shunting and obstruction of the primary vessel that drains intracranial venous blood on cerebral perfusion pressure (CPP), as well as cerebral pathological changes during restoration of normal perfusion pressure. METHODS: Twenty-four Sprague-Dawley rats were randomly assigned to either a sham-operated group, an arteriovenous fistula (AVF) group, or a model group (eight rats each). The animal model was readied by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein (EJV) and the ipsilateral common carotid artery (CCA), followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Systemic mean arterial pressure (MAP), draining vein pressure (DVP), and CPP were monitored and compared among the three groups preoperatively, immediately postoperatively, and again 90 days later. Following occlusion of the fistula after a 90-day interval, blood-brain barrier (BBB) disruption and water content in the right cortical tissues of the middle cerebral artery territory were confirmed and also quantified with transmission electron microscopy. Formation of a fistula resulted in significant decreases in MAP and CPP, and a significant increase in DVP in the AVF and model groups. Ninety days later, there were still significant increases in DVP and decreases in CPP in the model group compared with the other groups (p < 0.05). Damage to the BBB and brain edema were noted in animals in the model group during restoration of normal perfusion pressure by occlusion of the fistula. Electron microscopy studies revealed cerebral vasogenic edema and/or hemorrhage in various amounts, which correlated with absent astrocytic foot processes surrounding some cerebral capillaries. CONCLUSIONS: The results demonstrated that an end-to-side anastomosis between the distal EJV and CCA can induce a decrease in CPP, whereas a further chronic state of cerebral hypoperfusion may be caused by venous outflow restriction, which is associated with perfusion pressure breakthrough. This animal model conforms to the basic hemodynamic characteristics of human cerebral arteriovenous malformations.     

Cerebral arteriovenous malformations, steal, and the hypertensive breakthrough threshold. An experimental study in rats

An experiment was designed to investigate the effects of arteriovenous (AV) fistula occlusion on cerebral autoregulation. A right carotid-jugular fistula was created in 63 rats in such a way as to produce an intracranial AV fistula with a loop extension into the neck. The fistula was occluded after an 8-week interval with the rats under both normotension and metaraminol-induced hypertension, and evidence of blood-brain barrier disruption was investigated with an Evans blue dye technique. The results indicate that an intracranial AV fistula may cause cerebral steal which is responsible for a reduction in the threshold for hypertensive breakthrough following fistula occlusion.     

Haemodynamic changes in the cerebral circulation of the cat during occlusion of the middle cerebral artery

Summary In a group of 21 cats, the middle cerebral artery pressure (MCAP) was recorded by means of a catheter introduced into the artery at its origin, just distal to the occlusion. The effects of hypertension, hypercapnia, and hypocapnia were studied.In a group of five cats, both middle cerebral arteries (MCA) were catheterized and the pressure was recorded simultaneously on both sides.In another group of five cats, O₂ tension measurements were made with the aid of oxygen electrodes in the brain tissue, the occluded MCA, and the common carotid artery.Some of the results obtained in this study are compared with the results of a previous study where monkeys were used as experimental animals.C. A. F. Tulleken is neurosurgeon at the Ursula Kliniek and staff member of the TNO-GO Workgroup in Clinical Neurophysiology, both at Wassenaar.     

Adult pial arteriovenous fistula and superior sagittal sinus stenosis: angiographic evidence for high-flow venopathy at an atypical location. Case report

The authors present the case of a 69-year-old man who suffered from bilateral cortical venous hypertension due to a brain pial arteriovenous malformation (AVM) with a high-flow fistula. The AVM became complicated by the development of a high-grade stenosis of the posterior superior sagittal sinus (SSS). A comparison of cerebral angiograms obtained at different times revealed that the severe SSS stenosis had developed within a 5-year period and was located distal to the nidus of the left parietal AVM nidus, away from the entrance of the dominant superior superficial cortical draining vein into the SSS. The high-flow fistula was occluded with detachable coils and the AVM nidus was further embolized with acrylic. The SSS stenosis was mechanically dilated by means of balloon angioplasty and stent placement. This case provides angiographic evidence to support the hypothesis that a pial arteriovenous fistula in an adult can cause high-flow occlusive venopathy in a major sinus within a relatively short time and that this acquired high-flow occlusive venopathy can develop at an atypical location distant from the nidus of the AVM.     

Phosphorus-31 magnetic resonance spectroscopy of cerebral ischemia in cats

The energy metabolism of the brain was measured in three types of ischemic models in the cat using phosphorus-31 magnetic resonance spectroscopy. The cerebral ischemia was produced as follows. In Group 1, two balloons were inflated in the left subclavian artery and the brachiocephalic trunk. In Group 2, the left middle cerebral artery was occluded through a transorbital approach. A combination of the two was employed in Group 3. Phosphorus-31 magnetic resonance spectra were obtained serially during 2 hours of ischemia. Immediately after occlusion, peaks of phosphocreatine and adenosine triphosphate decreased, whereas the peak of inorganic phosphate increased and split in two. Intracellular pH determined by chemical shift of the inorganic phosphate peak decreased. These changes were more pronounced in Group 3 when compared with the other groups. Histological study showed no infarction in Group 1 and infarcted areas in Groups 2 and 3. The size of the infarcted area in Group 3 was larger than that in Group 2. These results suggest that the model of middle cerebral artery occlusion potentiated with the occlusion of the brachiocephalic trunk and the left subclavian artery by balloon catheters is a reliable stroke model and that phosphorus-31 magnetic resonance spectroscopy is useful to understand the pathophysiological state of cerebral ischemia in vivo.     

A case of pial single-channel cerebral arteriovenous fistula

A 60-year-old man presented with dizziness, dysarthria, and right hemifacial palsy with sudden onset. Computed tomography scan revealed a small cerebellar hematoma near the left flocculus. Since the site of the hemorrhage was atypical for cerebellar hemorrhages, emergency angiography was performed and revealed a pial single-channel arteriovenous fistula (AVF) in the early arterial phase with drainage into the dilated perimedullary vein. The feeding artery was a peripheral branch of the left anterior inferior cerebellar artery. There were no angiographical findings indicating a nidus or capillary network. The patient underwent left lateral suboccipital craniotomy. A small dilated perimedullary vein and an abnormally red spherical varix were found during the operation. A peripheral branch of the left anterior inferior cerebellar artery was thought to be a feeder because it seemed to be firmly attached to the dilated vein. Based on the operative technique for dural AVFs, electrocoagulation of the varix was performed aiming at obliteration of the fistula. The postoperative angiogram demonstrated the obliteration of the fistula and of the early filling vein. Feeders of cerebral AVF are cerebral arteries. A pial single-channel AVF is defined as a vascular malformation with a single venous channel in communication with one or more arteries with no intervening nidus or vessels. To date, reports in the literature of cerebral arteriovenous fistula have been very few. Its clinical entities such as origin, bleeding rate and the necessity of surgery remain subjects of debate. Here we report our experience and discuss its issues of the treatment we used.     

Treatment of acute focal cerebral ischemia and recirculation with d-propranolol

The purpose of the investigation was to evaluate the effects of d-propranolol upon temporary cerebral ischemia followed by a period of reperfusion, that is, a situation analogous to major cerebral artery embolization. Twenty adult cats, lightly anesthesized with nitrous oxide, underwent 4 hours of right middle cerebral artery (MCA) occlusion and 2 hours of recirculation. Ten cats were untreated and 10 cats received d-propranolol, the weak beta-blocking isomer of racemic (d,l) propranolol. The d-propranolol was infused directly into the right carotid artery at doses of 2 mg/kg, given as a bolus immediately before MCA occlusion, and 0.33 mg/kg/hour, given continuously for 6 hours beginning immediately after MCA occlusion. Systemic arterial blood pressure was similar in both groups, but heart rate was transiently reduced in the treated group immediately after the bolus injection of d-propranolol and MCA occlusion. Regional cerebral blood flow (rCBF), measured by the xenon-133 clearance technique, was not significantly different in the ischemic, right hemisphere. Electroencephalographic (EEG) activity changes in the ischemic, right hemisphere were similar in both groups, but there was significant deterioration of EEG activity in the left, nonischemic hemisphere of untreated cats after MCA reopening. Swelling of the ischemic, right hemispheres was similar in both groups and more severe than in previous studies wherein there was no recirculation phase. Carbon perfusion and blood-brain barrier changes were also similar. The results of the study failed to show a protective effect despite theoretical beneficial actions of d-propranolol. Also, the study demonstrated that d-propranolol does not have a detrimental effect upon rCBF in acute focal cerebral ischemia.     

The effect of Acetylcholinesterase inhibitor (SDZ ENA 713) for r-CBF and focal cerebral ischaemia

Summary The purpose of the present study was to examine the effect of Acetylcholinesterase inhibitor (AChEI) on r-CBF (group A) and its protecting effect on focal ischaemic cell damage (group B). The pial arterial diameter and the r-CBF were measured with a width analyzer and with a laser Doppler flowmeter through a cat cranial window on the ectosylvian gyrus. The ischaemic area was measured histologically. We used intravenous injection of AChEI([-](S)-N-ethyl-3-[(1-dimethyl-amino) ethyl]-N-methyl-phenylcarbamate, SDZENA713, Sands Pharmacy) to block AChE.Twenty minutes after injection AChEI (0.6 mg/kg) the pial arteriole dilated 108.5±1.8% and the r-CBF increased 115.4±2.6%. The pial arteriole dilated maximally to 137.6±6.5% at 120 minutes after injection and the r-CBF increased maximally to 137.1±19.5% at 60 minutes after injection.The protecting effect was evaluated using cats and 1 hour of occlusion of the middle cerebral artery (MCA). Twenty minutes after injection of AChEI, the pial arteriole dilated to 116.7±2.4% and the r-CBF increased to 111.9±2.6% significantly. During MC Aocclusion the r-CBF decreased to 24.7-41.4% in group B and 25.1–32.6% in sham group (group C). The pial arteriole dilated 145.0–184.0% in group C and 150.7–171.6% in group B during MCA occlusion and 30 minutes after reperfusion the pial arteriole returned to 120.0±3.3% in group C and 123.4±11.3% in group B. There were no significant changes in the r-CBF and in the vessel diameter between group B and C during the 2 hours after reperfusion. But 2.5 hours after reperfusion the pial arteriole began to redilate prominently in group C and 5 hours after reperfusion the pial arteriole redilated 118.3±4.2% in group B and 140.0±3.6% in group C. The percentage of infarcted area in sham animals (group C) measured 38.6±6.4% and significantly decreased to 26.2±7.8% in treated animals (group B).In conclusion, AChEI dilates cerebral arteries and increases CBF. AChEI protects ischaemic areas from parenchymal and vessel damage because of increasing collateral circulation in focal ischaemia.     

Effect of superoxide dismutase on acute reperfusion injury of the rabbit brain

Summary To study the involvement of free oxygen radicals of the blood-brain barrier (BBB) disruption during early reperfusion, we isolated the distal internal carotid artery, and the middle and anterior cerebral arteries via the transorbital approach in anesthetized rabbits. Using radiolabeled microspheres, regional cerebral blood flow (rCBF) was measured before, during and after 1-hour unilateral occlusion of these vessels. Fifty-five minutes after ischemia, animals received intravenous saline placebo (control), superoxide dismutase (SOD) at 8mg/kg=30000 U/kg, or weakened superoxide dismutase (wSOD) at 8mg/kg=30000 U/kg.Integrity of the BBB was assessed by leakage of Evan's Bluealbumin dye (EB-albumin dye), which was given at 15 minutes of reperfusion and allowed to circulate for an additional hour. In the control and wSOD-treated groups, rCBF decreased (26% and 40% of control, respectively) within the blue-tinted tissue of the occluded hemisphere during ischemia; hyperemia was observed during early reperfusion. In the control and wSOD-treated groups, EB-albumin dye leakage across the BBB increased 49% within the occluded hemisphere. However, within the SOD-treated group, the BBB showed minimal dye leakage even though rCBF of the occluded hemisphere (so-called blue-tinted tissue) decreased by 38% during ischemia. We conclude that 1-hour focal cerebral ischemia and reperfusion produce a vascular endothelial injury at the BBB. Since SOD administration showed significant protection, free-oxygen-radical production during early reperfusion is associated with break-down of the BBB to large molecules.