Unilateral Common Carotid Artery Ligation Research Articles

Progressing cerebral infarction in relation to plasma glucose in gerbils.

We studied neurologic morbidity and its evolution during hyperglycemia induced immediately after permanent unilateral common carotid artery ligation in Mongolian gerbils. A total of 60 animals were divided into five groups: one experiencing severe hyperglycemia for 1 hour after the onset of ischemia (brief hyperglycemia group, n = 13), a normoglycemic control group for the brief hyperglycemia group (n = 12), a group with severe hyperglycemia for 4 hours after the onset of ischemia (prolonged hyperglycemia group, n = 11), a normoglycemic control group for the prolonged hyperglycemia group (n = 13), and a hyperosmolar normoglycemic control group for the prolonged hyperglycemia group (n = 11). Neurologic morbidity and mortality were higher in the two hyperglycemic groups than in the three normoglycemic control groups. The neurologic deficit progressed according to the duration of severe hyperglycemia. In the three normoglycemic control groups neurologic status stabilized 120 minutes after the onset of ischemia, in the brief hyperglycemia group stabilization occurred at 210 minutes, and in the prolonged hyperglycemia group neurologic deficit progressed for approximately 360 minutes, coinciding with the death of all but one gerbil, in which the neurologic deficit remained stable until death 23 hours after ischemia. We suggest that hyperglycemia is another cause of progressing cerebral infarction.

Mannitol therapy in perinatal hypoxic-ischemic brain damage in rats.

To study the efficacy of mannitol in reducing cerebral edema and improving the ultimate neuropathologic outcome in perinatal cerebral hypoxia-ischemia, 67 7-day postnatal rats were subjected to unilateral common carotid artery ligation followed by exposure to 8% oxygen at 37 degrees C for 3 hours. Twenty-seven rat pups received a subcutaneous injection of 0.1 ml mannitol in a dosage of 4 mg/kg body wt immediately following cerebral hypoxia-ischemia and every 12 hours thereafter for a total of four doses. Control animals received either no therapy (n = 16) or an equivalent volume of normal saline (n = 24). Mannitol injections in six rat pups not subjected to hypoxia-ischemia produced no mortality but significantly increased serum osmolality from 287 to 361 mos/l (p less than 0.01). Preliminary studies indicated that substantial mortality occurred when greater doses of mannitol were administered to rats. After 48 hours of recovery from hypoxia-ischemia, the animals were killed and their brains were examined for either tissue water content (33 rat pups) or the presence of neuropathologic alterations (34 rat pups). Mannitol significantly reduced (p less than 0.001) brain water content, as a reflection of cerebral edema, in both the ipsilateral (88.5% compared with 90.6% in controls) and the contralateral (85.0% compared with 87.2% in controls) cerebral hemispheres. Mannitol therapy did not ameliorate the incidence, distribution, or severity of tissue injury in the cerebral cortex, subcortical white matter, hippocampus, striatum, or thalamus of the ipsilateral cerebral hemisphere compared with the controls. Thus, while mannitol substantially reduces the extent of cerebral edema following hypoxia-ischemia, no beneficial affect on ultimate brain damage occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Blood Flow and Edema in Perinatal Hypoxic-Ischemic Brain Damage

The relationship between cerebral blood flow (CBF) and the evolution of brain edema was investigated in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-d postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37 degrees C. This insult produces neuronal necrosis and/or infarction only in the cerebral hemisphere ipsilateral to the arterial occlusion in the majority of animals; hypoxia alone produces no damage. CBF, measured by the indicator diffusion technique using iodo[14C]-antipyrine, and tissue water content were determined concurrently in both cerebral hemispheres at specific intervals during recovery from cerebral hypoxia-ischemia. Water contents in the ipsilateral cerebral hemisphere were 89.1, 89.6, 89.7, 91.0, and 88.3% at 30 min, 4 h, 24 h, 3 d, and 6 d, respectively (p less than 0.001); whereas the percent tissue water in the contralateral hemisphere was unchanged from values in nonligated, hypoxic control rats (87.7%). CBF was similar in both cerebral hemispheres at 30 min, 4 h, and 24 h of recovery (50-65 mL/100 g/min) and not different from age-matched controls. At 3 and 6 d, CBF in the ipsilateral cerebral hemisphere was 30 and 26% of the contralateral hemisphere and 23 and 29% of the control animals, respectively (p less than 0.001). No inverse correlation existed between the changes in brain water content and CBF at any interval until 6 d of recovery. Thus, an early hypoperfusion does not follow perinatal cerebral hypoxia-ischemia, as occurs in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate and Energy Metabolism during the Evolution of Hypoxic-Ischemic Brain Damage in the Immature Rat

The brain damage that evolves from perinatal cerebral hypoxia-ischemia may involve lingering disturbances in metabolic activity that proceed into the recovery period. To clarify this issue, we determined the carbohydrate and energy status of cerebral tissue using enzymatic, fluorometric techniques in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-day postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37 degrees C. This insult is known to produce tissue injury (selective neuronal necrosis or infarction) predominantly in the cerebral hemisphere ipsilateral to the carotid artery occlusion in 92% of the animals. Rat pups were quick-frozen in liquid nitrogen at 0, 1, 4, 12, 24, or 72 h of recovery; littermate controls underwent neither ligation nor hypoxia. Glucose in both cerebral hemispheres was nearly completely exhausted during hypoxia-ischemia, with concurrent increases in lactate to 10 mmol/kg. During recovery, glucose promptly increased above control values, suggesting an inhibition of glycolytic flux, as documented in the ipsilateral cerebral hemisphere by measurement of glucose utilization (CMRglc) at 24 h. Tissue lactate declined rapidly during recovery but remained slightly elevated in the ipsilateral hemisphere for 12 h. Phosphocreatine (P approximately Cr) and ATP in the ipsilateral cerebral hemisphere were 14 and 26% of control (p less than 0.001) at the end of hypoxia-ischemia; total adenine nucleotides (ATP + ADP + AMP) also were partially depleted (-46%).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of growth retardation on perinatal hypoxic-ischemic brain damage

The effect of growth retardation on the extent of brain damage produced by hypoxia-ischemia was assessed in immature rats. Newborn rats were raised in litters of 6 or 14 pups from day 2 to 7. On postnatal day 7, those immature rats raised in litters of 14 weighed 18% less than animals raised in litters of 6 ( P < 0.001). They then were subjected to cerebral hypoxia-ischemia by unilateral common carotid artery ligation followed by 3 h of exposure to 8% oxygen-92% nitrogen at 37°C. Upon return to their dams, all litters were culled to 6 pups. At 30 days of age, the animals underwent perfusion-fixation of their brains under pentobarbital anesthesia. Brain damage was assessed by measuring the length and width of each cerebral hemisphere. The extent of brain damage varied from no difference in the size of the two cerebral hemispheres to marked shrinkage of the hemisphere ipsilateral to the common carotid artery occlusion. The range of brain damage between the well-nourished and poorly nourished animals was comparable. Rank order of the extent of damage demonstrated significantly greater tissue injury in those animals well nourished prior to hypoxia-ischemia (Mann-Whitney U-test; P = 0.003). The results indicate that nutritional deprivation in the immature rat is associated with a decreased rather than increased susceptibility to brain damage arising from hypoxiaischemia. The findings of the investigation have relevance to the human infant suffering from intrauterine growth retardation (IUGR).

Regional cerebral glucose utilization in the immature rat: effect of hypoxia-ischemia.

The 2-deoxy-[14C]-glucose (2-DG) method of Sokoloff was used to assess regional cerebral glucose utilization (CGU) in the immature rat. The 7-d postnatal rats received 2.5 muCi 2-DG subcutaneously, after which blood was collected for measurement of plasma glucose and 2-DG activity at intervals up to 90 min. The brains of the 90-min rat pups either were frozen for analysis of glucose concentration and chromatographic separation of 2-DG and 2-DG-6-phosphate or for [14C]-autoradiography. A lumped constant of 0.55 was calculated from plasma and brain glucose levels of 6.4 and 1.62 mmol/L.kg, respectively. Of the [14C] activity in brain, 75.6% was in the 2-DG-6-phosphate fraction; this percent was substituted for K1*, K2*, and K3* in the Sokoloff equation. Cerebral hemispheric CGU (n = 6) averaged 11.4 +/- 1.5 mumol/100 g/min, 1/10 the value of adult rat brain. Rates in 16 brain structures (n = 10) ranged from 7.8 (frontal white matter) to 16.9 (cerebellum) mumol/100 g/min. During hypoxia-ischemia (unilateral common carotid artery ligation combined with exposure to 8% oxygen), the lumped constant increased to 1.04, and 99% of 2-DG was converted to 2-DG-6-phosphate. Increases in CGU occurred in all eight structures of the cerebral hemisphere ipsilateral to the carotid artery occlusion (n = 9), ranging from 287% (frontal white matter) to 445% (striatum) of control values (p less than 0.05). Relatively comparable elevations in CGU (234-435% of control) occurred in the contralateral cerebral hemisphere, which were not significantly different from those of the ipsilateral hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity of the developing rat brain to hypobaric/ischemic damage parallels sensitivity to N-methyl-aspartate neurotoxicity

The endogenous excitotoxin, glutamate (Glu), acting at the N-methyl-aspartate (NMA) subtype of Glu receptor, is thought to play a major role in hypoxic/ischemic neuronal degeneration. In the present study, the sensitivities of the developing rat CNS to hypoxic/ischemic neuronal degeneration and to the neurotoxic action of NMA were compared at various postnatal ages. In the hypoxic/ischemic experiments, ischemia was produced by unilateral common carotid artery ligation and hypoxia by subjecting the pups to a partial vacuum. Keeping the duration of the hypobaric episode constant at 75 min for all age groups, we observed that the vulnerability of the immature brain to hypobaric/ischemic damage increased during the early neonatal period (days 2-4), reached a peak at day 6 and then diminished progressively with increasing age. In the second part of the study, NMA was microinjected unilaterally into the head of the caudate nucleus at various postnatal ages (2-80 d). In the early neonatal period (days 2-6), injections of relatively small doses of NMA (6-15 nmol) produced a dose-dependent widespread excitotoxic reaction throughout the forebrain with peak sensitivity being observed on day 6. The cytotoxic reaction to NMA was identical in appearance and time course to that induced by hypobaric/ischemic methods. With increasing age, the excitotoxic response to a given dose of NMA decreased progressively and the lesions became more strictly confined to the injection site. Cell populations most sensitive to NMA toxicity in the 2-10 d period closely correlated with those most vulnerable to hypoxia/ischemia, and sensitivity to both types of injury reached a peak at 6 d. These findings reinforce other evidence linking an excitotoxic mechanism and the NMA subtype of Glu receptor to hypoxic/ischemic brain damage and suggest that there may be a period during development when NMA receptors are hypersensitive to excitotoxic stimulation, thus rendering the neurons possessing such receptors hypervulnerable to hypoxic/ischemic damage.

MK-801 prevents hypobaric-ischemic neuronal degeneration in infant rat brain

Recent evidence implicates the endogenous excitatory amino acids, glutamate (Glu) and aspartate, in hypoxic/ischemic neuronal degeneration. In a preceding article (Ikonomidou et al., 1989) we described a new model for studying hypoxic/ischemic neuronal degeneration in the infant rat brain that entails unilateral common carotid artery ligation followed by exposure to a partial vacuum for 75 min. Promising features of this model include a low mortality rate and high incidence of acute brain damage disseminated over numerous brain regions. In addition, there is a striking similarity between the type of cytopathology characterizing this model of hypoxic/ischemic neuronal degeneration and that which has been described in infant animals treated with Glu. MK-801 is a powerful antagonist of the N-methyl-D-aspartate (NMDA) receptor ionophore complex (a subtype of Glu receptor). In the present study, after unilateral carotid artery ligation was performed on 10-d-old rat pups, they were treated either with MK-801 (1 mg/kg i.p.) or saline 15 min before exposure to the hypobaric condition. MK-801 exerted a strong neuroprotective effect without serious side effects; the majority of saline control animals sustained severe brain damage, whereas the majority of MK-801-treated pups had no brain damage. These and other recent findings suggest that the NMDA receptor may play an important role in hypoxic/ischemic neuronal degeneration in the immature brain and provide hope that NMDA antagonists such as MK-801 may be effective in preventing such degeneration.

Synthesis of the major inducible heat shock protein in rat hippocampus after neonatal hypoxia-ischemia

Rats aged 7 days were exposed to 3.5 h of cerebral hypoxia-ischemia produced by unilateral common carotid artery ligation combined with hypoxia (8% oxygen). The major inducible heat-shock protein, HSP-68, was synthesized in ipsilateral but not contralateral (control) hippocampus during early recovery (1 and 3 h). HSP-68 synthesis was not detected during longer recovery periods. The presence of HSP-68 was confirmed by Western blotting and immunostaining with a polyclonal antibody to HSP-68.

Calcium accumulation during the evolution of hypoxic-ischemic brain damage in the immature rat.

An excessive accumulation of calcium in neuronal and other tissues has been postulated to represent a "final common pathway" for cell death arising from hypoxia-ischemia. To clarify the role of altered calcium flux into and distribution within the perinatal brain undergoing hypoxic-ischemic injury, 7-day postnatal rats underwent unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in greater than 90% of the animals. Either before or after hypoxia-ischemia, the animals received a subcutaneous injection of [45Ca]Cl2, and their brains were subjected to 45Ca autoradiography at 0-1, 5, 24, and 72 h, 7 or 15 days thereafter. During hypoxia-ischemia, calcium flux into the ipsilateral cerebral hemisphere was prominent in 13 of 14 rat pups, especially in neocortex, hippocampus, striatum, and thalamus. Calcium accumulation also occurred to a variable degree (6 of 14 animals) in the contralateral cerebral hemisphere. During recovery, radioactivity in the contralateral cerebral hemisphere was no longer apparent, whereas in the ipsilateral hemisphere, the extent of calcium accumulation was mild in four of six at 1 h, moderate in three of six at 5 h, moderate to intense in six of seven and six of seven at 24 and 72 h, respectively, and intense in three of three and two of two animals at 7 and 15 days, respectively. As during hypoxia-ischemia, the distribution of the radioactivity was most prominent in those structures that are known to be vulnerable to hypoxic-ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral hypoxia-ischemia in immature rats: Methodological considerations

We used a model of perinatal hypoxic/ischemic brain damage which combines unilateral common carotid artery ligation and hypoxia (8% O 2). Protein synthesis inhibition and cell loss were found in the ipsilateral forebrain of 11-day-old rats when hypoxia was initiated 4 h but not 24 h after carotid ligation. [ 14C]Iodoantipyrine uptake studies suggest that compensating vascular changes which protect the ipsilateral forebrain occur within 24 h of carotid ligation.

Regional cerebral blood flow during hypoxia-ischemia in immature rats.

Immature rats subjected to a combination of unilateral common carotid artery ligation and hypoxia sustain brain damage confined largely to the ipsilateral cerebral hemisphere. To ascertain the extent and distribution of ischemic alterations in the brains of these small animals, we modified the Sakurada technique to measure regional cerebral blood flow using carbon-14 autoradiography. Seven-day-old rats underwent right common carotid artery ligation following which they were rendered hypoxic with 8% O2 at 37 degrees C. Before and during hypoxia, the rat pups received an injection of iodo[14C]antipyrine for determination of regional cerebral blood flow. Blood flows to individual structures of the ipsilateral cerebral hemisphere were not influenced by arterial occlusion alone; flows to the contralateral hemisphere and to the brainstem and cerebellum actually increased by 25-50%. Hypoxia-ischemia was associated with decreases in regional cerebral blood flow of the ipsilateral hemisphere such that by 2 hours, flows to subcortical white matter, neocortex, striatum, and thalamus were 15, 17, 34, and 41% of control, respectively. The hierarchy of the blood flow reductions correlated closely with the distribution and extent of ischemic neuronal necrosis. However, unlike the pathologic pattern of this model, the degree of ischemia appeared homogeneous within each brain region. Blood flows to contralateral cerebral hemispheric structures were relatively unchanged from prehypoxic values, whereas flows to the brainstem and cerebellum nearly doubled and tripled, respectively. Thus, ischemia is the predominant factor that determines the topography of tissue injury to major regions of immature rat brain, whereas metabolic factors (intrinsic vulnerability) may influence the heterogeneous pattern of damage seen within individual structures.

1712 GLUCOSE SUPPLEMENTATION DOES NOT ACCENTUATE HYPOXICISCHEMIC BRAIN DAMAGE IN IMMATURE RATS: BIOCHEMICAL MECHANISMS

Previous investigations from our laboratory have shown that hyperglycemia during the course of hypoxia-ischemia (H-I) does not increase brain damage in immature animals as occurs in adults (Voorhies et al 1982). To clarify biochemical mechanisms responsible for this age specific paradox, we subjected 7-day postnatal rats to unilateral common carotid artery ligation followed by the hypoxia produced by the inhalation of 8% oxygen for 2hr (Rice et al, 1981). Experimental animals received 0.1 ml. 50% glucose sc 15 min prior to onset of hypoxia, which increased blood glucose to 350 mg/dl for 2 hr. Glucose in the cerebral hemisphere ipsilateral to the carotid occlusion was exhausted by 20 min of H-I in control (saline injected) rats but not until 2 hr in glucosetreated animals. Brain lactate and puruvate increased to a greater extent in the glucose-treated animals but only at 20 and 60 min, such that L/P ratios were comparable at 2 hr. Declines in ATP and P-creatine occurred earlier in control animals, but by 2 hr low levels were seen in both groups. Total adenine nucleotides also were depleted to the same degree. The findings indicate that despite an early protective influence of glucose on brain glycolytic intermediates & high energy reserves during cerebral H-I, the effect is short lived even with continuing hyperglycemia. Limited glucose entry into the immature brain at any blood glucose level retards anaerobic metabolism during H-I; which, in turn, leads to a disruption of the energy state of the tissue and ultimate brain damage. (NIH #HD-15738).

Immunohistopathologic analysis of olfactory degeneration caused by ischemia.

The development of olfactory dysfunction caused by ischemia was studied in Mongolian gerbils. Mongolian gerbils frequently have an anomaly of the cerebral circulation and are susceptible to brain ischemia or infarction following ligation of a single common carotid artery. Ischemia was induced by unilateral common carotid artery ligation or temporary occlusion of both common carotid arteries, and the olfactory pathway was examined. In the olfactory pathway of the forebrain, ischemic changes were observed in the lateral olfactory tract, olfactory tubercle, olfactory ventricle, and anterior olfactory nucleus. The olfactory bulb was resistant to ischemia. Partial or complete degeneration of the ipsilateral olfactory neuroepithelium was observed in some gerbils that survived more than 14 days after the onset of ischemia. Immunohistopathologic analysis of the neuroepithelium for the olfactory marker protein revealed that functional damage of the olfactory neurons occurred in some gerbils within the first few days after the ischemic event.

Naloxone exacerbates hypoxic-ischemic brain injury in the neonatal rat

Recent reports suggest that naloxone, an opiate antagonist, may adversely affect the asphyxiated fetus. We found that naloxone exacerbated hypoxic-ischemic brain injury in the 7-day-old rat subjected to unilateral common carotid artery ligation and hypoxia. Moreover, there was no amelioration of systemic acidosis or brain edema in naloxone-treated animals compared to animals treated with saline solution. High doses of naloxone may reduce the resistance of the fetus to hypoxic stress.

Effects of dexamethasone in hypoxic-ischemic brain injury in the neonatal rat.

To clarify the effects of corticosteroids in neonatal hypoxic-ischemic brain injury, 7-day-old rats were subjected to unilateral common carotid artery ligation and hypoxia (Levine procedure) after being injected subcutaneously with saline, low-dose dexamethasone (4 mg/kg) or high-dose dexamethasone (40 mg/kg). Neither low-dose nor high-dose dexamethasone ameliorated the brain edema, lactacidemia, or hypoglycemia associated with hypoxia-ischemia. In addition, dexamethasone did not alter the pattern of neuropathologic damage or reduce the fall in brain high-energy phosphates. Finally, high-dose dexamethasone-treated animals experienced significantly more mortality than did either saline- or low-dose dexamethasone-treated animals. In this model of neonatal hypoxia-ischemia, dexamethasone did not confer any significant cerebral protection.

The influence of immaturity on hypoxic-ischemic brain damage in the rat.

Brain damage in the Levine preparation (unilateral common carotid artery ligation with hypoxia) consists of ischemic neuronal alterations in the ipsilateral forebrain. As the model has been restricted to adult animals, unilateral common carotid artery ligation was carried out in 7-day-postnatal rats. Four to 8 hours later the 25 pups were exposed to 8% oxygen at 37 degrees C for 3.5 hours. Controls consisted of littermates subjected to carotid ligation without subsequent hypoxia, hypoxia without prior ligation, and neither ligation nor hypoxia. After hypoxia the animals were returned to their dams and appeared normal for up to 50 hours. All pups were then killed by perfusion-fixation. Moderate to severe ischemic neuronal changes were seen in the ipsilateral cerebral cortex, striatum, and hippocampus in at least 90% of the animals and included infarction in 56% of the brains. Cortical damage was occasionally laminar but more often occurred in columns at right angles to the pial surface. Unlike adult animals, there was necrosis of white matter, greater ipsilaterally, originating in and spreading from myelinogenic foci. The evolution of ischemic cell change and the associated gliomesodermal reaction was more rapid than in the adult. In 22 additional pups subjected to carotid artery ligation and hypoxia, brains were analyzed for water content. Significant increases (0.6 to 3.3%) in water content of the ipsilateral hemispheres occurred in 11 of 22 brains (50%). Unilateral ischemia combined with hypoxia in developing rats therefore results in neuronal destruction in the same brain regions as in adult animals, but also causes necrosis of white matter. The incidence of increased water content was similar to that of overt infarction. Thus, as previously shown in the adult, brain edema is a consequence rather than a cause of major ischemic damage in the immature animal.

Asymmetry of turning behaviour of rats induced by amphetamine and apomorphine.

Turning behaviour of rats following injection of amphetamine is in the same direction as following apomorphine. Unilateral common carotid artery ligation does not affect this asymmetry. Thus the reason for the asymmetry in turning behaviour following injection of amphetamine is probably due to postsynaptic dopaminergic asymmetry within the corpus striatum.

Rotational behavior in gerbils following unilateral common carotid artery ligation.

Unilateral cerebral infarctions are produced in 30-50% of all gerbils subjected to ipsilateral ligation of a common carotid artery. It has previously been shown that this infarction is associated with a major depletion if ipsilateral brain dopamine. The present studies characterize the spontaneous and drug-induced rotational behavior manifested by these animals and attempt to relate it to the functional activity of dopaminergic synapses. The tendency of animals to turn towards the side of the lesion 2-3 hours after surgery was found to correlate highly with the unilateral dopamine depletion observed after 24 hours. Two patterns of rotational responses were observed among animals showing symptoms that were treated with d-amphetamine or apomorphine; these could be correlated with mortality 24 hours after surgery.

On the relationship of brain vasculature to production of neurological deficit and morphological changes following acute unilateral common carotid artery ligation in gerbils

The known susceptibility of the Mongolian gerbil to cerebral infarction following unilateral carotid artery ligation has been attributed in the past to the demonstrated absence of an anastomotic supply between the anterior and posterior cerebral circulations. In a study of 34 adult gerbils exposed to such a procedure, 11, or 33%, developed severe neurological sequelae and succumbed to the procedure in less than 30 hr, whereas 23 animals survived with only minor or transient neurological signs. All animals displayed the expected lack of an anastomosis between the anterior and posterior circulations, but, in addition, the animals which survived the procedure were found to have a prominent early cross-connection between the anterior cerebral arteries, whereas the animals which succumbed had no such connection. Neuropathological changes in susceptible animals were apparent as early as 3 1 2 hr after ligation and consisted of edema, initially perivascular and then intraneuronal, followed by acute necrosis. A variety of other vascular anomalies was encountered. We conclude that the peculiar susceptibility of Mongolian gerbils to cerebral infarction following acute unilateral common carotid artery ligation is not related primarily to lack of adequate collaterals between the anterior and posterior circulations, but to the degree of adequacy of communication between the anterior cerebral arteries. The critical difference may be more one of degree, i.e. the point at which the medial branches of the anterior cerebral artery fuse to become an azygos vessel, rather than an actual difference in the pattern of distribution of the anterior cerebral arteries. The presence of other variations in vascular supply in a relatively small series suggests that results of similar studies of infarction and response to treatment be interpreted with caution.