✓ A new model for establishing a successful and consistent arterial recirculation has been devised following middle cerebral artery (MCA) occlusion in the rat. A snare ligature was introduced at the stem of the MCA just distal to the lenticulostriate branches, and occlusion and recirculation were performed by pulling and releasing the thread. This method had an advantage over the use of a small clip which caused damage to the artery without good recirculation. Study of local cerebral blood flow using carbon-14 (14C)-iodoantipyrine, of cerebrovascular permeability using 14C-aminoisobutyric acid, and of brain-water content using the microgravimetric technique was performed upon recirculation following various periods of occlusion and compared with the results in permanent ischemia. A reactive hyperemia was noted within the previously ischemic area immediately upon recirculation following either a 30-minute or a 2-hour ischemic period. One or 2 hours later, delayed hypoperfusion developed in this region, but the circulation over the periphery of the ischemic area recovered well. Cerebrovascular permeability was not, however, altered during the time courses studied. Topographic changes in tissue specific gravity were compared between permanent and transient ischemia in the corresponding time-courses. Although there was a greater decrease in tissue specific gravity following recirculation when the ischemic period was maintained longer, edema formation was resolved by recirculation. Further study is required to determine thresholds of ischemic brain damage and edema formation at recirculation following focal cerebral ischemia.
Cerebral blood flow, cerebrovascular permeability, and brain edema
Taku Shigeno, Graham M. Teasdale, James McCulloch and David I. Graham
David I. Graham and Michael R. Bond
✓ A case of solitary intradural spinal ossifying schwannoma is presented in a patient whose symptoms and signs indicated a lesion at the level of the cauda equina.
Lawrence F. Marshall, Hume Adams, David Doyle and David I. Graham
✓ The preparation of smears from neurosurgical biopsy material is one technique by which a rapid diagnosis may be made available to the neurosurgeon. This technique is particularly appropriate for the small soft pieces of tissue obtained by needle biopsy. The 190 consecutive smear biopsies examined in this Institute during 1971 were reviewed and compared with subsequent paraffin sections of the same biopsies. In 94% of cases the correct diagnosis was obtained from the smears. Most of the errors stemmed from failure to distinguish between different types of malignant tumor. It is suggested that the smear technique is the most appropriate available for rapid neurosurgical diagnosis.
E. J. Sinar, A. David Mendelow, David I. Graham and Graham M. Teasdale
✓ Late pathophysiological events after the production and subsequent removal of an intracerebral mass were investigated using a mechanical microballoon model to simulate intracerebral hemorrhage. Immediately following balloon inflation in the caudate nucleus of rats, there was a significant increase in intracranial pressure to 14 ± 1 mm Hg (mean ± standard error of the mean), accompanied by a reduction in cerebral blood flow (CBF) in the ipsilateral frontal cortex, as measured by the hydrogen-clearance technique. Carbon-14-iodoantipyrine autoradiography revealed a significant reduction in the CBF of the ipsilateral caudate nucleus 4 hours after balloon inflation: 31% of the caudate nucleus had a CBF of less than 20 ml ⋅ 100 gm−1 ⋅ min−1 compared to only 1% in the sham-treated control group (balloon insertion without inflation). The rats with an intracerebral mass exhibited a significant increase in the volume of ischemic damage in the ipsilateral caudate nucleus (17.1% of total volume) compared to only 1.7% in the sham-treated group; however, there was no evidence of cerebral edema. Ischemic damage and reduced CBF persisted for 4 hours after transient inflation of a microballoon in the caudate nucleus. This suggests that ischemic damage occurs at the time of formation of the lesion and is not prevented by its early removal.
Fredrik P. Nath, Alistair Jenkins, A. David Mendelow, David I. Graham and Graham M. Teasdale
✓ A model of experimental intracerebral hemorrhage is described in which carefully controlled volumes of autologous blood were injected at arterial pressure into the caudate nucleus of the rat. A comparison of intracranial pressure changes and local cerebral blood flow (CBF) was made between three groups of rats, each receiving different injection volumes, and sham-operated control rats by monitoring intraventricular pressure and by obtaining quantitative autoradiographic measurements of CBF within 1 minute of the experimental hemorrhage. Cerebral blood flow was reduced both around the hematoma and in the surrounding brain. This change was strongly volume-dependent and was not accompanied by significant alterations in cerebral perfusion pressure. This finding suggests that the degree of ischemia at the time of an intracerebral bleed depends on the size of the lesion, and implicates local squeezing of the microcirculation by the hematoma, rather than a generalized alteration in perfusion pressure, as the cause of ischemia.
Thomas A. Kingman, A. David Mendelow, David I. Graham and Graham M. Teasdale
✓ Cerebral blood flow (CBF) was measured at different times during the first 150 minutes following an experimental space-occupying lesion produced with a 50-µl microballoon in rats. Local CBF was measured with the carbon-14-labeled iodoantipyrine quantitative autoradiographic technique. A region of local ischemia developed around the mass, while the remote effects of the mass were minimal. The focal ischemic lesion enlarged with time, and simulated removal of the lesion within this design did not alleviate the ischemia.
David I. Graham, Peter Macpherson and Lawrence H. Pitts
✓ The correlation between angiographic vasospasm, hematoma, and ischemic brain damage was studied in 29 patients who died as a result of subarachnoid hemorrhage following rupture of a saccular aneurysm. None of these patients was treated surgically. A comprehensive neuropathological examination was undertaken in each case. A significant relationship between the presence and degree of vasospasm and ischemic brain damage was found. Furthermore, even though intracerebral hematoma probably increased the risk of infarction associated with vasospasm, hematoma per se did not increase the incidence of ischemic brain damage.
A. David Mendelow, David I. Graham, Ursula I. Tuor and William Fitch
✓ The purpose of this study was to determine in subhuman primates whether hemodynamic mechanisms (as compared with embolic mechanisms) contribute to cerebral ischemia following carotid artery occlusion or stenosis. Following carotid artery occlusion there was loss of cerebral autoregulation: cerebral blood flow (CBF) measured with the xenon-133 technique became passively dependent upon the mean arterial blood pressure (MABP) over an MABP range of 30 to 110 mm Hg. By contrast, autoregulation was preserved in normal animals and in animals with a 90% carotid artery stenosis. Regional CBF was measured with carbon-14-labeled iodoantipyrine autoradiography in normotensive baboons, in hypotensive animals, and in hypotensive animals with carotid artery occlusion or stenosis. With carotid artery occlusion and hypotension, reduced levels of local CBF were seen ipsilaterally in the boundary zones between the anterior and middle cerebral arteries with 35% of the area of an anterior section through the hemisphere displaying a CBF value of less than 20 ml/100 gm/min. Comparable values with hypotension were 21% with carotid artery stenosis, 20% with no proximal vascular lesion, and 1% in normotensive animals. These areas of reduced CBF corresponded with areas of boundary-zone ischemia seen with light microscopy. The study suggests that while hemodynamic ischemia develops with carotid artery occlusion, it does not occur with even a 90% carotid artery stenosis or in normal animals.
Histopathological analysis and temporal patterns of cerebral blood flow disturbances
Peter Mathew, Ross Bullock, David I. Graham, William L. Maxwell, Graham M. Teasdale and James McCulloch
✓ The authors have devised a simple reproducible rodent model of focal cortical injury that uses a mechanical suction force applied through intact dura. The time course and pattern of changes in neurons, glia, and microvasculature were investigated using this model. Early traumatic disruption of the blood-brain barrier and hemorrhage do not occur in this model; however, many of the features of human contusion seen with light and electron microscopy are closely reproduced. At the site of injury, early swelling and lucency of neural dendritic processes have been shown to precede an astrocyte response. In the absence of perivascular hemorrhage, delayed perivascular protein leakage and polymorphonuclear infiltration of the damaged cortex occurs, which is suggestive of an acute inflammatory response. Cerebral blood flow (CBF) has been measured using 14C-iodoantipyrine autoradiography at 30 minutes, 4 hours, and 24 hours after induction of negative-pressure injury in rats anesthetized with halothane and in time-matched sham-operated controls. A significant reduction in blood flow in the sensorimotor cortex at the site of the injury was present at 30 minutes, 4 hours, and 24 hours after induction of the lesion, compared to the contralateral cortex (superficial lamina, ipsilateral 50 ± 7 ml/100 g/minute, contralateral 112 ± 26 ml/100 g/minute). The CBF was significantly reduced at the ipsilateral entorhinal cortex at 30 minutes postinjury but no significant reduction was demonstrated at later time points. Although marked alterations in CBF occurred in this cortical injury model, the magnitude and duration of the reduction in CBF are not consistent with those necessary for production of ischemic cell damage. These data indicate that this model of cortical injury can be used to examine biomechanical aspects of contusion without domination by ischemic pathophysiology.
The effect of halothane-induced hypotension
George W. Tyson, Graham M. Teasdale, David I. Graham and James McCulloch
✓ A quantitative autoradiographic technique that utilizes carbon-14-aminoisobutyric acid (14C-AIB) as a tracer was used to study alterations in cerebral microvascular permeability in 15 rats. Five were “sham-operated” controls and 10 underwent microsurgical, unilateral occlusion of the proximal middle cerebral artery (MCA). Histological changes indicative of focal cerebral ischemia were observed in only the latter 10 animals. These changes were confined to tissue normally perfused by the occluded MCA. After MCA occlusion, five animals were also subjected to transient halothane-induced hypotension (mean arterial blood pressure 50 mm Hg) for 20 to 30 minutes. Only in these five animals were blood-to-brain transfer constants (ki) significantly increased (by approximately 100%) at 4 hours after MCA occlusion. The topographical distribution of this alteration in cerebral microvascular permeability corresponded closely with the histological changes. Neither proximal MCA occlusion nor halothane-induced hypotension alone was associated with any focal or diffuse increase in ki after 4 hours.