Neurosurgical Forum: Letters to the Editor To The Editor Robert P. Iacono , M.D. Reuven R. Sandyk , M.Sc., M.D. University of Arizona Health Sciences Center Tucson, Arizona 425 427 The recent paper by Baskin, et al. , reports prolonged survival following experimentally induced cerebral ischemic deficits in cats treated with opioid antagonists (Baskin DS, Hosobuchi Y, Grevel JC: Treatment of experimental stroke with opiate antagonists. Effects on neurological function, infarct size, and
Effects on neurological function, infarct size, and survival
David S. Baskin, Yoshio Hosobuchi and Joachim C. Grevel
hypertensive stroke-prone rat (SHR-SP). Soc Neurosci Abstr 8: 248, 1982 (Abstract) 10. Faden AI : Opiate antagonists in the treatment of stroke. Stroke 15 : 565 – 578 , 1984 Faden AI: Opiate antagonists in the treatment of stroke. Stroke 15: 565–578, 1984 11. Faden AI , Hallenbeck JM , Brown CQ : Treatment of experimental stroke: comparison of naloxone and thyrotropin releasing hormone. Neurology 32 : 1083 – 1087 , 1982 Faden AI, Hallenbeck JM, Brown CQ: Treatment of experimental stroke
Ronald R. Reed, Conrad Ciesel and Guy Owens
modified mass spectrometer. This permits, for the first time, the focal study of tissue gases. Seizures are known to increase both cerebral metabolism and cerebral blood flow, yet it is not known whether the increase in brain perfusion is sufficient to meet or possibly exceed the brain's increased metabolic demands during seizure activity. Our present study was undertaken to assess quantitatively the ability of seizure activity to elevate pO 2 in the ischemic brain tissue produced by experimental “strokes.” Methods Mongrel dogs, anesthetized with pentathol and
Seiji Hayashi, Daniel G. Nehls, Charles F. Kieck, Juan Vielma, Umberto DeGirolami and Robert M. Crowell
✓ The authors performed a controlled study of induced hypertension therapy for treatment of experimental stroke in unanesthetized monkeys. Ten control and 10 treated animals were subjected to a 4-hour occlusion of the middle cerebral artery (MCA) by an implanted tourniquet. Neurological status and local cerebral blood flow (CBF) were monitored serially. Local CBF was determined by hydrogen clearance in and around the elevated 20% to 40% by intravenous infusion of phenylephrine hydrochloride. Neuropathological evaluation was performed after about 2 weeks.
A 4-hour occlusion of the MCA in control animals caused moderate stable neurological deficits, moderate stable decreases in local CBF, and medium-sized infarcts. With induced hypertension, five of 10 treated animals showed neurological improvement, and eight exhibited increased CBF in the ischemic zone. Average infarct size tended to be smaller in the treated group, although the difference did not reach statistical significance. Hemorrhagic infarcts were not observed. In four animals, phenylephrine caused cardiac dysrhythmias and hypotension which were reversed by appropriate measures. In this unanesthetized primate model of moderate experimental stroke, induced hypertension had beneficial effects on neurological status, local CBF, and infarct size without causing hemorrhagic infarction. Induced hypertension may be beneficial for some clinical cases of focal cerebral ischemia.
Robert J. Hariri, Elizabeth L. Supra, John Paul Roberts and Michael H. Lavyne
blockade in the treatment of experimental stroke. Some investigators advocate this form of intervention, reporting improved neurological outcome following experimental stroke; 8, 29, 37 others have demonstrated no improvement in laboratory preparations 4, 24, 26, 30, 40 or in non-blinded clinical trials. 6, 32 Previously we have examined the changes in basal ganglion blood flow during the 72-hour time period following transient global cerebral ischemia (TGI) using the rat model of Pulsinelli and Brierley. 43 We found that caudate blood flow increased to values
Jong Eun Lee, Yone Jung Yoon, Michael E. Moseley and Midori A. Yenari
enhancement on T 1 -weighted images compared with normothermia (38°C) (six hypothermic and seven normothermic animals; *p < 0.05, **p < 0.01). Mild hypothermia decreases MMP expression but increases TIMP-2 expression after experimental stroke. Immunohistochemical staining was performed to determine the anatomical distribution of both MMP-2 and MMP-9 and whether this was influenced by hypothermia. Both MMP-2 and MMP-9 appeared predominantly within the ipsilateral ischemic cortex, but some staining was also observed in the ischemic striatum, and no staining was
Robert M. Crowell and Yngve Olsson
✓ Impairment of microvascular filling was demonstrated in relation to focal cerebral ischemia in the monkey. Temporary or sustained middle cerebral artery (MCA) clipping was achieved with a microsurgical technique. Animals were sacrificed by perfusion with a carbon black suspension. Brains were fixed in formalin, and the extent of microvascular carbon filling was estimated grossly and microscopically. In most animals, MCA occlusion of 2 hours to 7 days produced diminished filling in small vessels in the MCA territory of supply. The impairment of filling was most pronounced in the deep subcortical structures but also affected the cortex in some animals. Temporary and sustained occlusion of equal duration produced roughly equivalent areas of abnormal filling. The impairment of vascular filling tended to be more extensive with increasing duration of occlusion. Hypotension during MCA occlusion caused almost total non-filling of the microvasculature in the entire MCA territory. Impaired filling of vascular channels may play a role in the pathogenesis of some clinical cerebrovascular diseases.
Mary K. Hammock, Giovanni Di Chiro and Apichati Pongpatirojana
✓ A technique for placement of an indwelling carotid artery catheter in the rhesus monkey is presented. These indwelling catheters have proved useful in the investigation of regional cerebral blood flow using xenon-133, positive contrast angiography, and fluorescein angiography. Although limited thus far to studies in experimental anemic stroke, this technique could be adapted to a variety of experimental situations in which serial evaluations of the cerebral vasculature are indicated.
Thomas H. Jones, Richard B. Morawetz, Robert M. Crowell, Frank W. Marcoux, Stuart J. FitzGibbon, Umberto DeGirolami and Robert G. Ojemann
✓ An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites.
Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed.
These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.
Richard J. Wurtman and Nicholas T. Zervas
dopaminergic stimulation. It can be conjectured that this “free” dopamine could act on postsynaptic dopaminergic receptors, on neurons that do not normally receive dopaminergic inputs, and on local blood vessels. The effects of dopamine on blood flow in the brain remain to be characterized; however, this monoamine is known to act with considerable potency on blood vessels in other parts of the body, for instance, the kidney. Obviously, further studies are necessary to determine the causes and consequences of the depletion of brain dopamine that follows such experimental