Impaired microvascular filling after focal cerebral ischemia in monkeys

1972 ◽  
Vol 36 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Robert M. Crowell ◽  
Yngve Olsson
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Cerebrovascular Diseases ◽  
Subcortical Structures ◽  
Content Type ◽  
Microsurgical Technique ◽  
Small Vessels ◽  
Mca Occlusion ◽  
Vascular Channels ◽  
Fine Print

✓ 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.

Thresholds of focal cerebral ischemia in awake monkeys

1981 ◽  
Vol 54 (6) ◽  
pp. 773-782 ◽  
Author(s):  
Thomas H. Jones ◽  
Richard B. Morawetz ◽  
Robert M. Crowell ◽  
Frank W. Marcoux ◽  
Stuart J. FitzGibbon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neurological Function ◽  
Local Flow ◽  
Content Type ◽  
Mca Occlusion ◽  
Fine Print

✓ 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.

Induction of cyclooxygenase-2 messenger RNA after transient and permanent middle cerebral artery occlusion in rats: comparison with c-fos messenger RNA by using in situ hybridization

1999 ◽  
Vol 91 (6) ◽  
pp. 1005-1012 ◽  
Author(s):  
Hiroyuki Kinouchi ◽  
Haiyen Huang ◽  
Shouichi Arai ◽  
Kazuo Mizoi ◽  
Takashi Yoshimoto
Keyword(s):  
In Situ Hybridization ◽  
Cerebral Ischemia ◽  
Messenger Rna ◽  
Focal Cerebral Ischemia ◽  
Brain Regions ◽  
Content Type ◽  
Mca Occlusion ◽  
Cox 2 ◽  
Fine Print

Object. Recently, two different cyclooxygenase (COX) genes, COX-1 and -2, were identified. In this study, topographic and chronological profiles of COX-2 messenger (m)RNA and c-fos mRNA expression were investigated using in situ hybridization after focal cerebral ischemia.Methods. Rats undergoing permanent ischemia were decapitated at 30 and 90 minutes and at 2, 4, 8, and 24 hours after middle cerebral artery (MCA) occlusion, and rats undergoing transient ischemia were decapitated at 4, 8, and 24 hours after MCA occlusion that lasted for either 30 or 90 minutes. After brief transient MCA occlusion, c-fos mRNA was induced in the whole MCA territory, adjacent cortex (cingulate cortex), and distant brain regions such as the hippocampus and substantia nigra. In contrast, COX-2 mRNA was not induced in the ischemic core (lateral striatum) but only in the penumbral area (MCA cortex). Long transient and permanent MCA occlusion did not induce c-fos and COX-2 mRNAs in the ischemic core but strongly induced both mRNAs in the penumbral area (medial striatum and periphery of MCA cortex) and adjacent cortex (cingulate cortex). In brain regions distant from the ischemic territory, although c-fos mRNA was induced in the thalamus, substantia nigra, and hippocampus after extended transient and permanent occlusion, COX-2 mRNA was only induced in the bilateral hippocampi. The induction of COX-2 mRNA persisted in all locations even at 24 hours after MCA occlusion.Conclusions. The distribution of COX-2 mRNA induction was apparently different from that of c-fos mRNA after MCA occlusion. These results pertaining to COX-2 mRNA agree well with the previous observations of changes in prostaglandin metabolism induced by focal cerebral ischemia. However, whether this induction of the COX-2 gene contributes to the histopathological outcome of cerebral ischemia remains to be elucidated.

Delayed induction and long-term effects of mild hypothermia in a focal model of transient cerebral ischemia: neurological outcome and infarct size

2001 ◽  
Vol 94 (1) ◽  
pp. 90-96 ◽  
Author(s):  
Carolina M. Maier ◽  
Guo Hua Sun ◽  
David Kunis ◽  
Midori A. Yenari ◽  
Gary K. Steinberg
Keyword(s):  
Cerebral Ischemia ◽  
Mild Hypothermia ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Brain Slices ◽  
Long Term Effects ◽  
Content Type ◽  
Mca Occlusion ◽  
Group 10 ◽  
Fine Print

Object. The goals of this study were to determine the effects of delaying induction of mild hypothermia (33°C) after transient focal cerebral ischemia and to ascertain whether the neuroprotective effects of mild hypothermia induced during the ischemic period are sustained over time. Methods. In the first study, rats underwent 2 hours of middle cerebral artery (MCA) occlusion. Animals in one group were maintained under normothermic conditions (N group, 23 rats) throughout the period of ischemia and reperfusion. Rats in four additional groups were exposed to 2 hours of hypothermia, which commenced at ischemia onset (H0 group, 11 rats) or with delays of 90 (H90 group, 10 rats), 120 (H120 group, 10 rats), or 180 (H180 group, five rats) minutes, and allowed to survive for 3 days. In the second study, animals underwent 1.5 hours of MCA occlusion and were maintained under normothermic (48 rats) or hypothermic (44 rats) conditions during the ischemia period, after which they survived for 3 days, 1 week, or 2 months. All animals were evaluated for neurological findings at 24 hours and 48 hours postischemia and before they were killed. Regions of infarct were determined by examining hematoxylin and eosinstained brain slices obtained at six coronal levels. Conclusions. Mild hypothermia conferred significant degrees of neuroprotection in terms of survival, behavioral deficits, and histopathological changes, even when its induction was delayed by 120 minutes after onset of MCA occlusion (p < 0.05) compared with normothermic conditions. Furthermore, the neuroprotective effect of mild hypothermia (2-hour duration) that was induced during the ischemia period was sustained over 2 months. These studies lend further support to the use of mild hypothermia in the treatment of stroke.

Neuroprotective effect of postischemic administration of progesterone in spontaneously hypertensive rats with focal cerebral ischemia

2000 ◽  
Vol 92 (5) ◽  
pp. 848-952 ◽  
Author(s):  
Yoshiaki Kumon ◽  
Soon C. Kim ◽  
Paul Tompkins ◽  
Alan Stevens ◽  
Saburo Sakaki ◽  
...  
Keyword(s):  
Body Weight ◽  
Cerebral Ischemia ◽  
Neurological Deficit ◽  
Spontaneously Hypertensive Rats ◽  
Focal Cerebral Ischemia ◽  
Hypertensive Rats ◽  
Content Type ◽  
Spontaneously Hypertensive ◽  
Mca Occlusion ◽  
Fine Print

Object. Exogenous progesterone has been shown to reduce brain edema and ischemia-induced cell damage and to improve physiological and neurological function during the early stage of focal cerebral ischemia. In the present study, the authors assessed the neuroprotective potential of progesterone during the late stage of ischemia in a transient middle cerebral artery (MCA) occlusion model in the rat.Methods. Forty-eight male spontaneously hypertensive rats were randomly assigned to six groups. Progesterone was dissolved in dimethyl sulfoxide (DMSO). In four groups of rats, the dissolved progesterone (4 mg/kg or 8 mg/kg) was administered for 2 or 7 days after ischemia. In two control groups DMSO was administered for 2 or 7 days after ischemia. Occlusion of the MCA was induced by insertion of an intraluminal suture, and reperfusion was accomplished by withdrawal of the suture. Treatment was initiated on reperfusion, which followed 2 hours of MCA occlusion, and continued once a day. Lesion volume, neurological deficit, and body weight loss were measured 2 or 7 days after ischemia, depending on the animal group.Treatment with a high dose of progesterone (8 mg/kg) resulted in reductions in lesion size, neurological deficits, and body weight, compared with control rats.Conclusions. Administration of progesterone to male rats 2 hours after MCA occlusion reduces ischemic brain damage and improves neurological deficit even 7 days after ischemia.

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

1989 ◽  
Vol 70 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Toshihiko Kuroiwa ◽  
Makoto Shibutani ◽  
Riki Okeda
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Reactive Hyperemia ◽  
Diffusion Method ◽  
Left Middle Cerebral Artery ◽  
Content Type ◽  
Bbb Opening ◽  
Fine Print

✓ 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.

Decompressive craniectomy in a rat model of “malignant” cerebral hemispheric stroke: experimental support for an aggressive therapeutic approach

1996 ◽  
Vol 85 (5) ◽  
pp. 853-859 ◽  
Author(s):  
Arnd Doerfler ◽  
Michael Forsting ◽  
Wolfgang Reith ◽  
Christian Staff ◽  
Sabine Heiland ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Decompressive Craniectomy ◽  
Control Group ◽  
Acute Ischemia ◽  
Vessel Occlusion ◽  
Content Type ◽  
Time Points ◽  
Infarction Size ◽  
Mca Occlusion ◽  
Fine Print

✓ Acute ischemia in the complete territory of the carotid artery may lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Although clinical data suggest that patients benefit from undergoing decompressive surgery for acute ischemia, little data about the effect of this procedure on experimental ischemia are available. In this article the authors present results of an experimental study on the effects of decompressive craniectomy performed at various time points after endovascular middle cerebral artery (MCA) occlusion in rats. Focal cerebral ischemia was induced in 68 rats using an endovascular occlusion technique focused on the MCA. Decompressive cranioectomy was performed in 48 animals (in groups of 12 rats each) 4, 12, 24, or 36 hours after vessel occlusion. Twenty animals (control group) were not treated by decompressive craniectomy. The authors used the infarct volume and neurological performance at Day 7 as study endpoints. Although the mortality rate in the untreated group was 35%, none of the animals treated by decompressive craniectomy died (mortality 0%). Neurological behavior was significantly better in all animals treated by decompressive craniectomy, regardless of whether they were treated early or late. Neurological behavior and infarction size were significantly better in animals treated very early by decompressive craniectomy (4 hours) after endovascular MCA occlusion (p < 0.01); surgery performed at later time points did not significantly reduce infarction size. The results suggest that use of decompressive craniectomy in treating cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. By performing decompressive craniectomy neurosurgeons will play a major role in the management of stroke patients.

The therapeutic value of nimodipine in experimental focal cerebral ischemia

1987 ◽  
Vol 67 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Isabelle M. Germano ◽  
Henry M. Bartkowski ◽  
Mary E. Cassel ◽  
Lawrence H. Pitts
Keyword(s):  
Cerebral Ischemia ◽  
Mechanism Of Action ◽  
Neurological Outcome ◽  
Focal Cerebral Ischemia ◽  
Ischemic Insult ◽  
Double Blind ◽  
Content Type ◽  
Therapeutic Value ◽  
Fine Print ◽  
Neuropathological Evaluation

✓ Recent studies suggest that nimodipine, a potent calcium-channel antagonist that causes significant cerebrovascular dilatation, may improve neurological outcome after acute experimental permanent focal cerebral ischemia when given before or immediately after occlusion of the middle cerebral artery (MCA) in various animals. The authors describe the effect of nimodipine on cerebral ischemia in a rat model. At 1,4, or 6 hours after occlusion of the MCA, rats were treated in a double-blind technique with either nimodipine, placebo, or saline. Neurological and neuropathological evaluation was performed at 24 hours. Neurological outcome was better in rats treated with nimodipine 1, 4, or 6 hours after occlusion (p < 0.001, p < 0.01, p < 0.05, respectively), and the size of areas of infarction was statistically smaller in nimodipine-treated groups (p < 0.01, p < 0.01, p < 0.05, respectively) when compared with control rats treated with saline or placebo. The best neurological outcome and the smallest area of infarction were found in nimodipine-treated rats 1 hour after occlusion. Compared with controls, the size of the periphery of the infarcted area was smaller in nimodipine-treated rats. The results show that nimodipine improves neurological outcome and decreases the size of infarction when administered up to 6 hours after ischemic insult. These results suggest a possible mechanism of action of nimodipine on the “penumbra” of the ischemic area.

S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage

1989 ◽  
Vol 71 (5) ◽  
pp. 727-731 ◽  
Author(s):  
Hans-Göran Hårdemark ◽  
Nils Ericsson ◽  
Zbigniew Kotwica ◽  
Gerd Rundström ◽  
Ib Mendel-Hartvig ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Neuron Specific Enolase ◽  
Experimental Models ◽  
Neurological Injury ◽  
Content Type ◽  
Mca Occlusion ◽  
S 100 ◽  
Fine Print

✓ Cerebrospinal fluid (CSF) markers of brain damage are potentially capable of providing quantitative information about the extent of certain neurological injury. The presence of such markers in CSF after brain damage is transient and it is essential to understand their kinetics if they are to be used in clinical practice. In the present study, the CSF concentrations of two neurospecific proteins, S-100 protein and neuron-specific enolase (NSE), were determined in rats before and repeatedly after one of two types of experimental brain damage: traumatic cortical injury and focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. The two types of experimental brain damage resulted in significant differences in the kinetics of S-100 and NSE concentrations in CSF. Cortical contusion was followed by a rapid increase in both S-100 and NSE and a peak occurred in both after about 7½ hours, at which time the values declined toward normal. A second, smaller peak was seen after about 1½ days. The increase and decrease in S-100 and NSE levels in CSF was slower after MCA occlusion; a peak was seen after 2 to 4 days. Furthermore, S-100 was generally higher than NSE after trauma, whereas after MCA occlusion the NSE concentration was slightly higher than the S-100 value. These results support the use of CSF markers for estimation of the extent of brain damage in experimental models and forms a basis for the understanding of their kinetics, which is important for their use in clinical practice.

Delayed treatment with magnesium: reduction of brain infarction and improvement of electrophysiological recovery following transient focal cerebral ischemia in rats

2005 ◽  
Vol 102 (6) ◽  
pp. 1085-1093 ◽  
Author(s):  
E-Jian Lee ◽  
Ming-Yang Lee ◽  
Guan-Liang Chang ◽  
Li-Hsuan Chen ◽  
Yu-Ling Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Content Type ◽  
Delayed Treatment ◽  
Cerebral Ischemia Reperfusion ◽  
Fine Print

Object. The authors examined whether delayed treatment with Mg++ would reduce brain infarction and improve electrophysiological and neurobehavioral recovery following cerebral ischemia—reperfusion. Methods. Male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion for 90 minutes followed by 72 hours of reperfusion. Magnesium sulfate (750 µmol/kg) or vehicle was given via intracarotid infusion at the beginning of reperfusion. Neurobehavioral outcome and somatosensory evoked potentials (SSEPs) were examined before and 72 hours after ischemia—reperfusion. Brain infarction was assessed after the rats had died. Before ischemia—reperfusion, stable SSEP waveforms were recorded after individual fore- and hindpaw stimulations. At 72 hours of perfusion the SSEPs recorded from ischemic fore- and hindpaw cortical fields were depressed in vehicle-injected animals and the amplitudes decreased to 19 and 27% of baseline, respectively (p < 0.001). Relative to controls, the amplitudes of SSEPs recorded from both ischemic fore- and hindpaw cortical field in the Mg++-treated animals were significantly improved by 23% (p < 0.005) and 39% (p < 0.001) of baselines, respectively. In addition, Mg++ improved sensory and motor neurobehavioral outcomes by 34% (p < 0.01) and 24% (p < 0.05), respectively, and reduced cortical (p < 0.05) and striatal (p < 0.05) infarct sizes by 42 and 36%, respectively. Conclusions. Administration of Mg++ at the commencement of reperfusion enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral ischemia—reperfusion. Because Mg++ has already been used clinically, it may be worthwhile to investigate it further to see if it holds potential benefits for patients with ischemic stroke and for those who will undergo carotid endarterectomy.

Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia

1992 ◽  
Vol 77 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Bruce I. Tranmer ◽  
Ted S. Keller ◽  
Glenn W. Kindt ◽  
David Archer
Keyword(s):  
Cardiac Output ◽  
Cerebral Ischemia ◽  
Blood Volume ◽  
Volume Expansion ◽  
Focal Cerebral Ischemia ◽  
Brain Regions ◽  
Ischemic Brain ◽  
Content Type ◽  
Blood Volume Expansion ◽  
Fine Print

✓ Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% ± 92%, mean ± standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% ± 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p < 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia.

Sign in / Sign up

Export Citation Format

Share Document