Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke

Variability in the effects of the intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat has been a common and disadvantageous finding. Therefore, we systematically investigated the effects of suture type and rat strain on outcome. First, the clinical and neuropathological effects of permanent MCAO with either an uncoated or a silicone-coated nylon suture were studied over 7  days in Sprague–Dawley rats ( n =36 for each type of suture). Outcome was less severe with the uncoated compared with the silicone-coated suture (e.g. total cerebral infarct volume at 24  h before any fatalities was 119.9±79.8  mm³ , cf. 183.0±36.5 mm³ , n =12 for each, P <0.05; and overall mortality rate was 12.5% cf. 33%, respectively), but much more variable (coefficient of variation was 66.6% cf. 19.9%, respectively). Second, being more consistent in its effects, the silicone-coated suture was further studied in Wistar and Fischer-344 rats ( n =12 for each). Seventy-five per cent of the Wistar's died prematurely from gross hemispheric oedema. Motor deficit and extent of infarction in the Fischer-344 rats were both significantly greater compared with Sprague-Dawley rats (e.g. total cerebral infarct volume at 24  h in the former was 253.6±25.4  mm³ , n =11, P <0.05), and more consistent (coefficient of variation was only 10.0%). It was concluded that the silicone-coated suture and the Fischer-344 rats strain produced the most consistent results and their novel combination provides a reliable acute stroke model.     

Middle cerebral artery ischemic stroke and COVID-19: a case report

Journal of NeuroVirology - We present a clinical case of a patient with SARS-CoV-2 infection and respiratory symptoms, complicated with a pro-thrombotic state involving multiple vascular...     

Temporary middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke and reperfusion

The intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat (the suture model) is a model of stroke which readily lends itself to studying the pathophysiology of post-ischaemic reperfusion. Unfortunately, variability of outcome has compromised the potential of the model, but systematic studies might characterize a consistent protocol. Therefore, the clinical and neuropathological outcome of temporary MCAO and reperfusion in the suture model were systematically investigated. Two hours or 4 h of MCAO were employed, measuring the extent of infarction at 24 h with triphenyltetrazolium chloride or at 72 h with histopathological techniques. Outcome was compared in three rat strains. Following 2 h of MCAO, motor function improved during reperfusion in Sprague-Dawley, but not in Wistar or Fischer-344 rats. All Sprague-Dawley and Wistar rats survived the protocol to 72 h, but 33% of Fischer-344 rats died. The extents of infarction and oedema were greater and less variable in Wistar and Fischer-344 than Sprague-Dawley rats, and in all three strains, the extent of infarction increased with reperfusion time. Following 4 h of MCAO, there was no improvement in motor function during reperfusion in Sprague-Dawley rats, and mortality was high at 24 h in Wistar (33%) and Fischer-344 rats (83%). Outcome was only pursued in Sprague-Dawley rats to 72 h, where the extent of infarction was quite variable. It was concluded that the extent and variability of outcome following temporary MCAO in the suture model is strain-dependent, and a consistent protocol with zero mortality was found in Wistar rats using 2 h of MCAO and 70 h of reperfusion.     

Middle cerebral artery stroke that includes the premotor cortex reduces mobility outcome.

BACKGROUND AND PURPOSE: The premotor cortex (PMC) (Brodmann 6) contributes uniquely to proximal upper and lower limb power and plays a role in the organization of motor behaviors. We assessed the degree to which PMC damage affected functional outcome. METHODS: We prospectively compared the functional outcome of patients with a first stroke in the middle cerebral artery distribution that either left the PMC intact (PMC-; n=19) or damaged the PMC (PMC+; n=12). The Functional Independence Measure for disability and the motor score of the Stroke Impairment Assessment Set for impairment assessed outcome. RESULTS: Demographic and clinical features and lesion volume were comparable for the PMC+ and PMC- groups. However, the PMC- group demonstrated significant gain in mobility and in proximal leg movement. This focal improvement contributed to the trend in the PMC- group toward greater independent ambulation. CONCLUSIONS: Decreased motor recovery of proximal lower limbs in humans with PMC damage supports the idea that it is the origin of corticoreticulospinal pathways that subserve proximal lower extremity function. Furthermore, persistent proximal weakness after PMC damage may amplify other motor impairments, which include defects in planning, initiating, and sequencing. Neurorehabilitation outcomes may contribute to a more detailed functional anatomy after stroke and partial recovery.     

Middle cerebral artery occlusive disease: The New England medical center stroke registry.

To analyze the clinical features, vascular lesions, and infarct distribution in Asian and white patients with middle cerebral artery (MCA) territory ischemia, we studied age, sex, race, risk factors, angiographic, and neuroimaging findings among patients in the New England Medical Center Stroke Registry. We included patients with well-defined intrinsic occlusive lesions of the MCAs and patients with embolic MCA territory infarcts. Among 695 patients in the stroke registry, 89 (12.8%) qualified. They had 28 MCA intrinsic stenoses, 17 MCA embolic occlusions (cardiogenic or unknown origin), and 44 carotid artery (CA) stenoses or occlusions. MCA intrinsic disease patients were more often Asians and women, and more often had hypertension. Asians were older than whites. Coronary artery disease (27%), peripheral vascular disease (20.5%), and smoking (39%) were more common in CA disease patients. The most common site of MCA intrinsic stenosis (78%) and embolic occlusion (59%) was the mainstem MCA. Infarcts in patients with MCA intrinsic disease mostly involved the striatocapsular area (61%). Infarcts in patients with MCA embolic occlusion (75%) and CA disease (43%) most often involved the parietal lobe. In our hospital, most patients with MCA intrinsic disease are Asians and women and have hypertension and striatocapsular infarctions. Asian patients are usually older than white patients. The most common site of vascular lesions is the mainstem MCA.     

Middle cerebral artery dolichoectasia in a young woman with a previous stroke

We observed a 32-year-old female who had suffered from a left hemisphere ischemic stroke with right hemiparesis at the age of seven. At that time, a CT scan demonstrated a left ischemic lesion in nucleo-capsular region and a cerebral angiogram documented a complete occlusion of the supraclinoid segment of the internal carotid artery. When we observed the patient neurological examination demonstrated a moderate right brachio-crural hemiparesis. A brain MRI showed an old ischemic lesion involving the left nucleo-capsular and 'flow voids' suggestive for a vascular malformation in the left sylvian region. A cerebral rotational angiogram with 3-D reconstructions demonstrated a dolichoectatic left middle cerebral artery with an unusual 'corkscrew' aspect. Middle cerebral artery dolichoectasia is a rare pathological condition that may manifest with a stroke. The patients with intracranial arterial dolichoectasia (IADE) are most often hypertensive elderly men, and, to the best of our knowledge, an ischemic stroke associated with IADE has never been reported in children.     

Transcranial doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) can demonstrate arterial occlusion and subsequent recanalization in acute ischemic stroke patients treated with intravenous tissue plasminogen activator (tPA). Limited data exist to assess the accuracy of recanalization by TCD criteria. METHODS: In patients with acute middle cerebral artery (MCA) occlusion treated with intravenous tPA, we compared posttreatment TCD with angiography (digital subtraction or magnetic resonance). On TCD, complete occlusion was defined by absent or minimal signals, partial occlusion by blunted or dampened signals, and recanalization by normal or stenotic signals. Angiography was evaluated with the Thrombolysis In Myocardial Ischemia (TIMI) grading scale. RESULTS: Twenty-five patients were studied (age 61+/-18 years, 16 men and 9 women). TCD was performed at 12+/-16 hours and angiography at 41+/-57 hours after stroke onset, with 52% of studies performed within 3 hours of each other. Recanalization on TCD had the following accuracy parameters compared with angiography: sensitivity 91%, specificity 93%, positive predictive value (PPV) 91%, and negative predictive value (NPV) 93%. To predict partial occlusion (TIMI grade II), TCD had sensitivity of 100%, specificity of 76%, PPV of 44%, and NPV of 100%. TCD predicted the presence of complete occlusion on angiography (TIMI grade 0 or I) with sensitivity of 50%, specificity of 100%, PPV of 100%, and NPV of 75%. TCD flow signals correlated with angiographic patency (chi(2)=24.2, P<0.001). CONCLUSIONS: Complete MCA recanalization on TCD accurately predicts angiographic findings. Although a return to normal flow dynamics on TCD was associated with complete angiographic resumption of flow, partial signal improvement on TCD corresponded with persistent occlusion on angiography.     

Middle cerebral artery occlusion methods in rat versus mouse models of transient focal cerebral ischemic stroke

<正>Experimental stroke research commonly employs focal cerebra ischemic rat models(Bederson et al.,1986a;Longa et al.,1989).In human patients,ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery,usually the middle cerebral artery(MCA).Experimental focal cerebral ischemia models have been employed to mimic human stroke(Durukan and Tatlisumak,2007).Rodent models of focal cerebral ischemia that     

Middle cerebral artery occlusion after cerebral hydatic embolism in a pediatric patient: case report

Stroke is a very uncommon complication of hydatic disease. The case of a pediatric patient who suffered cerebral infarction due to the occlussion of the right middle cerebral artery, and who subsequently developed multiple hydatic cysts in the territory of the occluded vessel, is presented. Even though the diagnostic tests aimed to detect a primary focus of the disease were negative, the existing data support the possibility of a cardiac embolic origin.     

Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion and reperfusion.

The adhesion of both leukocytes and platelets to microvascular endothelial cells has been implicated in the pathogenesis of ischemia/reperfusion (I/R) injury in several vascular beds. The objectives of this study were to (1) assess the platelet-leukocyte-endothelial cell interactions induced in the cerebral microvasculature by middle cerebral artery occlusion (MCAO)/reperfusion, and (2) define the molecular determinants of the prothrombogenic and inflammatory responses in this model of focal I/R. MCAO was induced for 1 hour in wild-type (WT) mice, WT mice treated with a monoclonal antibody (mAb) to either P-selectin or GPIIb/IIIa, and in P-selectin-/-(P-sel-/-) chimeras. Isolated platelets labeled with carboxyfluorescein diacetate succinimidyl ester (CFDASE) were administered intravenously and observed with intravital fluorescence microscopy. Leukocytes were observed after intravenous injection of rhodamine 6G. One hour of MCAO followed by 1 hour of reperfusion resulted in the rolling and adhesion of leukocytes in venules, and after 4 hours of reperfusion, the adhesion of both leukocytes and platelets was detected. Although both the P-selectin and GPIIb/IIIa mAbs significantly reduced the adhesion of leukocytes and platelets at 4 hours of reperfusion, the antiadhesive effects of the P-selectin mAb were much greater. The leukocyte and platelet adhesion responses were significantly attenuated in both P-sel-/- --> WT and WT --> P-sel-/- bone marrow chimeras, compared with WT --> WT chimeras. Neutropenia, induced by antineutrophil serum treatment, also reduced the recruitment of leukocytes and platelets after cerebral I/R. These findings implicate a major role for both platelet-associated and endothelial cell-associated P-selectin, as well as neutrophils in the inflammatory and prothrombogenic responses in the microcirculation after focal cerebral I/R.     

Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke

BACKGROUND AND PURPOSE: Leukocytes contribute to cerebral ischemia-reperfusion injury. However, few experimental models examine both in vivo behavior of leukocytes and microvascular rheology after stroke. The purpose of the present study was to characterize patterns of leukocyte accumulation in the cerebral microcirculation and to examine the relationship between leukocyte accumulation and microcirculatory hemodynamics after middle cerebral artery occlusion and reperfusion (MCAO-R). METHODS: Male rats (250 to 350 g) were anesthetized and ventilated. Tail catheters were inserted for measurement of arterial blood gases and administration of drugs. Body temperature was maintained at 37 degrees C. Animals were subjected to 2 hours of MCAO by the filament method. A cranial-window preparation was performed, and the brain was superfused with warm, aerated artificial cerebrospinal fluid. Reperfusion was initiated by withdrawing the filament, and the pial microcirculation was observed by use of intravital fluorescence microscopy. Leukocyte accumulation in venules, arterioles, and capillaries; leukocyte rolling in venules; and leukocyte venular shear rate were assessed during 1 hour of reperfusion. RESULTS: We found significant leukocyte adhesion in cerebral venules during 1 hour of reperfusion after 2 hours of MCAO. Leukocyte trapping in capillaries and adhesion to arterioles after MCAO-R tended to increase compared with controls, but the increase was not significant. We also found that shear rate was significantly reduced in venules during early reperfusion after MCAO. CONCLUSIONS: A model using the filament method of stroke and fluorescence microscopy was used to examine white-cell behavior and hemodynamics in the cerebral microcirculation after MCAO-R. We observed a significant increase in leukocyte rolling and adhesion in venules and a significant decrease in blood shear rate in the microcirculation of the brain during early reperfusion. Leukocytes may activate and damage the blood vessels and surrounding brain cells, which contributes to an exaggerated inflammatory component to reperfusion. The model described can be used to examine precisely blood cell-endothelium interactions and hemodynamic changes in the microcirculation during postischemic reperfusion. Information from these and similar experiments may contribute to our understanding of the early inflammatory response in the brain during reperfusion after stroke.     

Histopathological effects of delayed reperfusion after middle cerebral artery occlusion in the anesthetized baboon

In patients with middle cerebral artery (MCA) territory stroke, attempts to recanalize the brain are currently being extended beyond the classic 3-h time window. Mechanical thrombectomy is particularly attractive as it may carry lesser risks of severe hemorrhagic transformation than thrombolysis. However, whether late reperfusion per se promotes hemorrhagic transformation and increases infarct volume as compared to permanent occlusion is unclear. There is no study of the histopathologic sequelae of late reperfusion following MCA occlusion (MCAo) in the non-human primate. Five young adult baboons completed a specially designed protocol of 20-h MCAo (under etomidate anaesthesia), followed by 4-week survival and finally perfusion-fixation. Infarct volume was measured histologically using validated stereological methods. The results were compared to our previously published series of 6 h and permanent MCAo performed with identical experimental and post mortem procedures. An infarct was present in each baboon, consistently involving the caudate head, internal capsule and putamen; the adjacent inferior frontal cortex was involved in one subject. Infarct volume was significantly larger than with 6 h MCAo, as expected, but did not differ from permanent MCAo. There was no evidence of hemorrhage around the infarcted area in any animal. We found that following a 20 h ischemic episode, the infarct volume was similar to that found with permanent occlusion, with no evidence of hemorrhagic transformation. Cautiously extrapolating to the human situation, our findings suggest that even late mechanical recanalization may not promote brain damage and could be considered in selected cases.     

Olfactory and taste dysfunction after bilateral middle cerebral artery stroke.

Acquired dysfunction of the sense of smell and taste is usually associated with orbitofrontal tumors or trauma and is rarely reported to have occurred after ischemic stroke. We report on a patient who noted impairment of the sense of smell and taste after a localized insular frontoparietal stroke and who also had a similar, mirror-image infarction in the other hemisphere. Injury to an area of the cortex responsible for the integration of taste and smell may have accounted for this patient's symptoms.     

Effect of difluoromethylornithine on reperfusion injury after temporary middle cerebral artery occlusion.

Polyamines have been shown to play an important role in the disturbance of the blood-brain barrier (BBB) in a number of pathological states including ischemia. BBB disturbances may be almost completely prevented by treating animals with the ornithine decarboxylase (ODC) inhibitor, alpha-difluoromethylornithine (DFMO). DFMO has been also shown to prevent N-Methyl-D-aspartate (NMDA) toxicity in tissue cultures. It has been suggested that the pathological disturbances in polyamine metabolism observed following cerebral ischemia, particularly the post-ischemic increase in putrescine, may contribute to the ischemic injury that is most evident in the CA1 subfield of the hippocampus. In this study, effects of DFMO in cerebral ischemia and reperfusion were examined. The results showed that inhibition of the polyamine system by DFMO decreased ischemic injury volume and brain tissue water content in a dose-dependent manner, without change in vital signs, including systemic arterial blood pressure, arterial partial oxygen pressure, regional cerebral blood flow and body temperature.     

Middle cerebral artery velocity during upright posture after marijuana smoking.

Marijuana is known to cause symptoms suggestive of orthostatic hypotension such as dizziness and fainting during upright posture. We examined changes in cerebral blood velocity (CBV) and peripheral circulation during upright posture after smoking marijuana in 10 right-handed male subjects with a previous history of exposure to marijuana. The participants were physically and mentally healthy and drug-free for a minimum of 3 months before the experiment. Middle cerebral artery CBV, blood pressure and pulse rate were recorded during reclining position and standing, before and after smoking a high-potency marijuana cigarette or a placebo cigarette administered during 2 separate visits to the laboratory. The participants were questioned about dizziness during the upright position. Six of 10 subjects reported moderate to severe dizziness during standing after marijuana but not placebo. Subjects who experienced severe dizziness during standing showed marked decreases in blood pressure and CBV. Those who reported moderate dizziness showed reduction in CBV but not blood pressure. Subjects who reported mild dizziness after marijuana and after placebo smoking showed minimal changes in blood pressure and CBV. Cerebral ischemia during upright position after marijuana smoking may be caused by hypotension and impaired cerebral autoregulation.     

Association between pre-treatment perfusion profile and cerebral edema after reperfusion therapies in ischemic stroke

The relationship between reperfusion and edema is unclear, with experimental and clinical data yielding conflicting results. We investigated whether the extent of salvageable and irreversibly-injured tissue at baseline influenced the effect of therapeutic reperfusion on cerebral edema. In a pooled analysis of 415 patients with anterior circulation large vessel occlusion from the Tenecteplase-versus-Alteplase-before-Endovascular-Therapy-for-Ischemic-Stroke (EXTEND-IA TNK) part 1 and 2 trials, associations between core and mismatch volume on pre-treatment CT-Perfusion with cerebral edema at 24-hours, and their interactions with reperfusion were tested. Core volume was associated with increased edema (p < 0.001) with no significant interaction with reperfusion (p = 0.82). In comparison, a significant interaction between reperfusion and mismatch volume (p = 0.03) was observed: Mismatch volume was associated with increased edema in the absence of reperfusion (p = 0.009) but not with reperfusion (p = 0.27). When mismatch volume was dichotomized at the median (102 ml), reperfusion was associated with reduced edema in patients with large mismatch volume (p < 0.001) but not with smaller mismatch volume (p = 0.35). The effect of reperfusion on edema may be variable and dependent on the physiological state of the cerebral tissue. In patients with small to moderate ischemic core volume, the benefit of reperfusion in reducing edema is related to penumbral salvage.