Behavioral changes after focal cerebral ischemia by left middle cerebral artery occlusion in rats

Behavioral changes after occlusion of the left middle cerebral artery (MCA) in rats were investigated for 16 weeks. Impairment of motor coordination and incidence of neurological deficits including hemiplegia and abnormal posture were present for the first 2 and 4 weeks after MCA occlusion, respectively. Learning behavior in one-trial passive avoidance task was disturbed for the entire 16-week period when rats were trained at days 3 after MCA occlusion. Reacquisition was also impaired when rats were retrained on 8 weeks after MCA occlusion. Except for synchronized EEG at days 2 after MCA occlusion, significant changes in spontaneous movement and EEG were not observed in the MCA-occluded group. These results suggest that this rat model of MCA-occlusion is useful for quantitatively measuring functional changes in chronic phase of focal cerebral ischemia.     

Brain edema after middle cerebral artery occlusion

The right middle cerebral artery (MCA) was occluded either during 30 min or permanently, in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The rats were killed 2, 6 or 24 h later. Brain specific gravity, an indicator of brain edema, was determined on samples from the prefrontal, frontal, parietal and occipital cortex and the caudate nucleus. In SHR the brain specific gravity was significantly reduced in the right hemisphere at 2, but not at 6 or 24 h after a temporary occlusion. After permanent ligation, the specific gravity markedly decreased with time in the right hemisphere in SHR with significant difference from WKY, as well as from the left hemisphere, at all intervals. Our data support the concept that chronic hypertension aggravates ischemic brain edema after an arterial ligation.     

Regional cerebral blood flow after occlusion of the middle cerebral artery

Occlusions of the middle cerebral artery (MCA) are mostly of embolic origin (appr. 80%) and give rise to about one third of all ischemic strokes, most of these being major strokes. MCA occlusions lasting for less than 1/2 h are tolerated without occurrence of permanent tissue damage. Occlusions lasting between 1/2 h to 4-8 h lead to permanent tissue damage and neurological deficits that are proportional to the duration of occlusion. Maximal tissue damage is obtained after 4-8 h occlusion. A cerebral blood flow of 8-23 ml/100 gr/min is sufficient for cellular viability but insufficient for normal tissue function ("ischemic penumbra"). Cellular function is completely abolished in the interval 8-16 ml/100 gr/min and flow at that level is tolerated only for 1-3 h before neuronal death ensues. In the interval 18-23 ml/100 gr/min there is some functional activity although it is reduced. Experimental and clinical evidence suggests that flow in this interval may be tolerated for several days, months or even longer ("chronic ischemic penumbra"). After MCA occlusion the blood flow falls below 8 ml/100 gr/min in most cases and permanent MCA occlusion always leads to relatively large areas of frank infarction. The ischemic infarcts may be surrounded by collaterally perfused areas where the blood flow is pressure-dependent (impaired autoregulation) and quite commonly insufficient for normal neuronal function (below 23 ml/100 gr/min). Such collaterally perfused areas may include a "chronic ischemic penumbra". Emboli causing MCA occlusions commonly disintegrate and/or migrate more peripherally within the first few weeks post stroke. This leads to reperfusion and changes of ischemic infarcts into hyperemic infarcts where flow is severely increased. The vascular reactivity is completely abolished in hyperemic infarcts and the hyperemic state lasts for about two weeks. Probably, anemic infarcts are equivalent to ischemic infarcts while the hemorrhagic variety is equivalent to hyperemic infarcts. The "partial infarct" with selective neuronal necrosis occurs in experimental animals after MCA occlusions of less than four h but not after permanent MCA occlusion. The significance of partial infarction in human stroke is not clarified. The extent of irreversible tissue damage can be reduced only if therapy sets in within 4-8 h after the occlusion. If a "chronic penumbra" exists the extension of reversible tissue damage can be reduced if therapy aimed at increasing the blood flow in the penumbra sets in within weeks or even months after the stroke.(ABSTRACT TRUNCATED AT 400 WORDS)     

Proximal posterior cerebral artery occlusion simulating middle cerebral artery occlusion

We describe 12 cases of acute stroke in which clinical features of proximal posterior cerebral artery occlusion simulated the clinical syndrome of middle cerebral artery occlusion. The majority of patients developed contralateral hemiparesis, homonymous hemianopia, hemispatial neglect, and sensory loss or sensory inattention. All 8 patients with dominant hemisphere lesions were aphasic. Accurate diagnosis in each case was achieved only after a head CT, showing occipital lobe, thalamic, and inferomesial temporal lobe infarction. "Cortical" signs are probably explained by thalamic involvement. Recognition of this syndrome has implications for management and prognosis.     

Sensorimotor impairments in rats with cerebral infarction, induced by unilateral occlusion of the left middle cerebral artery: strain differences and effects of the occlusion site

Enormous differences exist between rat strains with respect to the infarct volume induced by unilateral middle cerebral artery (MCA) occlusion. We performed three experiments to address the following questions. Firstly, whether the pattern of MCA-occlusion (MCA-O) induced sensorimotor impairments in rats are strain dependent; secondly, whether proximal (i.e., close to its origin) and distal occlusions (above the lenticulostriate branch) of the MCA affect infarct volume and the behavioral impairments to a different extent; and thirdly, whether there is a relationship between the infarct volume and behavioral deficits. We found that the pattern of sensorimotor malfunctions induced by proximal unilateral MCA-O were highly strain dependent. Of the eight strains tested, Winkelmann-Wistar rats, Spontaneously Hypertensive Stroke-Prone rats, and Wistar-Kyoto rats were most severely affected. By contrast, Brown-Norway rats showed only mild behavioral deficits after the MCA-O. The second experiment confirmed that proximal occlusions induced slightly more behavioral malfunctions than distal occlusions did. Histological evaluation of the brain damage caused by proximal and distal MCA-O, confirmed that distal MCA-O damaged nearly exclusively cortical areas, and spared the caudate/putamen. An exploratory analysis of the relationship between infarct volume and behavioral deficits did not indicate that the severity of sensorimotor malfunctions can be predicted from the size of the infarct.     

Effect of right middle cerebral artery occlusion on striatal dopaminergic function

Summary Following right middle cerebral artery occlusion in the rat, striatal dopaminergic system alterations were studied. Dopamine turnover was assessed by measuring 3,4-dihydroxyphenylacetic acid concentrations and dopamine receptor function, by measuring (³H)-Spiroperidol binding. There was a transient decrease in 3,4-dihydroxyphenylacetic acid and permanent damage to dopamine receptors, as indicated by a time-dependent progressive reduction in the number of (³H)-Spiroperidol binding sites. The receptor deficit also manifested as turning behaviour towards the lesioned side 4 weeks after the lesion following subcutaneous apomorphine. Long-term changes of dopaminergic receptor activity in this experimental model of cerebral infarction may be secondary to cortical degeneration following middle cerebral artery occlusion.     

Critical cerebral blood flow for production of hemiparesis after unilateral carotid occlusion in the gerbil.

Transient cerebral ischaemia, produced by temporary unilateral common carotid artery (CCA) occlusion, was studied in the gerbil by means of chronically implanted hydrogen electrodes. Unilateral CCA occlusion produced behavioural signs of neurological deficit only when regional cerebral blood flow values in the ipsilateral cerebral hemisphere fell below a critical range of 0.20-0.22 ml/gm brain/min. Postischaemic poor perfusion (no-reflow) was an infrequent observation after removal of CCA occlusion.     

Unilateral occlusion of the middle cerebral artery after varicella-zoster virus infection

We report a 4-year-old child who developed hemiplegia 6 months after varicella-zoster virus (VZV) infection. Cerebral angiography showed complete occlusion of the right middle cerebral artery with basal moyamoya vessels. Elevation of anti-VZV antibody in the cerebrospinal fluid indicated central nervous system involvement. The association between VZV cerebral angitis and unilateral occlusion of right middle cerebral artery is discussed.     

An autopsy case of Neuro-Beh?et's disease with the right middle cerebral artery occlusion on cerebral angiogram

A case of Neuro-Beh?et's disease with the right cerebral artery occlusion on cerebral angiogram was reported. A 63 years old man complained of headache and slight fever without exacerbations of ocular and mucocutaneous lesions, 16 years after he had suffered from recurrent oral aphthous ulcers, genital ulcers, uveitis and erythema nodosum. Laboratory examination demonstrated pleocytosis in the cerebrospinal fluid, a low density area with contrast enhancement in right temporal and parietal lobes in brain CT, a high signal intensity in the same area in T2-weighted image in brain MRI and the occlusion of the right middle cerebral artery on cerebral angiogram. After admission, left homonymous hemianopsia and hemiparesis appeared. With steroid therapy, these symptoms diminished and abnormal findings in brain CT and MRI disappeared, but psychiatric symptoms were exacerbated gradually. Finally he died of agranulocytosis and pneumonia. Neuropathologic findings showed panarteritis of branches of the right middle cerebral artery and infarction of its territories in addition to perivascular infiltrations and foci of demyelination which were prominent in the cerebral basal regions.     

构建大脑中动脉阻塞脑缺血模型大鼠的类型分析

背景：线栓法造成短暂性大脑中动脉阻塞是研究大鼠局灶性脑缺血普遍使用的模型制作方法。但制作大鼠脑缺血模型的类型存在一定差异,可能导致实验结果的偏差。 目的：分析大脑中动脉阻塞线栓法制作大鼠脑缺血模型的类型及其影响因素。 方法：雄性SD大鼠166只,参照Longa线栓法造模,术后24 h行MRI扫描,根据扫描结果将大鼠分成皮质梗死组、皮质下梗死组及无梗死组,分析造模时线栓插入的深度。 结果与结论：皮质梗死组、皮质下梗死组和无梗死组大鼠的线栓插入深度分别为(19.9±0.9),(19.0±1.1)和(17.7±1.3) mm,皮质梗死组大鼠的线栓插入最深,而无梗死组的线栓插入最浅(P < 0.01)。提示插入深度不同导致的大鼠脑梗死的类型也不同,线栓插入越深,皮质梗死的概率可能越大。     

Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion

This study describes local immune responses in cerebral ischemia induced by permanent occlusion of the middle cerebral artery (MCAO) in the rat. The temporal and spatial pattern of leukocyte infiltration was characterized immunocytochemically using monoclonal antibodies against CD5, a pan T cell marker, against CD4 and CD8 for subtyping of T lymphocytes, and ED1, a marker for macrophages. CD5⁺ T cells were present in some animals on the pial surface at day 1 and with increasing numbers mainly at the edges of the infarcts all days 3 and 7. By day 14 their number had significantly decreased. Subtyping of T lymphocytes revealed that CD4⁺ helper/inducer T cells were rare, while CD8⁺ lymphocytes were abundant. Moreover, CD8⁺ lymphocytes outnumbered CD5⁺ T cells indicating the presence of CD5⁻/CD8⁺ natural killer (NK) cells. ED1⁺ macrophages primarily infiltrated the core of the infarct starting on day 1. Infiltrating leukocytes expressed leukocyte function associated antigen-1 and MHC class I and II antigens. Early after infarction, increased expression of the intercellular adhesion molecule-1 was found on vessel and leukocytes. In conclusion, this study shows that lymphocytes enter the nervous system not only in autoimmune diseases, but also in response to primarily ‘non-immune’ neuronal damage such as stroke.     

Prognosis in middle cerebral artery occlusion

The natural history of MCA occlusion has become increasingly important since the surgical option of EC/IC bypass surgery has been available. The clinical course of 24 patients with angiographically-demonstrated occlusion of the MCA artery was reviewed. Eight patients presented with a major disabling stroke and five of these died during the acute phase of this ischemic event. The remaining 19 patients were followed for a mean of 54.2 months. There were five deaths in follow-up and two of these were due to subsequent strokes. Fourteen patients manifested a benign course: one of these had a further minor stroke and four had TIAs. Altogether, 3 strokes occurred during the follow-up period (2 fatal, 1 minor) and all were in the territory of the artery known to be occluded. Of those patients who survived their presenting ischemic event, 12 (63%) remained completely functional in terms of activities of daily living. MCA occlusion does not necessarily carry a poor prognosis with medial therapy alone and the role of bypass surgery hopefully will be clarified by the ongoing clinically randomized trial.     

Fenofibrate improves cerebral blood flow after middle cerebral artery occlusion in mice

Fibrates, one group of peroxisome proliferator-activated receptor (PPAR) activators, are lipid lowering drugs. Fibrates have been shown to attenuate brain tissue injury after focal cerebral ischemia. In this study, we investigated the impact of fenofibrate on cerebral blood flow (CBF) in male wild type and PPARα-null mice. Animals were treated for 7 days with fenofibrate and subjected to 2 h of filamentous middle cerebral artery occlusion and reperfusion under isoflurane anesthesia. Cortical surface CBF was measured by laser speckle imaging. Regional CBF (rCBF) in nonischemic animals was measured by ¹⁴C-iodoantipyrine autoradiography. Fenofibrate did not affect rCBF and mean arterial blood pressure in nonischemic animals. In ischemic animals, laser speckle imaging showed delayed expansions of ischemic area, which was attenuated by fenofibrate. Fenofibrate also enhanced CBF recovery after reperfusion. However, such effects of fenofibrate on CBF in the ischemic brain were not observed in PPARα-null mice. These findings show that fenofibrate improves CBF in the ischemic hemisphere. Moreover, fenofibrate requires PPARα expression for the cerebrovascular protective effects in the ischemic brain.     

Brain tissue osmolality after middle cerebral artery occlusion in cats

Brain tissue osmolality was measured in cats 2 h after permanent middle cerebral artery occlusion. Blood osmolality was deliberately varied by various therapeutic procedures from 306 to 375 mosm. Osmolality of the blood, the spinal fluid, and both ischemic and nonischemic brain tissue were well equilibrated but there were consistent differences between the various compartments: ischemic tissue osmolality (342 ± 22 mosm, mean ± SD) was about 15 mosm higher than that of nonischemic tissue (327 ± 23 mosm), and cerebral spinal fluid osmolality (333 ± 18 mosm) was 6 mosm higher than nonischemic but 9 mosm lower than ischemic brain tissue. A direct correlation existed between tissue osmolality and brain water, and inverse correlations with electroencephalogram (EEG) intensity, the size of the extracellular space, and the ratio of Na:K concent of ischemic brain tissue. Ischemic brain water increase could be prevented by either increasing blood flow to more than 25 ml 100 g⁻¹ min⁻¹ or by increasing blood osmolality above 335 mosm/liter.