The significance of brain temperature in focal cerebral ischemia: histopathological consequences of middle cerebral artery occlusion in the rat.
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The purpose of this study was to determine the effect of selective modulation of brain temperature in the experimental settings of permanent and reversible middle cerebral artery (MCA) occlusion in Sprague-Dawley rats. Three models of proximal MCA occlusion were used, in which the effect of brain-temperature modulations could be studied. These included (a) permanent MCA occlusion with an initial 30-min period of hypotension (30 or 36 degrees C x 4 h), (b) permanent MCA occlusion alone (30, 36, or 39 degrees C x 2 h), and (c) 2 h of reversible MCA occlusion (30, 36, or 39 degrees C x 2 h). In the transient MCA occlusion series, intra- and postischemic cortical blood flow was assessed using a laser-Doppler flowmeter placed over the dorsolateral cortex. After a 3-day survival, all rats were perfusion fixed for histopathological analysis and the determination of infarct volume. In animals with permanent MCA occlusion plus hypotension, no significant difference in infarct volume was demonstrated between the 30 and 36 degrees C groups. In rats with permanent MCA occlusion without hypotension, significant differences in infarct volume were again not demonstrable, but an interaction between infarct area and temperature class was shown by repeated-measures analysis, indicating that hypothermia altered the topographic pattern of the cortical infarct. With 2 h of reversible MCA occlusion, there was a statistically significant reduction in infarct volume in the 30 degrees C group compared to 39 degrees C rats. Although intra- and postischemic CBF were not significantly different among the three temperature groups, the cortical infarct volume was positively correlated with postischemic CBF. The postischemic CBF, in turn, was positively correlated to the intraischemic brain temperature and was negatively correlated to CBF during the ischemic period. These findings demonstrate that moderate manipulations of brain temperature have a greater influence on the resulting cortical infarction in the setting of transient focal ischemia than in the context of permanent vascular occlusion. (+info)
A rare case of partially thrombosed giant serpentine right middle cerebral artery aneurysm presented. A 26 year old man initially presented with headache and 3 months later developed neurological deficit. Various stages of clot with patent residual lumen seen on neuroimaging, led to the diagnosis. Catheter angiography is the investigation of choice for evaluating the location, flow dynamics and extent of the serpentine aneurysm. The patient had embolisation done for the giant serpentine aneurysm. (+info)
Targeting cerebral arteries for gene therapy.
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After the steady progress towards application of gene therapy to cerebral arterial diseases, several applications, including modification of gene expression in cerebral arteries, are now feasible. There are several possible targets for cerebrovascular gene therapy, and numerous studies have tested gene therapy strategies in animal models of cerebrovascular disorders. However, some major obstacles, especially issues of safety, must be overcome before clinical use in humans. Gene therapy for cerebral arterial diseases is still in its infancy, and many basic and preclinical studies are yet to be done in order to develop effective and safe techniques. (+info)
Transcranial color-coded sonography for the detection of middle cerebral artery stenosis.
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OBJECTIVE: The purpose of this study was to validate the accuracy and criteria of transcranial color-coded sonography (TCCS) in detecting severe middle cerebral artery (MCA) stenosis. METHODS: One hundred ninety-three patients with acute ischemic cerebrovascular disease who received both TCCS and magnetic resonance angiography (MRA) examinations were evaluated. Middle cerebral artery stenosis assessed by MRA was graded as follows: grade 0, normal to mild (< 50%); grade 1, focal severe stenosis (> or = 50% and stenotic length within the M1 prebifurcation segment); and grade 2, diffuse severe stenosis (> or = 50% and stenotic length greater than the M1 prebifurcation segment). The peak systolic velocity (Vs) and mean velocity (Vm) of bilateral MCAs were obtained by TCCS. Estimates of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for TCCS relative to MRA. RESULTS: After 46 patients were excluded, 309 MCAs (grade 0, 77.3%; grade 1, 15.5%; and grade 2, 7.1%) were evaluated. The optimal diagnostic accuracy of TCCS for the detection of grade 1 MCA stenosis can be reached if Vs is 140 cm/s or higher or Vm is 90 cm/s or higher (sensitivity, 83.3%; specificity, 91.2%). The optimal diagnostic accuracy of grade 2 MCA stenosis can be obtained if V(s) is lower than 50 cm/s or V(s) is 140 cm/s or higher (sensitivity, 81.8%; specificity, 92.1%). In our study, none of the grade 1 but around half of the grade 2 stenosis showed a low flow velocity pattern. CONCLUSIONS: Transcranial color-coded sonography is reliable in detecting severe MCA stenosis. Except for high flow velocity, the addition of a low cutoff of normal flow velocity in our criteria not only increases the study sensitivity but also enables the identification of around half of diffuse severe MCA stenosis. (+info)
Vascular occlusion sites determine differences in lesion growth from early apparent diffusion coefficient lesion to final infarct.
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BACKGROUND AND PURPOSE: Occlusion of major cerebral arteries is the primary source of tissue damage in ischemic stroke and the target of thrombolytic therapy. We hypothesized that large infarcts in more proximal vascular occlusions correspond with substantially increased ischemic lesions shown on initial apparent diffusion coefficient (ADC) maps. METHODS: Initial ADC lesions in 120 patients with acute ischemic stroke were analyzed within 6 hours of stroke onset. Patients were categorized on the basis of vascular occlusion, as shown on MR angiography. Lesion volumes were determined by using manual delineation (ADC(man)) and a threshold method for ADC values (<550 x 10(-9) mm(2)/s(-1), ADC(<550)). Infarct volumes were analyzed by using T2-weighted (n = 109) or CT (n = 11) images obtained on days 5-8. RESULTS: Median lesion volumes for ADC(<550), ADC(man), and infarcts, respectively, were as follows: proximal internal carotid artery (ICA)/middle cerebral artery (MCA) occlusions, 10, 23, and 32 cm(3); carotid-T occlusions, 11, 37, and 138 cm(3); MCA trunk occlusions, 11, 27, and 44 cm(3)); and MCA branch occlusions 8, 27, and 21 cm(3). Initial ADC lesion volumes were different only between the carotid T and the MCA branch (P < .05). On days 5-8, infarct volumes decreased from proximal to distal sites (P < .05), with the exception of MCA trunk versus proximal ICA/MCA occlusions. Recanalization rate in carotid-T occlusion was significantly lower than those of all other occlusion types. CONCLUSION: Initial ADC lesions can be small, even in patients with proximal vascular occlusions. These patients develop considerably large infarctions, suggesting a high potential for infarct growth. This growth might be averted with improved early recanalization of proximal vascular occlusions. (+info)
Ion changes in spreading ischaemia induce rat middle cerebral artery constriction in the absence of NO.
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In rats, cortical spreading hyperaemia is coupled to a spreading neuroglial depolarization wave (spreading depression) under physiological conditions, whereas cortical spreading ischaemia is coupled to it if red blood cell products are present in the subarachnoid space. Spreading ischaemia has been proposed as the pathophysiological correlate of the widespread cortical infarcts abundantly found in autopsy studies of patients with subarachnoid haemorrhage. The purpose of the present study was to investigate whether the extracellular ion changes associated with the depolarization wave may cause the vasoconstriction underlying spreading ischaemia. We induced spreading ischaemia in vivo with the nitric oxide (NO) scavenger oxyhaemoglobin and an elevated K+ concentration in the subarachnoid space while slow potential, pH, extracellular volume and concentrations of K+, Na+, Ca2+ and Cl- were measured in the cortex with microelectrodes. We then extraluminally applied an ionic cocktail (cocktail(SI)) to the isolated middle cerebral artery in vitro, matching the ionic composition of the extracellular space as measured during spreading ischaemia in vivo. Extraluminal application of cocktail(SI) caused middle cerebral artery dilatation in the absence and constriction in the presence of NO synthase inhibition in vitro, corresponding with the occurrence of spreading hyperaemia in the presence and spreading ischaemia in the absence of NO in vivo. The L-type Ca2+ inhibitor nimodipine caused the cocktail(SI)-induced vasoconstriction to revert to vasodilatation in the absence of NO in vitro similar to the reversal of spreading ischaemia to spreading hyperaemia in response to nimodipine in vivo. We found that K+ was the predominant vasoconstrictor contained in cocktail(SI). Its vasoconstrictor action was augmented by NO synthase inhibition. Our results suggest that, under elevated baseline K+ as a hallmark of any condition of energy deficiency, the extracellular ion changes represent the essential mediator of the vascular response to spreading neuroglial depolarization. In the presence of NO they mediate vasodilatation and in its absence they mediate constriction. (+info)
Transformation of diffuse beta-amyloid precursor protein and beta-amyloid deposits to plaques in the thalamus after transient occlusion of the middle cerebral artery in rats.
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BACKGROUND AND PURPOSE: The present study examined the long-term presence of beta-amyloid precursor protein (APP) and beta-amyloid (Abeta) accumulation in the rat thalamus after focal cerebral ischemia. METHODS: Male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 hours. Sensorimotor outcome was assessed using a tapered/ledged beam-walking task after operation. The distribution of APP and Abeta was examined immunohistochemically at 1 week, 1 month, and 9 months after MCAO. RESULTS: MCAO caused a long-lasting deficit in forelimb and hind limb function assessed using the beam-walking test. Histologic examination revealed a transient increase in APP and Abeta staining in axons in the corpus callosum and in neurons at the border of the ischemic region. APP and Abeta deposits persisted in the thalamic nuclei (ventroposterior lateral and ventroposterior medial nuclei), eventually leading to dense plaque-like deposits by the end of the 9-month follow-up. The deposits were surrounded by an astroglial scar. The deposits were positive for Abeta and N-terminal APP, but not for C-terminal APP. Antibodies against the C-terminal of Abeta, ie, Abeta42 and Abeta40, showed a preferential staining for Abeta42. Congo red or thioflavine S did not stain the deposits. CONCLUSIONS: The present results demonstrated the persistent presence and aggregation of APP and Abeta, or their fragments, to dense plaque-like deposits in the ventroposterior lateral and ventroposterior medial nuclei of rats subjected to focal cerebral ischemia. (+info)
Expression of pro-inflammatory and anti-inflammatory cytokines in brain of atherosclerotic rats and effects of Ginkgo biloba extract.
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AIM: To study the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in the brain of rats with atherosclerosis (AS) and the effects of Ginkgo biloba extract (GbE) on expressions of cytokines. METHODS: The experimental model of AS in rats were established by intraperitioneal injection of vitamin D3 with high fat/cholesterol diet. GbE 100 mg/kg was administered to rats by ig. After 8 weeks, the expressions of IL-1beta, TNF-alpha, IL-10, and IL-10R in the brain tissues of AS rats were detected by enzyme-linked immunosorbant assay, immunohistochemistry, Western blotting, and reverse transcriptase polymerase chain reaction. RESULTS: The protein and mRNA expressions of IL-1beta, TNF-alpha, and IL-10 in the brains were markedly higher in AS groups than that in control groups (6.11+/-0.15, 1.55+/-0.14, 0.54+/-0.04 ng/g wet weight vs 0.80+/-0.14, 0.33+/-0.09, and 0.33+/-0.02 ng/g wet weight, respectively). The protein and mRNA expressions of IL-1beta and TNF-alpha in the brains were markedly lower in GbE groups (3.82+/-0.54, 0.95+/-0.08 ng/g wet weight) than that in AS groups, the protein and mRNA expressions of IL-10 and IL-10R in the brains were markedly higher in GbE groups (0.85+/-0.06 ng/g wet weight) than that in AS groups. CONCLUSION: GbE inhibited production of pro-inflammatory cytokines IL-1beta and TNF-alpha, but up-regulated the production of anti-inflammatory cytokines, IL-10 and IL-10R in brain, which might be related with its anti-AS actions. (+info)