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  • 1
    ISSN: 1432-1106
    Keywords: Key words Focal cerebral ischemia ; Photothrombosis ; Reperfusion ; Spontaneous recanalization ; Cerebral blood flow ; Edema ; Penumbra ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In clinical thromboembolic stroke, spontaneous late recanalization is a common feature, but one which has been very sparsely studied experimentally. This study aimed at enabling the study of spontaneous reperfusion and exploring its consequences by modifying a recently developed photothrombotic-stroke model that focuses on the region-at-risk located within an ischemic ring-locus. The exposed crania of male Wistar rats (280–340 g) were subjected to a ring-shaped (5.0 mm outer diameter and 0.35 mm thick) laser-irradiation beam (514.5 nm; 0.89 W/cm2) for 2 min simultaneously with intravenous erythrosin B (17 mg/kg) infusion for 30 s. Transcardial carbon-black perfusion experiments revealed a ring-shaped cortical perfusion deficit at 4 h post-irradiation, which progressively increased at 10, 24, and 48 h, at which time the whole region-at-risk was pale with single distal branches of the middle cerebral artery being extensively narrowed, but not occluded. At 72 h, spontaneous reperfusion was observed in the region-at risk, which was even more pronounced at 7 and 28 days. Cortical cerebral blood flow (cCBF), measured by laser-Doppler flowmetry, was distinctly reduced at 2 min post-irradiation and further decreased slightly during 4 h of recording to ca. 24% of baseline values at the ring locus and 40% in the region-at-risk. In the region-at-risk, cCBF flow values were 23–30% of the baseline at 24–48 h post-irradiation, followed by a relative cCBF increase to 71 and 77% at 72 and 96 h post-irradiation. Brain water content in the ischemic part of the cortex increased steadily from 4 to 48 h post-irradiation; at 72 h, it leveled off and returned to control values at 7 days. In conclusion, by employing a laser beam in the shape of a thin ring, critically sustained cCBF reduction was followed by late, consistent spontaneous reperfusion in the region-at-risk in this novel photochemically induced stroke-in-evolution model.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1106
    Keywords: Key words Cerebral ischemia ; focal ; Photothrombosis ; Evolution of ischemia ; Penumbra ; Ischemic cell change ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The photothrombotic ring stroke model with sustained underperfusion followed by late spontaneous reperfusion (Gu et al. 1999) was employed to study its morphological consequences. The exposed crania of adult male Wistar rats were subjected to a ring-shaped laser irradiation beam simultaneously with intravenous erythrosin B infusion. The ischemic volume was calculated from serial sections throughout the ischemic lesions at 4, 10, 24, 48, and 72 h and 7 days and 28 days after irradiation. The ischemic volume, expressed as a percentage of the ipsilateral hemispheric volume, increased steadily from 4 to 10 to 24 h to reach its maximum value at 48 h after irradiation; at 3 days, 7 days, and 28 days, the ischemic volume was reduced to 75%, 24%, and 22% of the value at 48 h. Evaluation of ischemic volumes at different anteroposterior levels revealed that the reduced ischemic volume at 72 h and later was mainly due to morphological restoration in the centrally located, nonirradiated region at risk. An initial enlargement and development of cystic coagulation necrosis was observed in the cortical areas corresponding to the ring lesion itself. In the region at risk, a gradually deteriorating neuropil and nerve cell morphology were observed over time, with maximum severity at 48 h postirradiation. At this time, most laminae II and III neurons in the region at risk exhibited eosinophilia and pyknosis but no incrustations, with small islands of less damaged neurons randomly scattered. At 72 h and up to 28 days after irradiation, these cell characteristics were no longer observed and the region at risk was well populated with neurons that had a chiefly unremarkable cytological appearance. Neuronal counts in the central part of the region at risk were performed; no significant difference in neuronal density was observed between sham-operated controls and at 28 days after irradiation. In conclusion, the consistent, late spontaneous reperfusion coincided with remarkable tissue recovery as assessed morphologically in the region at risk. The data suggest that nerve cell repair may occur even after the detection, by conventional morphological methods, of prolonged critical ischemic neuronal damage in the setting of acute ischemic stroke.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study aimed at evaluating changes in expression of immediate early genes in a new photothrombotic focal ischemia model that exhibits late spontaneous reperfusion and morphological restoration in the region-at-risk within the cerebral cortex. Gene expression was studied with Northern blots, in situ hybridization and immunohistochemistry. At early time points (1–4 h), nerve growth factor-induced gene A and B, and c-fos mRNAs, were quickly induced throughout the ipsilateral cortex, with no obvious differences between the region-at-risk and remote cortical areas. High concentrations of nerve growth factor-induced gene A and c-Fos proteins were present within the region-at-risk even when cortical cerebral blood flow was as low as 40% of control values. At 4 h the nerve growth factor-induced gene A mRNA and protein expression was significantly decreased in the hippocampus vs. naive controls. However, a small decrease was also found in sham-operated and anaesthetized controls. A late induction, at 5 days, of c-fos and nerve growth factor-induced gene B mRNAs was seen bilaterally in the hippocampus and also, in the case of nerve growth factor induced-gene B, in the contralateral cortex. A complex pattern of changes in immediate early gene expression occurs after reversible focal cortical ischemia. This may be important for tissue recovery as well as neuropsychiatric symptoms after stroke.
    Type of Medium: Electronic Resource
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