The goal is to study a new hypothesis of the mechanism which produces """"""""lacunes"""""""" and """"""""lipohyalinosis""""""""; probable misinterpretation of autopsy findings (obtained months or years after the clinical stroke) has led to the concept that lacunes result from """"""""intrinsic small vessel disease"""""""" due to hypertension or diabetes. This misconception continues to have a detrimental effect on patients with this type of stroke, as diagnostic evaluation is often not done, and preventative therapy is often limited to treatment of hypertension and diabetes. Multiple small embolic cerebral infarcts will be studied in aged rats, which are most appropriate to the study of diseases associated with aging. The right carotid artery of aged and young Fisher rats will be irradiated with a laser (632 nm, 200 mW/cm2, 15 minutes) following the intravenous injection of the photosensitizing dye, Photofrin II, 12.5 mg/kg. A non- occlusive thrombus is produced, which embolizes spontaneously, producing multiple small cerebral infarcts acutely, and lacunes chronically. A small portion of embolic infarcts become hemorrhagic; these hemorrhagic areas will be studied by scanning electron microscopy and energy dispersive x-ray microanalysis, to determine whether they calcify. Calcifications occur in chronic (2 weeks or more) infarcts in this rat model. Astrocytic processes will be stained with GFAP to determine whether they enter the calcified area, or whether this physical barrier induces the formation of a glial limitans which may form the wall of a cavity (lacune). The frequency of calcium in association with lacunes, and the percent of calcified lesions which cavitate by 12 weeks, will be determined. Recanilizing platelet emboli will be studied, as lipid laden macrophages accumulate in emboli by 5 days. The """"""""thickened"""""""" vessel wall could actually be a recanalized platelet embolus, with a lipid component which originated in the macrophages. Immunoperoxidase stains for platelets and endothelium may demonstrate a """"""""vessel wall"""""""" composed of platelets, and 2 layers of endothelium, one surrounding the platelets and one forming a lumen within the mass of platelets (original and neo- endothelium). Thus, platelet emboli could produce all the features associated with lacunes, including cavitation and """"""""lipohyalinosis""""""""; lipohyalinosis could be the result of embolization rather than the cause of focal cerebral ischemia. This data would have an important influence on patient care, as diagnostic evaluation for an embolic source would be a high priority in patients with """"""""lacunar"""""""" strokes, and additional potential therapeutic strategies could be considered. The frequency and extent of tissue retraction will be studied, as retraction of cerebral infarcts could alter imaging characteristics, leading to the potential misdiagnosis of Alzheimer's disease in some patients with multi-infarct dementia. Old and young animals will be compared, to study the effect of aging on these processes.
| Zhai, Q H; Futrell, N; Chen, F J (1997) Gene expression of IL-10 in relationship to TNF-alpha, IL-1beta and IL-2 in the rat brain following middle cerebral artery occlusion. J Neurol Sci 152:119-24 |
| Wang, L C; Futrell, N; Wang, D Z et al. (1995) A reproducible model of middle cerebral infarcts, compatible with long-term survival, in aged rats. Stroke 26:2087-90 |
| Wang, D Z; Futrell, N; Taylon, C et al. (1995) Anticoagulation for prevention of cerebral infarcts following subarachnoid hemorrhage. Surg Neurol 44:270-4 |
| Halvorsen, A M; Futrell, N; Wang, L C (1994) Fibrin content of carotid thrombi alters the production of embolic stroke in the rat. Stroke 25:1632-6 |
| Futrell, N; Riddle, J M (1993) The ultrastructure of photochemically induced thrombi with embolization in a rat model. Stroke 24:1983-91;discussion 1991-2 |
