Effect of autologous clot embolism on regional protein biosynthesis of monkey brain.

Abstract

Focal cerebral ischemia was produced in monkeys by injection of autologous clots into the left internal carotid artery. Regional protein synthesis was studied 2 hours after embolism by autoradiographic and biochemical evaluation of [ 1 H]phenylaIanine incorporation into brain proteins, and the results were correlated with electrophysiologic (electroencephalogram, evoked potentials) and light microscopic observations. Ischemic territories were clearly identified on autoradiograms as sharply demarcated areas with reduced radioactivity. The localization of regions with reduced protein biosynthesis correlated with the early postembolic suppression of evoked potentials but not with the (improved) functional state and the morphologic alterations at the end of the experiment. Suppression of amino add incorporation, in consequence, is a long-lasting event that allows documentation of the initial embolic impact for at least 2 hours irrespective of the subsequent recovery process. (Stroke

Endovascular Ischemic Stroke Models in Nonhuman Primates

“…Clot models in NHPs closely mimic the pathogenesis of stroke patients and hold potential for thrombolysis treatment. Thrombus models by endovascular methods are summarized in Table 3 [16,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]. In order to achieve an ideal ischemic stroke model in NHPs using thrombi, 2 key factors are needed: 1) accurate control of thrombus; and 2) timely recanalization of the vessel.…”

“…As reported in rodent models of thromboembolic stroke, the major concern of these models in NHPs is control over the introduced embolus, which may be determined by the site of occlusion and nature of the clot [55]. Such concerns arose when 2 studies reported an experimental thromboembolic model in NHPs in which the clots introduced were not at the injection site but migrated down to a nearby site [48,49]. In order to selectively block the MCA, 1 study combined neurosurgical and endovascular methods in rhesus monkeys [50].…”

Thrombotic Stroke in the Anesthetized Monkey <b><i>(Macaca mulatta)</i></b>: Characterization by MRI – A Pilot Study

“…For instance, in contrast to our present protocol, in models where autologous or heterologous preformed clots are used [22,23,42,43], the precise location of the arterial occlusion is not controlled (proximal or distal, middle or anterior MCA, involvement of the lenticulostriate arteries). In the photothrombotic model [27,28], although the location of the clot is also controlled, concerns have been recently raised about the mechanism involved in clot formation in such models and its relevance in what happens in the ‘real-life situation’ [44].…”

“…Experimental techniques to occlude the middle cerebral artery (MCA) involve mechanical occlusions by using either electrocoagulation [6,7], a filament model [8,9], an intravascular balloon or cuff [2,10,11,12], microvascular clips [13,14,15,16,17,18], or ligatures [19,20,21]. Other approaches use the intravascular route to inject autologous or heterologous preformed fibrin, blood clots [3,22,23], microemboli [24,25,26], or, in some cases, by in situ clot formation by photothrombosis [27,28,29]. However, it is important to establish which, if any, of these models of focal cerebral ischemia can be considered to be the most representative of an acute stroke in humans.…”

Preclinical acute ischemic stroke modeling

“…This caused a heterogeneous pattern of intracranial arterial occlusion in the ACA, MCA and the posterior cerebellar artery territories of one and both hemispheres with variable degrees of alterations in EEG and sensory evoked potentials 26. In addition, this model was not very reliable and often had early spontaneous recanalization and inconsistent occlusions.…”