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Background and Purpose-Although pathophysiological studies of focal cerebral ischemia in nonhuman primates can provide important information not obtainable in rodent models, primate experimentation is limited by considerations of cost, availability, effort, and ethics. A reproducible and quantitative model that minimizes the number of animals necessary to detect differences between treatment groups is therefore crucial. Methods-Eight male baboons (weight, 22Ϯ2 kg) underwent left transorbital craniectomy followed by 1 hour of temporary ipsilateral internal carotid artery occlusion at the level of the anterior choroidal artery together with bilateral temporary occlusion of both anterior cerebral arteries (A1) proximal to the anterior communicating artery. A tightly controlled nitrous oxide-narcotic anesthetic allowed for intraoperative motor evoked potential confirmation of middle cerebral artery (MCA) territory ischemia. Animals survived to 72 hours or 10 days if successfully self-caring. Outcomes were assessed with a 100-point neurological grading system, and infarct volume was quantified by planimetric analysis of both MRI and triphenyltetrazolium chloride-stained sections. Results-Infarction volumes (on T2-weighted images) were 32Ϯ7% (meanϮSEM) of the ipsilateral hemisphere, and neurological scores averaged 29Ϯ9. All animals demonstrated evidence of hemispheric infarction, with damage evident in both cortical and subcortical regions in the MCA vascular territory. Histologically determined infarction volumes differed by Ͻ3% and correlated with absolute neurological scores (rϭ0.9, Pϭ0.003). Conclusions-Transorbital temporary occlusion of the entire anterior cerebral circulation with strict control of physiological parameters can reliably produce reperfused MCA territory infarction. The magnitude of the resultant infarct with little interanimal variability diminishes the potential number of animals required to distinguish between 2 treatment regimens. The anatomic distribution of the infarct and associated functional deficits offer comparability to human hemispheric strokes. (Stroke. 2000;31:3054-3063.)

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Abstract-Although inhibiting interaction of ␤ 2 integrins with cognate immunoglobulin class adhesion receptor ligands is an effective neuroprotective strategy in small mammal models of stroke, the strategy has failed in human trials. A completely different antiadhesion receptor strategy was therefore rigorously tested in a model that may more closely approximate human reperfused stroke. Early leukoadhesive events in postischemic cerebral microvessels are mediated by upregulated selectin-class adhesion receptors on endothelial cells. Therefore, a blocking antibody prepared against common P-and E-selectin epitopes was humanized to suppress complement activation and tested in a reperfused hemispheric stroke model in Papio anubis (baboon). Histological examination of postischemic cerebral microvessels revealed a strong upregulation of E-and P-selectin expression. Placebo-blinded administration of the humanized anti-human E-and P-selectin monoclonal antibody (HuEP5C7, 20 mg/kg IV, nϭ9; placebo, nϭ9) immediately after the onset of 1 hour of temporary ischemia resulted in trends showing reduced polymorphonuclear leukocyte (PMN) infiltration into ischemic cortex, reduced infarct volumes (by 41%), improved neurological score (by 35%), and improved ability to self-care (by 39%). Importantly, there was no evidence of systemic complement activation, immune suppression, or pathological coagulopathy associated with this therapy. These data suggest that a humanized anti-E/P-selectin antibody approach is safe and may be effective as a clinical treatment for human stroke.

The antiseptic-impregnated catheters prevented bacterial adherence and biofilm formation and produced no local or systemic toxicity.

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The purpose of this study was to investigate the expression of the immediate early gene, c-fos, in GnRH neurons in female rhesus monkeys as a function of generation of the LH surge. Adult monkeys were either intact (n = 6) or ovariectomized (n = 10). Intact animals received estradiol benzoate (EB; 330 micrograms in oil, sc; n = 5) or oil (n = 1). Ovariectomized animals received either EB (n = 5) or EB, followed by progesterone (P; 2.5 ml in oil, im; n = 4), or oil (n = 1). Animals were killed from 31-75 h after EB treatment. Blood samples were collected to document LH release in response to steroid treatment. A surge of LH was initiated in most animals that received EB alone or EB plus P about 30 h after steroid treatment. Animals were perfused with 4% paraformaldehyde, and brain blocks encompassing the region known to contain the majority of GnRH neurons (septum through the medial basal hypothalamus) were cut on the vibratome. Sites of FOS and GnRH immunoreactivities were demonstrated using double labels with a variety of chromogens. Regardless of the time in the surge, there were very few GnRH neurons with FOS immunoreactivity in their nuclei (0-9%). FOS-positive nuclei were seen in many other neurons in various brain regions, including the suprachiasmatic and supraoptic nuclei. There were no differences in FOS expression in GnRH neurons in intact and ovariectomized animals or in steroid- or oil-treated animals. These results suggest that FOS activation in GnRH neurons is not associated with the initiation of the secretory GnRH stimulus to the LH surge in the rhesus monkey. If confirmed, these data suggest that the GnRH nerve terminal may be the primary site for the control of the GnRH surge.