Induction of transient neurological dysfunction in baboons by platelet microemboli

Abstract

Background and purpose: To investigate experimental mechanisms of reversible cerebral dysfunction, we produced transient focal cerebral ischemia in five baboons by unilateral perfusion of internal carotid territories with platelet microemboli generated endogenously.

Methods: Platelet microemboli were formed by incorporating segments of Dacron vascular graft for 1 hour as unilateral carotid arterio-arterial shunts. Platelet embolization was assessed by ultrasonography and isotopic imaging; cerebral function was evaluated by measurements of somatosensory evoked potentials and clinical motor performance.

Results: Platelet microemboli, detected by transcranial Doppler ultrasonography, accumulated rapidly in the shunted carotid hemispheric territory. Indium-111-labeled platelets reached a maximum value of 3.2 +/- 0.8 x 10(9) platelets in the dependent hemisphere of five animals after 20 minutes of carotid blood flow through the grafts when measured in real time by continuous scintillation camera imaging. The retained 111In-platelet microemboli cleared from the cerebral vasculature within 1 hour after removing the grafts. Corresponding blood markers of in vivo thrombus formation, beta-thromboglobulin, platelet factor 4, and fibrinopeptide A, increased eightfold to 20-fold after incorporating graft segments and normalized within 1 hour after removing the grafts. Coincidently, focal neurological function was temporarily impaired, as shown by the ipsilateral loss of somatosensory evoked potentials 5 minutes after initiating platelet microembolization, with restoration 1 hour after removing the grafts in five baboons, and contralateral hemiparesis in two recovered baboons, with complete resolution by 24 hours.

Conclusions: Endogenously generated platelet microemboli accumulate transiently in the dependent cerebral circulation and produce corresponding focal neurological dysfunction that resolves within hours after microembolization.