UPTAKE OF PLASMA-PROTEINS INTO DAMAGED NEURONS - AN EXPERIMENTAL-STUDY ON CRYOGENIC LESIONS IN RATS

Preliminary observations on human autopsy material have indicated that damaged neurons may take up plasma proteins early after the injury. These observations prompted an experimental study under controlled conditions. Focal brain lesions were produced in rats by extracranial application of dry ice for 90 s. This caused an immediate disruption of the blood-brain barrier with leakage of plasma components into the tissue and sharply circumscribed areas of necrosis of the underlying cortex. Five minutes after the lesions, uptake of albumin, fibrinogen and fibronectin into damaged neurons was demonstrated by immunostains. These proteins were retained in the injured neurons until they were phagocytized 2-4 days later. In addition, normal neurons whose axons or axon collaterals passed through or terminated in the lesion were labeled. This labeling was generally weaker than in damaged neurons and no labeling of neuronal nuclei was observed in these cells in contrast to those of damaged cells. Apart from nerve cells labeled through retrograde axonal transport, no staining of normal neurons was observed. Intravenous injections of Evans blue, which binds to plasma proteins, confirmed that albumin was taken up to into damaged neurons almost immediately after the injury and showed that this uptake continued for at least 20 h. It is concluded that uptake of plasma proteins into damaged neurons may serve as early (and late) markers of neuronal injury.