HYPERTHERMIA INDUCES ULTRASTRUCTURAL-CHANGES IN MOUSE PIAL MICROVESSELS

Background: Pial microvessels' responses to local hyperthermia reveale d the development of in vivo spontaneous thrombosis. The cellular and subcellular changes which contribute to such events remained unexplore d. Therefore, the effect of regional hyperthermia (43 degrees C) on mo use pial microvessels was studied at the ultrastructural level. Method s: A simple cranial window assembly, including an artificial cerebrosp inal fluid delivery and heating system to ensure a precise brain regio nal temperature, was used. The animal core body temperature was mainta ined at 37 degrees C. Topical and transvessel bimodal fixation of micr ovessels was done with a phosphate buffered mixture of glutaraldehyde and paraformaldehyde, followed by a standard electron microscopy proce dure. Results: When the pial microvessels of control (37 degrees C) an imals were examined, no evidence of cellular damage was discerned. End othelial cells including luminal membrane were unchanged. Degranulated platelets or platelet aggregates were not seen. However, numerous pla telets in association with scattered red blood cells and occasional wh ite blood cells could be observed in a close proximity, but not adhere d, to the endothelial wall of hyperthermic (43 degrees C) brains. Plat elets displayed a variety of forms consistent with the onset of platel et activation. Discoid platelets containing granules and spheroid degr anulated platelets and those with large pseudopodia were recognized. T he venular endothelial surface revealed conspicuous endothelial change , with the presence of endothelial denudation. The site of platelet ag gregation in both venules and arterioles was accompanied by focal endo thelial lucency and denudation vacuole formation, luminal membrane rup ture, and swelling of the nuclear envelope. Conclusions: These finding s demonstrate the extent of damage to the pial microvasculature in res ponse to a local hyperthermic exposure. The results emphasize that cha nges in the endothelium may represent the earliest signs of oncoming v ascular pathology. (C) 1995 Wiiey-Liss, Inc.