IMMUNOCYTOCHEMICAL EXPRESSION OF THE BLOOD-BRAIN-BARRIER GLUCOSE-TRANSPORTER (GLUT-1) IN NEURAL TRANSPLANTS AND BRAIN WOUNDS

The present study examined the immunocytochemical expression of the bl ood-brain barrier glucose transporter (GLUT-1) in a series of fetal ne ocortical transplants, autonomic tissue transplants, and stab wounds t o the rat brain. GLUT-1 is one of a family of different glucose transp orters and is found exclusively on barrier-type endothelial cells. In the brain it is responsible for the regulated facilitative diffusion o f glucose across the blood-brain barrier. This investigation is the fi rst to determine if this important molecule is altered during the proc ess of angiogenesis that occurs following neural transplantation proce dures or direct brain injury. Beginning in late fetal brain, e.g., E18 and continuing into maturity, GLUT-1 was strongly and exclusively exp ressed on normal cerebral vessels. In solid fetal central nervous syst em (CNS) transplants up to around 3 weeks postoperative, GLUT-1 was on ly weakly expressed, particularly as exemplified by colloidal gold imm unostaining when compared with the host. At later times examined, up t o 15 months postoperative, GLUT-1 immunoexpression was comparable with the normal adjacent brain. In autonomic tissue transplants, where the vessels do not have a blood-brain barrier, as expected, GLUT-1 was no t expressed. In stab wounds, at I week there was extensive gliosis, an d the injured vessels appeared fragmented and collapsed but still expr essed GLUT-1, although to a somewhat lesser extent than normal brain. Between 3 and 6 weeks, GLUT-1 was expressed on tortuous vessels and in apparently fibrillar processes in the wound vicinity with a similar p attern to astrocyte (GFAP) reactivity. These results suggest the occur rence of a down-regulation of GLUT-1 in early transplants, perhaps rel ated to reduced glycolytic activity or transient ischemia, or possibly due to the utilization of alternative energy sources. That GLUT-1 exp ression was not entirely lost in stab wounds to the mature brain sugge sts that the protein may be more labile in fetal or perinatal brain th an in the adult and may not be affected by direct injury. Coupled with previous transplantation studies that have shown reduced neuronal gly colysis and potential barrier alterations, the reduction of GLUT-1 act ivity within nearly the identical time frame could indicate a relative ly early critical period in cellular metabolism following transplantat ion of CNS tissue. (C) 1994 Wiley-Liss, Inc.