Reduced cerebral blood flow but elevated cerebral glucose metabolic rate in erythropoietin overexpressing transgenic mice with excessive erythrocytosis

To examine the impact of excessive erythrocytosis on local cerebral blood flow ( CBF) and cerebral glucose metabolic rate (CMRglc), we made use of our constitutively erythropoietin ( Epo)- overexpressing transgenic mouse line ( tg- 6) that reach a mean hematocrit of 0.87. Compared with wildtype ( wt) control siblings, CBF decreased by 44% in tg- 6 mice, while upon hemodilution ( tg- 6- HD) to a physiologic hematocrit ( e. g., 0.44) tg- 6- HD mice returned the CBF to wt levels. Cerebral blood flow was determined in another transgenic mouse line that overexpresses human Epo in the brain only ( tg- 21): CBF increased by 17% compared with wt controls. However, oxygen delivery was similar in all four mouse groups tested ( wt, tg- 6, tg- 6- HD and tg- 21). Mean CMRglc was higher in tg- 6 ( + 72%), tg- 6- HD mice ( + 43%) and tg- 21 ( + 22%) than in wt mice. Local CMRglc was higher in all 40 brain regions in tg- 6 but only in 15 and 8 regions in tg- 6- HD and tg- 21 mice. These results show that prolonged increases in hematocrit did not alter cerebral oxygen delivery at a decreased CBF and increased CMRglc. Hemodilution suggests that high blood viscosity is a cause of the decrease in CBF and partly of the increase in CMRglc. Cerebral glucose metabolic rate may also be increased by a direct effect of Epo in the brain ( tg- 21 mice).