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Journal of Neurosurgical Sciences 2001 March;45(1):7-14

language: English

Neuroprotective ­effect of recom­bi­nant ­human eryth­ro­poie­tin in experi­men­tal sub­arach­noid hem­or­rhage

Grasso G.

Department of Neurosurgery, University of Messina, Messina, Italy


Background. Acute cere­bral vaso­con­stric­tion and sub­se­quent ­brain ische­mia, ­often occur­ring in the ear­ly ­phase of sub­arach­noid hem­or­rhage (SAH), are crit­i­cal prob­lems in the man­age­ment of ­patients affect­ed by rup­tured intra­cra­ni­al aneu­rysms. It is ­known ­that ­nitric ­oxide (NO) decreas­es dur­ing SAH ­with impair­ment of cereb­ro­vas­cu­lar relax­a­tion, and glu­ta­mate is main­ly ­involved in the con­se­quent ­brain ischem­ic dam­age. Recently, eryth­ro­poie­tin (EPO) has ­shown to ­exert a neu­ro­pro­tec­tive ­effect dur­ing cere­bral ische­mia by enhanc­ing the NO ­system activ­ity. In the ­present ­study the ­effect of system­ic admin­is­tra­tion of recom­bi­nant ­human eryth­ro­poie­tin (rHuEPO) has ­been inves­ti­gat­ed in a rab­bit mod­el of SAH.
Methods. Thirty-two rab­bits ­were ­assigned to ­four ­groups: 1) Control; 2) SAH; 3) SAH ­plus pla­ce­bo; 4) SAH ­plus rHuEPO. Experimental SAH was ­induced by inject­ing autol­o­gous ­blood ­into the cis­ter­na mag­na. rHuEPO, at a ­dose of 1000 IU/kg, and pla­ce­bo ­were giv­en 5 min­utes ­after SAH. Administration was repeat­ed ­three ­times dur­ing 24 ­hours. The ani­mals ­were ­killed 24 ­hours ­after SAH by a per­fu­sion-fix­a­tion meth­od. Luminal ­cross-sec­tions of the bas­i­lar ­artery ­were meas­ured by com­put­er-assist­ed mor­pho­met­ric anal­y­sis. Ischemic inju­ry was his­to­log­i­cal­ly eval­u­at­ed by anal­y­sis of the fre­quen­cy of ische­mia-­induced dam­aged cor­ti­cal neu­rons.
Results. Administration of rHuEPO sig­nif­i­cant­ly ­reversed the vaso­con­stric­tion of the bas­i­lar ­artery in Group 4 com­pared ­with the oth­er ­groups (p<0.05). Histological exam­ina­tion ­showed a sig­nif­i­cant reduc­tion in ­total dam­aged neu­rons ­count in Group 4 com­pared ­with the oth­er ­groups (p<0.01).
Conclusions. These ­results sug­gest ­that rHuEPO is effec­tive in atten­u­at­ing ­acute cere­bral vaso­con­stric­tion and ischem­ic ­brain inju­ry fol­low­ing experi­men­tal SAH.

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