Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats.
Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and white matter injury in piglets after intracerebral hemorrhage (ICH). In the present study, we examined the effect of deferoxamine on ICH-induced white matter injury and JNK activation and in aged rats. Male Fischer 344 rats (18months old) had either an intracaudate injection of 100μl of autologous blood or a needle insertion (sham). The rats were treated with deferoxamine or vehicle with different regimen (dosage, duration and time window). White matter injury and activation of JNK were examined. We found that a dose of DFX should be at more than 10mg/kg for a therapeutic duration more than 2days with a therapeutic time window of 12h to reduce ICH-induced white matter loss at 2months. ICH-induced white matter injury was associated with JNK activation. The protein levels of phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH-induced JNK activation was reduced by DFX treatment. This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage.
Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Wei
W
Ni
Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Masanobu
M
Okauchi
Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Tetsuhiro
T
Hatakeyama
Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Yuxiang
Y
Gu
Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Richard F
RF
Keep
Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Guohua
G
Xi
Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA. Electronic address: yahua@umich.edu.
Ya
Y
Hua
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000401:mortality; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D056784:Leukoencephalopathies / Q000188:drug therapy* / Q000209:etiology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017262:Siderophores / Q000627:therapeutic use*; D013997:Time Factors
D004676:Myelin Basic Protein; D017262:Siderophores; D048670:MAP Kinase Kinase 4; D003676:Deferoxamine
Deferoxamine; Intracerebral hemorrhage; White matter injury; c-Jun N-terminal kinases