BACKGROUND AND PURPOSE: This study investigated if acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage (GMH). METHODS: Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in P7 rat pups to induce GMH. GMH animals received either deferoxamine or vehicle twice a day for 7 consecutive days. Deferoxamine administration was initiated at either 1 hour or 72 hours post-GMH. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests between day 21 to 28 post-GMH. At 28 days post-GMH, brain morphology was assessed and extracellular matrix protein (fibronectin and vitronectin) expression was determined. RESULTS: Acute and delayed deferoxamine treatment improved long-term motor and cognitive function at 21 to 28 days post-GMH. Attenuated neurofunction was paralleled with improved overall brain morphology at 28 days post-GMH, reducing white matter loss, basal ganglia loss, posthemorrhagic ventricular dilation, and cortical loss. GMH resulted in significantly increased expression of fibronectin and vitronectin, which was reversed by acute and delayed deferoxamine treatment. CONCLUSIONS: Acute and delayed deferoxamine administration ameliorated long-term sequelae after GMH.
BACKGROUND AND PURPOSE: This study investigated if acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage (GMH). METHODS: Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in P7 rat pups to induce GMH. GMH animals received either deferoxamine or vehicle twice a day for 7 consecutive days. Deferoxamine administration was initiated at either 1 hour or 72 hours post-GMH. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests between day 21 to 28 post-GMH. At 28 days post-GMH, brain morphology was assessed and extracellular matrix protein (fibronectin and vitronectin) expression was determined. RESULTS: Acute and delayed deferoxamine treatment improved long-term motor and cognitive function at 21 to 28 days post-GMH. Attenuated neurofunction was paralleled with improved overall brain morphology at 28 days post-GMH, reducing white matter loss, basal ganglia loss, posthemorrhagic ventricular dilation, and cortical loss. GMH resulted in significantly increased expression of fibronectin and vitronectin, which was reversed by acute and delayed deferoxamine treatment. CONCLUSIONS: Acute and delayed deferoxamine administration ameliorated long-term sequelae after GMH.
Authors: Tim Lekic; Anatol Manaenko; William Rolland; Paul R Krafft; Regina Peters; Richard E Hartman; Orhan Altay; Jiping Tang; John H Zhang Journal: Exp Neurol Date: 2012-04-15 Impact factor: 5.330
Authors: Damon Klebe; Jerry J Flores; Devin W McBride; Paul R Krafft; William B Rolland; Tim Lekic; John H Zhang Journal: J Cereb Blood Flow Metab Date: 2016-12-20 Impact factor: 6.200
Authors: Damon Klebe; Devin McBride; Paul R Krafft; Jerry J Flores; Jiping Tang; John H Zhang Journal: J Neurosci Res Date: 2019-02-21 Impact factor: 4.164
Authors: William B Rolland; Paul R Krafft; Tim Lekic; Damon Klebe; Julia LeGrand; Abby Jones Weldon; Liang Xu; John H Zhang Journal: J Neurochem Date: 2017-02-02 Impact factor: 5.372
Authors: Jerry J Flores; Damon Klebe; William B Rolland; Tim Lekic; Paul R Krafft; John H Zhang Journal: Neurobiol Dis Date: 2015-12-29 Impact factor: 5.996