Abstract:
OBJECTIVE:Inflammatory cascades play a significant role in progressive neurological injury after transient cerebral ischemia. It has been demonstrated that heparin, a potent anticoagulant, also possesses anti-inflammatory properties that diminish postreperfusion damage after stroke. However, the potential for heparin to induce hemorrhagic transformation of an infarct has deterred its use in cases of focal cerebral ischemia. In this study, we examined whether or not administration of a novel O-desulfated heparin (ODSH), with significantly decreased anticoagulant activity but active anti-inflammatory effects, would ameliorate inflammatory neurological injury without increasing intracerebral hemorrhage in a rat model of transient middle cerebral artery occlusion. METHODS:Rats were injected immediately before ischemia with phosphate-buffered saline or ODSH (5 mg/kg, intravenously) and then every 12 hours (15 mg/kg, subcutaneously) for 72 hours. The animals were assessed for neurological function using a foot fault test and modified Bederson scale on Days 1, 2, and 5; plasma samples were analyzed for activated clotting time at multiple time points after the initial ODSH dose. After sacrifice on Day 5, infarct volume was determined and brain tissue was examined for evidence of hemorrhage both grossly and using a previously validated spectrophotometric hemoglobin assay. RESULTS:ODSH-treated animals demonstrated significantly improved foot fault performance (P = 0.03) on Day 5 and reduced stroke volumes (P = 0.03) relative to controls. Although the brains of ODSH-treated rats exhibited significantly higher hemoglobin levels in a standardized assay (P = 0.01), there were no incidences of gross hemorrhage observed in either group, and activated clotting time measurements for the treated animals were not significantly elevated over baseline at any time point. CONCLUSION:Our findings indicate that ODSH can be administered at a dose that provides postischemic anti-inflammatory neuroprotection without an increased risk of intracerebral hemorrhage.
journal_name
Neurosurgeryjournal_title
Neurosurgeryauthors
Mocco J,Shelton CE,Sergot P,Ducruet AF,Komotar RJ,Otten ML,Sosunov SA,Macarthur RB,Kennedy TP,Connolly ES Jrdoi
10.1227/01.neu.0000306109.55174.e6subject
Has Abstractpub_date
2007-12-01 00:00:00pages
1297-303; discussion 1303-4issue
6eissn
0148-396Xissn
1524-4040pii
00006123-200712000-00021journal_volume
61pub_type
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