Citicoline treatment for experimental intracerebral hemorrhage in mice.
OBJECTIVE
Citicoline sodium (cytidine-5'-diphosphocholine) has been shown previously to reduce ischemic injury in focal central nervous system models. Intracerebral hemorrhage (ICH) appears to be associated with an area of edema and ischemic injury surrounding the hematoma that may be reduced by neuroprotective therapy. The present study was designed to test whether treatment with citicoline reduces ischemic injury and improves functional neurological outcome in an experimental model of ICH.


METHODS
In 68 Swiss albino mice (26 to 36 g), ICH was induced by collagenase injection into the caudate nucleus. Animals were randomized to receive either: citicoline 500 mg/kg or saline IP prior to collagenase and at 24 and 48 hours. Animals were rated on a 28-point neurological scale and sacrificed at 54 hours. The brains were sectioned, and the volume of hematoma, total lesion, and surrounding ischemic injury was determined.


RESULTS
In terms of functional outcome, animals treated with citicoline had improved neurological outcome scores compared with placebo-treated animals: 10.4+/-2.0 versus 12.1+/-2.4 (P<0.01). Regarding ischemic injury, although there was no difference in the underlying hematoma volumes, animals treated with citicoline had a smaller surrounding volume of ischemic injury than placebo-treated animals: citicoline, 13.8+/-5.8 mm3 (10.8+/-4.3% of hemisphere); placebo, 17.0+/-7.1 mm3 (13.3+/-5. 1%) (P<0.05).


CONCLUSIONS
In this animal model of ICH, treatment with citicoline significantly improved functional outcome and reduced the volume of ischemic injury surrounding the hematoma. This study supports a potential role for citicoline in clinical ICH treatment.
Oregon Stroke Center, Oregon Health Sciences University, Portland, Oregon 97201 clarkw@ohsu.edu
W
W
Clark
L
L
Gunion-Rinker
N
N
Lessov
K
K
Hazel
D000818:Animals; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003566:Cytidine Diphosphate Choline / Q000627:therapeutic use*; D006406:Hematoma / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D009420:Nervous System / Q000187:drug effects / Q000503:physiopathology; D018697:Nootropic Agents / Q000627:therapeutic use*; D016896:Treatment Outcome
D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline