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Citicoline treatment for experimental intracerebral hemorrhage in mice
W Clark1, L Gunion-Rinker, N Lessov
1Oregon Stroke Center, Oregon Health Sciences University, Portland, Oregon 97201 clarkw@ohsu.edu
Insights
Citicoline sodium treatment improved neurological function and reduced ischemic brain injury in an experimental intracerebral hemorrhage model. This neuroprotective effect suggests potential for citicoline in treating human ICH.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Citicoline sodium is known to mitigate ischemic injury in the central nervous system.
- Intracerebral hemorrhage (ICH) is characterized by a hematoma and surrounding ischemic/edematous tissue.
- Neuroprotective therapies may reduce injury associated with ICH.
Purpose of the Study:
- To evaluate the efficacy of citicoline sodium in reducing ischemic injury.
- To assess the impact of citicoline sodium on functional neurological outcomes in an ICH model.
Main Methods:
- Intracerebral hemorrhage was induced in 68 Swiss albino mice using collagenase injection.
- Mice received either citicoline sodium (500 mg/kg) or saline IP before collagenase and at 24, 48 hours.
- Neurological function was assessed using a 28-point scale; brain tissue was analyzed for hematoma and ischemic volumes at 54 hours.
Main Results:
- Citicoline-treated mice demonstrated significantly improved neurological scores compared to placebo (10.4 vs. 12.1, P<0.01).
- Hematoma volumes did not differ between groups.
- Citicoline treatment resulted in a smaller volume of surrounding ischemic injury (13.8 mm³ vs. 17.0 mm³, P<0.05).
Conclusions:
- Citicoline sodium significantly enhanced functional outcomes in an animal model of ICH.
- Treatment with citicoline sodium effectively reduced the extent of ischemic injury surrounding the hematoma.
- These findings support the potential therapeutic application of citicoline in managing human intracerebral hemorrhage.
Background And Purpose:
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.