Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats
Dempsey RJ, Raghavendra Rao VL.
Department of Neurological Surgery,
University of Wisconsin,
Madison, Wisconsin 53792, USA.
J Neurosurg. 2003 Apr;98(4):867-73
ABSTRACTOBJECT: In previous studies at their laboratory the authors showed that cytidinediphosphocholine (CDP-choline), an intermediate of phosphatidylcholine synthesis, decreases edema formation and blood-brain barrier disruption following traumatic brain injury (TBI). In the present study the authors investigate whether CDP-choline protects hippocampal neurons after controlled cortical impact (CCI)-induced TBI in adult rats. METHODS: After adult male Sprague-Dawley rats had been anesthetized with halothane, a moderate-grade TBI was induced with the aid of a CCI device set at a velocity of 3 m/second, creating a 2-mm deformation. Sham-operated rats, which underwent craniectomy without impact served as controls. The CDP-choline (100, 200, and 400 mg/kg body weight) or saline was injected into the animals twice (once immediately postinjury and once 6 hours postinjury). Seven days after the injury, the rats were neurologically evaluated and killed, and the number of hippocampal neurons was estimated by examining thionine-stained brain sections. By 7 days postinjury, there was a significant amount of neuronal death in the ipsilateral hippocampus in the CA2 (by 53 +/- 7%, p < 0.05) and CA3 (by 59 +/- 9%, p < 0.05) regions and a contusion (volume 34 +/- 8 mm3) in the ipsilateral cortex compared with sham-operated control animals. Rats subjected to TBI also displayed severe neurological deficit at 7 days postinjury. Treating rats with CDP-choline (200 and 400 mg/kg, intraperitoneally) significantly prevented TBI-induced neuronal loss in the hippocampus, decreased cortical contusion volume, and improved neurological recovery. CONCLUSIONS: Treatment with CDP-choline decreased brain damage following TBI.DMAE
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