Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats.
OBJECTIVE
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.
Dempsey
Robert J
RJ
Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA. Dempsey@neurosurg.wisc.edu
Raghavendra Rao
Vemuganti L
VL
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000473:pathology; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010740:Phospholipases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003566:Cytidine Diphosphate Choline; D010740:Phospholipases