Chemokine CCL2 induces apoptosis in cortex following traumatic brain injury.
The chemokine C-C motif ligand 2 (CCL2) is an important mediator of neuroinflammation. Released in response to acute injury, ischemia, and neurodegenerative disease, CCL2 binds primarily to the G-protein-coupled chemokine C-C motif receptor 2 (CCR2) to recruit inflammatory cells to sites of tissue damage. Inflammation is thought to have both beneficial and deleterious consequences following traumatic brain injury (TBI), so we investigated CCL2-CCR2 signaling during the post-TBI period to assess possible neurodegenerative and protective actions. Local TBI in adult rat cortex was induced by Feeney's weight-drop method, and the expression of CCL2 and CCR2 in the tissue around the contusion site was measured by real-time quantitative PCR. Both CCL2 and CCR2 mRNA levels were increased markedly for at least 10 days after injury, peaking on day 3. The CCL2 protein was mainly co-localized with the astroglial marker glial fibrillary acidic protein and CCR2 protein with the neuronal nuclear marker NeuN as revealed by double immunofluorescence staining. A selective CCR2 antagonist, RS504393, reduced TUNEL staining, a marker of apoptosis, and improved performance in the Morris water maze 3 days post-TBI, suggesting that CCL2-CCR2 signaling has deleterious effects on neuronal survival and learning. Targeting the CCL2-CCR2 pathway may provide a novel therapeutic approach for the treatment of TBI.
Nanjing Medical University, 140 HanZhong Road, Nanjing, Jiangsu Province, 210029, China.
Su
S
Liu
Lixia
L
Zhang
Qinfeng
Q
Wu
Qi
Q
Wu
Tong
T
Wang
D000818:Animals; D017209:Apoptosis; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018782:Maze Learning; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology / Q000627:therapeutic use
D048588:Benzoxazines; D018932:Chemokine CCL2; D012333:RNA, Messenger; C579117:RS 504393; D054390:Receptors, CCR2; D013141:Spiro Compounds