Modulation of parietal cytokine and chemokine gene profiles by mesenchymal stem cell as a basis for neurotrauma recovery

Abstract

Background & purpose: Following traumatic brain injury (TBI), primary mechanical injury to the brain may cause blood-brain-barrier damage followed by secondary injury, ultimately culminating in cell death. We aimed to test whether one injection of mesenchymal stem cells (MSC) derived from the human umbilical cord can modulate brain cytokine and chemokine gene profiles and attenuate neurological injury in rats with TBI. Methods: One-day post-TBI, the injured rats were treated with one injection of MSC (4 × 106/rat, i.v.). Three days later, immediately after assessment of neurobehavioral function, animals were sacrificed for analysis of neurological injury (evidenced by both brain contusion volume and neurological deficits) and parietal genes encoding 84 cytokines and chemokines in the injured brain by qPCR methods. Results: Three days post-TBI, rats displayed both neurological injury and upgrade of 11 parietal genes in the ipsilateral brain. One set of 8 parietal genes (e.g., chemokine [C-X-C motif] ligand 12, platelet factor 4, interleukin-7, chemokine [C-C motif] ligand (CCL)19, CCL 22, secreted phosphoprotein 1, pro-platelet basic protein 1, and CCL 2) differentially upgraded by TBI was related to pro-inflammatory and/or neurodegenerative processes. Another set of 3 parietal genes up-graded by TBI (e.g., glucose-6-phosphate isomerase, bone morphogenetic protein (BMP) 2, and BMP 4) was related to anti-inflammatory/neuroregenerative events. Administration of MSC attenuated neurological injury, down-regulated these 8 parietal pro-inflammatory genes, and up-regulated these 3 parietal anti-inflammatory genes in the rats with TBI. Conclusion: Our data suggest that modulation of parietal cytokines and chemokines gene profiles by MSC as a basis for neurotrauma recovery. Keywords: Mesenchymal stem cells, Traumatic brain injury, Inflammation, Chemokines, Cytokines