Studies on the Cellular Responses and Roles of Microglia, Astrocytes, and Blood-Derived Inflammatory cells in Injured Rat Brain

Brain inflammation is accompanied by brain injury. For several decades, brain inflammation has been considered toxic to the brain. However, recent studies also suggest beneficial roles of inflammation in injured brain. In this study, I analyzed patterns and roles of brain inflammation in injured brain in vivo from the early stage of the injury to have answers to the question whether brain inflammation is harmful and beneficial. In the first part of this study, acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc) and the cortex of the rat brain. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h, and monocytes filled the damaged core after neurons and microglia died. Neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (~80% of that in the contralateral side) did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. Thus, the inflammatory responses of microglia and monocytes in response to ATP-induced acute injury may not be neurotoxic. In the second part, I examined behavior and roles of infiltrated monocytes in LPS-injected SNpc. Monocytes vigorously infiltrated at 3 d and thereafter gradually decreased. Some of infiltrated monocytes died, and the remaining monocytes changed morphologically from round to ramified ones. Monocytes exert alternatively activated phenotypes: strong expression of phagocytic activity but negligible expression of pro-inflammatory mediators such as TNF-α, IL-1β and iNOS. Accordingly, recovery of impaired astrocytes, endothelial cells, and neuronal cells occurred after monocytes infiltrated. These results indicate that monocytes play important roles to repair of the injured brain. In the third part, it has been examined how systemic inflammation (SI) affected brain inflammation. After the induction of SI, in the SN region, microglia were morphologically activated, neutrophils infiltrated, and mRNA/protein expression of inflammatory mediators increased within 4-8 h, and subsided within 1-3 days. However, dopaminergic neuronal loss was not detectable for up to 8 d after induction of SI. These results indicate that acute systemic inflammation causes brain inflammation, but this is not sufficiently toxic to induce neuronal injury. Taken together, these results in the three models suggest that brain inflammation functions to isolate damaged sites, remove dead cells and debris, and repair microenvironment of the brain rather than to produce cytotoxic proinflammatory mediators. Therefore, brain inflammation appears to be beneficial rather than detrimental to injured brain.

Author dc:creator

• 정, 혜경

Contributors dc:contributor

• 조, 은혜
• 대학원 의학과
• 200624325

• 신경교세포
• 혈액염증세포
• 뇌 손상
• Microglia
• Astrocytes
• Blood-Derived Inflammatory Cells
• Brain Inflammation

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000011241
000000011241

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/4330