Dysbaric injury of rat's central nervous system: The role of microglia / 第二军医大学学报

ABSTRACT

Objective: To observe the change of microglia activity after fast decompressing and/or hyperbaric oxygenation (HBO)-induced central nervous system (CNS) damage, so as to study the role of microglia in CNS dysbaric injury and the effects of HBO on microglia. Methods: Rats were randomly divided into the following groups: normal control, safe decompressing, fast decompressing (FD) injured, and HBO treated groups. Rat models of dysbaric injury were established by FD; 6 h later the rat models were subjected to HBO treatment. The activated microglia were detected by FITC-linked Isolectin B4; TNF-α and TNF-α converting enzyme (TACE) positive cells were detected immunohistochernically; and neural apoptosis was detected by TUNEL assay. TNF-α contents in CNS tissue were determined by ELISA and the bioactivity of sTNF-α in cerebrospinal fluid (CSF) were determined by L929 cell cytotoxicity bioassay. Results: 1134 positive microglia appeared in rats' CNS 6 h after FD treatment, peaked after 24 h, and declined thereafter. The activated microglia had morphological changes. Cell apoptosis indices of CNS reached its peak 48 h after FD treatment. Activated microglia and apoptotic neurons had similar distribution. TNF-α was detected in the brain and spinal cord 6 h after FD, significantly increased after 24 h, and peaked after 48 h. The content of TNF-α was positively correlated with IB4 positive cells and apoptosis index (P<0.05). TNF-α bioactivity in CSF of FD group had a similar change to TNF-α content in CNS tissue. The IHC results showed that, TNF-α and TACE positive cells had the same morphology and distribution to those of IB4 positive cells. HBO treatment significantly decreased IB4 positive cells after 24 h, 48 h, and 72 h; reduced TNF-α content in CNS tissues and TNF-α cytotoxicity in CSF; and decreased the apoptosis index after 48 h and 72 h. Conclusion: Microglial cells are quickly activated after dysbaric-induced injury of CNS. The activated microglia play a role in secondary injury through increasing TNF-α and TACE expression. HBO therapy can protect the neurons through depressing the activation and proliferation of microglia and reducing secretion of neurotoxin.