Title |
Minocycline-Suppression of Early Peripheral Inflammation Reduces Hypoxia-Induced Neonatal Brain Injury
|
---|---|
Published in |
Frontiers in Neuroscience, September 2017
|
DOI | 10.3389/fnins.2017.00511 |
Pubmed ID | |
Authors |
Yingjun Min, Hongchun Li, Kaiyu Xu, Yilong Huang, Jie Xiao, Weizhou Wang, Longjun Li, Ting Yang, Lixuan Huang, Ling Yang, Hong Jiang, Qian Wang, Min Zhao, HaiRong Hua, Rong Mei, Fan Li |
Abstract |
While extensive studies report that neonatal hypoxia-ischemia (HI) induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d) rat pups to systemic hypoxia (3.5 h), a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg) was injected intraperitoneally (i.p.) 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg) minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS), indicated by presence of C-C chemokine receptor type 2 (CCR2(+))/CD11b(+)CD45(+) positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker). Interrupted blood-brain barrier (BBB), hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 3 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 24 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 3 | 13% |
Student > Ph. D. Student | 3 | 13% |
Student > Doctoral Student | 2 | 8% |
Student > Bachelor | 2 | 8% |
Student > Postgraduate | 2 | 8% |
Other | 4 | 17% |
Unknown | 8 | 33% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 5 | 21% |
Medicine and Dentistry | 4 | 17% |
Psychology | 2 | 8% |
Nursing and Health Professions | 1 | 4% |
Agricultural and Biological Sciences | 1 | 4% |
Other | 1 | 4% |
Unknown | 10 | 42% |