NEUROCRITICAL CARE, vol.36, no.3, pp.802-814, 2022 (SCI-Expanded)
Background Understanding the secondary damage mechanisms of traumatic brain injury (TBI) is essential for developing new therapeutic approaches. Neuroinflammation has a pivotal role in secondary brain injury after TBI. Activation of NLRP3 inflammasome complexes results in the secretion of proinflammatory mediators and, in addition, later in the response, microglial activation and migration of the peripheral immune cells into the injured brain are observed. Therefore, these components involved in the inflammatory process are becoming a new treatment target in TBI. Dexmedetomidine (Dex) is an effective drug, widely used over the past few years in neurocritical care units and during surgical operations for sedation and analgesia, and has anti-inflammatory effects, which are shown in in vivo studies. The aim of this original research is to discuss the anti-inflammatory effects of different Dex doses over time in TBI. Methods Brain injury was performed by using a weight-drop model. Half an hour after the trauma, intraperitoneal saline was injected into the control groups and 40 and 200 mu g/kg of Dex were given to the drug groups. Neurological evaluations were performed with the modified Neurological Severity Score before being killed. Then, the mice were killed on the first or the third day after TBI and histopathologic (hematoxylin-eosin) and immunofluorescent (Iba1, NLRP3, interleukin-1 beta, and CD3) findings of the brain tissues were examined. Nonparametric data were analyzed by using the Kruskal-Wallis test for multiple comparisons, and the Mann-Whitney U-test was done for comparing two groups. The results are presented as mean +/- standard error of mean. Results The results showed that low doses of Dex suppress NLRP3 and interleukin-1 beta in both terms. Additionally, high doses of Dex cause a remarkable decrease in the migration and motility of microglial cells and T cells in the late phase following TBI. Interestingly, the immune cells were influenced by only high-dose Dex in the late phase of TBI and it also improves neurologic outcome in the same period. Conclusions In the mice head trauma model, different doses of Dex attenuate neuroinflammation by suppressing distinct components of the neuroinflammatory process in a different timecourse that contributes to neurologic recovery. These results suggest that Dex may be an appropriate choice for sedation and analgesia in patients with TBI.