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 μg/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-1β, 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-1β 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.

Lipoxygenases are a family of lipid-oxidizing enzymes, which generate eicosanoids and related compounds from arachidonic acid and other polyunsaturated fatty acids. These metabolites play important roles in physiology and pathogenesis of host defense mechanisms, cardiovascular diseases, cancer, inflammatory, allergic and neurodegenerative diseases. The 12/15-lipoxygenase (LOX) is special in that it can directly oxidize lipid membranes containing polyunsaturated fatty acids, without the preceding action of a phospholipase, leading to the direct attack on membranous organelles, such as mitochondria. The cytotoxic activity of human 12/15-LOX is up-regulated in neurons and endothelial cells especially after a stroke and thought to contribute to both neuronal cell death and blood-brain barrier leakage. The discovery of inhibitors that selectively target recombinant 12/15-LOX in vitro, as well as possessing activity against the murine orthologous ex vivo, could potentially support a novel therapeutic strategy for the treatment of stroke and other brain disorders related to 12/15-LOX. Here we reviewed 12/15-LOX chemistry shortly, and the diseases in which 12/15-LOX has a role in their pathophysiology and recent advances of 12/15-LOX inhibitors as a treatment option for neurological diseases.

No abstract

No abstract