Fare Kafa Travmasi Modelinde Deksmedetomidinin İnflamasyon Üzerine Etkilerinin İncelenmesi
xmlui.mirage2.itemSummaryView.MetaDataShow full item record
Introduction & Objectives: Traumatic brain injury (TBI) is a leading cause of mortality and permanent or transient neurological disability worldwide. After primary damage, secondary damage processes begin, which last longer and cause loss of neurological function. Neuroinflammation, one of the responses to secondary damage, is an innate immune response to the pathogens or signaling molecules that result from cellular damage. The innate immune system is activated by "damage-associated molecular patterns" (DAMPs), which are released by damaged cells in sterile inflammation then inflammatory response begins. Activation of inflammasomes, which are a group of cytosolic multiprotein complexes, initiates the cleavage of pro-caspase-1 to the mature form of caspase-1 which is then able to cleave pro IL-1 and pro IL-18 into their mature forms of IL-1 and IL-18. In addition, later in the response, lymphocyte and microglia/macrophage activation is observed. Dexmedetomidine (DEX) is a potent and highly selective α2-adrenoceptor agonist which has analgesic and sedative properties without causing respiratory depression, and its antiinflammatory effects are shown in many experimental animal models. In this study, we aimed to investigate the antiinflammatory effects of intraperitoneal dexmedetomidine given in antiinflammatory and sedative doses, on the third day of inflammation in experimental traumatic brain injury model. Material & Methods: In this study, twenty male Swiss Albino mice were divided into four groups: sham (n=5), control (n=5), 40 µg/kg DEX (n=5) and 200 µg/kg DEX (n=5) injected groups. Closed head trauma was performed by using weight drop model (80 gr, 9 cm). Half an hour after the trauma, intraperitoneal saline was injected into the control group and intraperitoneal 40 and 200 μg / kg DEX were given to the experimental groups. Neurological evaluations of all the groups were performed with mNSS at the end of the first and third days. The mice were sacrified in the third day and histopathologic and immunohistochemical findings of the brain tissues were examined and compared with the control group. Results: A neurologically significant improvement was obtained with DEX given at 40 μg / kg dose (p = 0.024), but when 200 μg / kg DEX was given, the improvement was not found to be statistically significant (p = 0,06). IL-1β signal positivity was significantly reduced in the group given 200 μg / kg DEX compared to the control group (p = 0.028). The number of Iba-1 (Ionized calcium binding adaptor molecule-1) marked microglias which have migrated to the injury site was lower in the group that has been given 200 μg / kg DEX than the control group (p = 0.031). In the 40 and 200 μg / kg DEX groups, the number of active microglias was significantly lower than the control group (p = 0.0357 and p = 0.0357). When T lymphocyte infiltration was evaluated, the number of CD3 + cells were significantly lower in the group given 40 μg / kg DEX compared to the control group (p = 0,05). NLRP3 signal was significantly reduced in both of the drug-treated groups when compared to the control group (p = 0.031 and p = 0.031, respectively). Lastly, in histopathological examinations, cytotoxic edema decreased in experimental groups which were given DEX. Conclusion: In mice head trauma model, dexmedetomidine inhibits neuroinflammation and microglial activation that contributes to neurological recovery.