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Introduction & Objectives: Traumatic brain injury (TBI) is one of the major causes of death among young people in the world. TBI is an important public health problem in recent years and is the most common cause of disability and death worldwide. After the trauma, the response of the cells and the activated molecular pathways differ depending on the time elapsed after the formation of damage. Microglia, acivates proinflammatory cytokines such as TNF-α, IL-1β and IL-6. After the acute period, inflammasome (NLRP3), are activated. As a result, the caspase enzyme, is transformed into its active form. Activated caspase-1 stimulates the release of IL-1β and IL-18 cytokines, which play a role in inflammatory events. Doxycycline is a Food and Drug Administration (FDA) approved antibiotic and can pass through the blood-brain barrier and inhibits nitric oxide (NO), TNF alpha, IL-1, IL-6, IL-8. In this study, we aimed to investigate the antiinflammatory effects of intraperitoneal doxycycline given in low and high doses, on the third day after the head trauma 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), 10 mg/kg DOX (n=5) and 100 mg/kg DOX (n=5) injected groups. Closed head trauma was performed by using weight drop model (75 gr, 11 cm). 30 minutes after the trauma, intraperitoneal saline was injected into the control group and intraperitoneal 10 and 100 mg/kg DOX were given to the experimental (low dose, high dose) groups. Histopathologic and immunohistochemical findings of the brain tissues were examined and compared with the control group. Results: IL-6 signal positivity significantly decreased in the group that received 10 mg/kg DOX (p = 0.003). There was a decrease in the number of positive cells in the group given 100 mg/kg DOX, but this decrease was not statistically significant (p= 0.58). It is observed that the migration of microglia marked with Iba-1 to the damaged area is lower in both groups given 10 mg/kg and 100 mg/kg DOX compared to the control group (p = 0.0001, p = 0.003). CD-3 signal positivity and positive cell count decreased significantly in both groups given 10 mg/kg and 100 mg/kg DOX (p = 0.00001, p = 0.003). Finally, the TUNEL (+) neuron and glia cell numbers with apoptosis decreased significantly in both low and high DOX groups compared to the trauma group. Conclusion: The use of DOX in head trauma has inhibited neuroinflammation and microglial activation. Therefore, administration of doxycycline after traumatic brain injury is a novel approach to effectively reduce secondery brain injury aggrevated by the acute neuroinflammatory response. Gereç ve Yöntem: Çalışmada, 4 ayrı grup (sham, kontrol, düşük ve yüksek doz DOX) ve her grupta 5 fare (n=5) olacak şekilde toplam 20 adet fare kullanılmıştır. Hayvanlara 11 cm yükseklikten 75 gr serbest ağırlık düşürülerek kafa travması modeli oluşturulmuştur. Travmadan yarım saat sonra kontrol grubuna serum fizyolojik, düşük doz grubuna 10 mg/kg ve yüksek doz grubuna 100 mg/kg intraperitoneal doksisiklin enjeksiyonu yapılmıştır. Hayvanlar üçüncü günde sakrifiye edilerek beyin dokularındaki histopatolojik ve immünhistokimyasal bulgular kontrol grubuyla karşılaştırılmıştır. Bulgular: IL-6 sinyal pozitifliği, 10 mg/kg DOX verilen grupta anlamlı olarak azalmıştır (p=0,003). 100 mg/kg DOX verilen grupta pozitif hücre sayısında azalma görülmüştür, fakat bu azalma istatistiksel olarak anlamlı bulunmamıştır (p=0,58). Iba-1 (İyonize kalsiyum bağlayıcı adaptör molekül-1) ile işaretlenen mikrogliaların hasarlı bölgeye göçünün, kontrol grubuna göre 10 mg/kg ve 100 mg/kg DOX verilen gruplarda daha az olduğu görülmektedir (p=0,0001, p=0,003). CD-3 sinyal pozitifliği ve pozitif hücre sayısı, 10 mg/kg ve 100 mg/kg DOX verilen gruplarda anlamlı olarak azalmıştır (p=0,00001, p=0,003). Son olarak, düşük ve yüksek doksisiklin verilen travma gruplarında, ilaçsız travma grubuna göre daha yüksek oranda apoptoza gitmeyen nöron ve glia oranları görüldmüştür. Sonuç: Kafa travmasında DOX kullanımı, akut nöroinflamasyon ve mikroglia aktivasyonunu inhibe ederek kafa travması sonrası ortaya çıkan ikincil hasarın azaltmasında etkin olarak kullanılabilecek yeni bir tedavi yöntemi olarak umut vaat etmektedir.