Neuroprotective effects of tetracyclines on blunt head trauma: An experimental study on rats

ABSTRACTBackground: Prevention of primary damage caused by head trauma may be avoided with protective measures and techniques which is a public health concern. Experimental and clinical studies about treatment of head trauma were all centered to prevent secondary damage caused by physiopathological changes following primary injury. Neuroprotective features of tetracyclines were the focus of several experimental studies in the last decade. In the present study we aimed to investigate the neuroprotective effects of tetracycline in an experimental model of blunt brain injury in rats. Materials and Methods: 32 male Sprague‑Dawley rats were divided into four experimental groups (n = 8). Head trauma was not performed in control group (group 1, craniectomy only). In the second group, head trauma and craniectomy were performed. Intraperitoneal saline was used in addition to trauma and craniectomy for treatment in group 3 whereas intraperitoneal tetracycline and saline were used for treatment in group 4. Results: When histological examinations performed by transmission electron microscopy were evaluated,injury at ultrastructural level was demonstrated to be less pronounced in tetracycline group with decreased lipid peroxidation levels. Conclusion: In accordance with these findings, we conclude that systemic tetracycline administration is effective in reduction of secondary brain damage and brain edema and thus it may be considered as a therapeutic option.

IntroductionTraumatic brain injury usually involves an external impact targeting cranium and it is one of the leading causes of mortality and morbidity among young adults.[1] Head traumas in Turkey are usually associated with traffic accidents with an estimated mortality of 10/100.000. A thorough and detailed research focusing on head traumas is essential.[2‑5] The results of previous studies on neural trauma demonstrated two stages of injury defined as: Primary injury mainly linked to physical effect and secondary injury mainly associated with responses to primary effect.[6‑8] Trauma is well implicated as a major cause of primary brain injury. The primary effect which is beyond the scope of this paper may be managed by preventive health measures. Secondary injury may be defined as a metabolic response to primary effect and may be prevented if proper measures were not undertaken at a hospital setting.[9] Many mechanisms have been identified to contribute to secondary brain injury including rise of excitatory amino acids, generation of free oxygen radicals and arachidonic acid metabolites, high influx of Ca++ ions into the cytoplasm and development of lactic acidosis. Recently it has been shown that activation of caspase‑1 and caspase‑3 as well as generation of interleukin‑1 was an important step for triggering apoptosis and cell death.[10‑12] In fact, a simultaneous radical procedure is required to prevent steps involved in mechanisms of secondary brain injury and thus to manage traumatic inflammatory process. Tetracycline is an antimicrobial agent which has been shown to have neuroprotective effects including inhibition of caspase‑1 and 3, nitric oxide synthase,matrix metalloproteinases as well as glutamate excitotoxicity.[13‑15] So far, tetracyclines were proven to be beneficial against neuronal injury models.[16‑18] The enzymatic steps described in the above paragraph are important triggers for secondary injurious process which is involved in augmentation of primary injury. In the present study, we aim to investigate the neuroprotective effects of tetracycline on rat head trauma model of blunt cerebral injury in terms of mitochondrial and axonal degeneration as well as level of lipid peroxidation.