Nanoparçaya Yüklenmiş Farnesiltiosalisilik Asit’in Kafa Travması Modelinde Nöroprotektif ve Antiödem Etkilerinin İncelenmesi

Abstract

Introduction & Objectives: Traumatic brain injury is the most frequently seen cause of death and severe morbidity among young population. Primary injury occurs as a result of post traumatic injury and in acute phase, mechanical tissue disruption, necrotic cell death, vascular injury, and axonal injury take place. The continuation of the primary injury within this period triggers a series of events which cause secondary injury. Accompanying the secondary injury, an increase in the derivatives of oxygen, apoptosis which is caused by the activation of transmitters like neurotoxic glutamate and intra- and extracellular mechanisms such as RAS/RAF/ERK/MAPK, necrosis and inflammation occur. For this reason, within days or weeks, functional and neurocognitive deficits happen. Previous studies in the literature that were carried out with the use of FTS for the prevention of secondary injury showed that FTS has positive effects on neuroprotection. The aim of this study is to apply Farnesylthiosalicylic acid (FTS), a RAS/MAPK inhibitor in experimental mice brain injury model, and investigate its effects on secondarily emergent neurocognitive disorder, contusion and cerebral edema. Materials & Methods: In this study, a total number of 25 male Swiss albino mice were used and with weight-drop model and under isoflurane anesthesia a close head injury was generated. As for the trauma volume, a moderate volume trauma was opted (67 gr, 7.5 cm). Those 25 mice in total were divided into 5 groups. One of the groups was sham surgery group. The other groups were designated as trauma groups. The control group was induced trauma only. One of the groups was given FTS after trauma, the other group FTS loaded on HNP and the last group solely HNP. Chemicals that mentioned before were given to the groups excluding the sham and control groups an hour after the trauma. The neurological assessments of all the groups at the end of the 24th hour and the 5th day were made by mNSS. After the neurological evaluation on the 5th day, all the groups had cranial MRI scan. Later, all the brains having sacrificed were painted with TTS and the infarct areas were examined. Findings: When ΔmNSS scores were compared at the end of the medical examinations performed on the 1st and 5th day, ΔmNSS scores were calculated as 1.2 ± 0,44 on the average for the control group, 2,8 for FTS applied group, 4,2 ±0,44 for FTS+HNP applied group, and 0,6 ±0,54 for the HNP group (vehicle). Compared to the control group, the neurological improvement in the FTS+HNP applied group had statistical significance (p=0,008). The neurological improvement in the FTS applied group did not have statistical significance compared to the control group (p=0,056). In comparison with the FTS applied group, the neurological improvement wasn’t found to be statistically significant, either (p=0,095). When the contusion volumes in MRI were examined, it was seen that the contusion volume in the FTS+HNP applied group was %70 smaller compared to the control group and statistically significant (p=0,008), and the contusion volume in the FTS applied group was found to be %53 smaller compared to the control group and have statistical significance. As a result of the comparison between the FTS+HNP group and FTS applied group, it was seen that the application of FTS loaded on nanoparticle didn’t have a statistical superiority to the stand alone use of FTS (p=0,151). Finally, the brains of the sacrificed animals treated with TTS after slicing process were inspected and compared to the control group, a %60 smaller infarct area was observed in the FTS+HNP applied group, which had statistical significance (p=0,008), and in comparison with the control group, the infarct volume in the FTS applied group was %45 smaller and statistically significant (0,008). The application of FTS loaded on HNP was seen to have reduced the infarct volume in comparison to the mere application of FTS but the reduction didn’t have statistical significance (p=0,095).

Conclusion: For moderate traumatic brain injury, the use of FTS loaded on nanoparticle resulted in neurological improvement, radiological reduction of contusion volumes in MRG and shrinking of infarct areas ensued from contusion. Administration of FTS loaded nanoparticle after traumatic brain injury is a novel approach to effectively reduce secondery brain injury.