Manifestations of neuroinflammation 30 days after experimental traumatic brain injury in rats

Abstract

Traumatic brain injury (TBI) often leads to the development of a progressive chronic painful condition, caused by secondary neuroinflammation with alternating waves of inflammation and resolution. The molecular and cellular mechanisms that determine the progression of neuropathology during TBI are poorly understood, that leads to the lack of effective treatment for the long-term consequences of TBI.

Aim: To determine the behavioral characteristics of animals, functional state of lymphocytes, cytokine and toll like receptor 4 (TLR4) gene expression in the hypothalamus of traumatized rats on the 30^th day after traumatic brain injury and their changes after administration of recombinant receptor antagonist IL-1 (rIL-1RA).

Materials and methods: The study was performed on Wistar rats. A "weight-drop" model was used to induce moderate TBI. rIL-1RA (50 mg/kg) was administered subcutaneously 1 hour after TBI and then every day for 2 days. Behavioral reactions were assessed in the open field test. Gene expression of IL-1β, IL-10, TNFα, TLR4 in the hypothalamus, as well as proliferative and cytotoxic activities of spleen lymphocytes were determined.

Results. On the 30^th day after TBI, untreated animals showed reduced distance and speed of movement, increased frequency and duration of freezing acts, decreased number of vertical rears and explored holes. In the hypothalamus, the gene expression of cytokines was significantly higher in untreated rats compared to control animals, as well as TLR4 gene expression. Treatment with rIL-1RA had no influence on anxious behavior and lymphocytes functions, and led to elevated gene expression of cytokines, but decreased expression of TLR4 gene.

Conclusion: Persistent neuroinflammation on the 30^th day after TBI is manifested by anxious behavior and high expression of cytokines and TLR4 genes in the hypothalamus. The administration of rIL-1RA in the early post-traumatic period does not prevent behavioral changes and to some extent reduces the hypothalamic disorders detected in injured animals.