Interleukin-4 Reduces Lesion Volume and Improves Neurological Function in the Acute Phase after Experimental Traumatic Brain Injury in Mice

Abstract

Little is known about the impact of interleukin-4 (IL-4) on secondary brain damage in the acute phase after experimental traumatic brain injury (TBI). Therefore, we evaluated the effect of IL-4-Knockout (IL-4-KO) on structural damage, as well as functional impairment, in the acute phase after experimental TBI in mice. A total of 28 C57Bl/6 wildtype and 20 C57BL/6-Il4tm1Nnt/J IL-4-KO mice were subjected to controlled cortical impact (CCI). Contusion volumes, body weight and functional outcome (Video Open Field Test [VOF], Hole Board Test [HB], CatWalkXT®) were determined on post-operative Days 1 (D1), 3 (D3), and 7 (D7). Contusion volume (13.45 ± 0.88 mm3 vs. 9.50 ± 0.97 mm3, p = 0.015) and weight loss (-2.92 ± 0.52% vs. -0.85 ± 0.67%, p = 0.027) were significantly higher and exploration behavior significantly more impaired (e.g., 150.44 ± 18.71 fields explored vs. 211.56 ± 18.90 fields explored, p = 0.028 in the VOF; 23.31 ± 2.03 holes explored vs. 35.65 ± 1.93 holes explored, p < 0.001 in the HB) in IL-4-KO mice on D1. Gait impairment was significantly more pronounced in IL-4-KO mice throughout the first week after CCI (e.g., 0.07 ± 0.01 sec vs. 0.00 ± 0.01 sec, p = 0.047 for right hindpaw Swing on D1; -1.76 ± 1.34 U vs. 2.53 ± 0.90 U, p = 0.01 for right forepaw mean intensity on D3; -0.01 ± 0.01 cm2 vs. 0.05 ± 0.01 cm2, p = 0.015 for left forepaw mean area on D7). In conclusion, IL-4 reduces structural damage and improves functional outcome in the acute phase after CCI. Neurobehavioral outcome assessment in IL-4-related studies should focus on motor function on the first 3 days after trauma induction.