Neuroprotective and neurorestorative effects of thymosin β4 treatment initiated 6 hours after traumatic brain injury in rats

Object. Thymosin beta 4 (T beta 4) is a regenerative multifunctional peptide. The aim of this study was to test the hypothesis that T beta 4 treatment initiated 6 hours postinjury reduces brain damage and improves functional recovery in rats subjected to traumatic brain injury (TBI). Methods. Traumatic brain injury was induced by controlled cortical impact over the left parietal cortex in young adult male Wistar rats. The rats were randomly divided into the following groups: 1) saline group (n = 7); 2) 6 mg/kg T beta 4 group (n = 8); and 3) 30 mg/kg T beta 4 group (n = 8). Thymosin beta 4 or saline was administered intraperitoneally starting at 6 hours postinjury and again at 24 and 48 hours. An additional group of 6 animals underwent surgery without TBI (sham-injury group). Sensorimotor function and spatial learning were assessed using the modified Neurological Severity Score and the Morris water maze test, respectively. Animals were euthanized 35 days after injury, and brain sections were processed to assess lesion volume, hippocampal cell loss, cell proliferation, and neurogenesis after T beta 4 treatment. Results. Compared with saline administration, T beta 4 treatment initiated 6 hours postinjury significantly improved sensorimotor functional recovery and spatial learning, reduced cortical lesion volume and hippocampal cell lass, and enhanced cell proliferation and neurogenesis in the injured hippocampus. The high dose of T beta 4 showed better beneficial effects compared with the low-dose treatment. Conclusions. Thymosin beta 4 treatment initiated 6 hours postinjury provides both neuroprotection and neurorestoration after TBI, indicating that T beta 4 has promising therapeutic potential in patients with TBI. These data warrant further investigation of the optimal dose and therapeutic window of T beta 4 treatment for TBI and the associated underlying mechanisms. (http://thejns.org/doi/abs/10.3171/2012.1.JNS111729)