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

Abstract

Object Thymosin beta 4 (Tβ4) is a regenerative multifunctional peptide. This study will test the hypothesis that Tβ4 treatment initiated 6 hours post-injury reduces brain damage and improves functional recovery in rats after traumatic brain injury (TBI). Methods TBI was induced by controlled cortical impact over the left parietal cortex. Young adult male Wistar rats with TBI were randomly divided into the following groups: 1) Saline group (n=7); 2) Tβ4-6 mg/kg group (n=8), and 3) Tβ4-30 mg/kg group (n=8). Tβ4 or saline was administered intraperitoneally starting at 6 hours post-injury and then repeated daily at 24 and 48 hours. An additional group of sham animals underwent surgery without injury (n=6). Sensorimotor function and spatial learning were assessed using a modified neurological severity score and Morris water maze tests, respectively. Animals were sacrificed 35 days after injury and brain sections processed to assess lesion volume, hippocampal cell loss, cell proliferation and neurogenesis after Tβ4 treatment. Results Compared to saline, Tβ4 treatment initiated 6 hours post-injury significantly improved sensorimotor functional recovery and spatial learning, reduced cortical lesion volume and hippocampal cell loss, and enhanced cell proliferation and neurogenesis in the injured hippocampus. The high dose of Tβ4 showed better beneficial effects compared to the low-dose treatment. Conclusions Tβ4 treatment initiated 6 hours post-injury provides both neuroprotection and neurorestoration after TBI, indicating that Tβ4 has promising therapeutic potential in TBI patients. These data warrant further investigation of the optimal dose and therapeutic window of Tβ4 treatment for TBI and the associated underlying mechanisms.

Thymosin <i>β</i>4 Improves Neurological Outcome and Enhances Induced Oligodendrogenesis in the Rat after ICH

“…The most frequent adverse events are headache and upper respiratory infection. According to these findings and our previous studies in stroke and TBI [20] [26], the mid-level doses ranged from 3 -12 mg/kg. A biodistribution study of synthetic Tβ4 in normal mice provides evidence that intraperitoneal injection of 400 µg Tβ4 increases the concentrations of Tβ4 significantly in a variety of organs from the first 40 min to 2 h after injection compared to baseline concentrations.…”

Beneficial effects of thymosin β4 on spinal cord injury in the rat

“…Tb4 is ubiquitously distributed in almost all cells with relatively higher levels in platelets and white blood cells . The angiogenesis, anti-inflammation, wound repair, cell survival and neuroprotective properties of Tb4 (Morris et al, 2010;Plemel et al, 2008;Semler et al, 2011;Smart et al, 2007;Xiong et al, 2011Xiong et al, , 2012Zhang et al, 2009) make Tb4 a good candidate molecule to aid in SCI recovery. The safety, tolerability, and efficacy of Tb4 have been evaluated in patients with ischemic heart disease and venous ulcers (Crockford, 2007;Goldstein et al, 2012;Guarnera et al, 2007Guarnera et al, , 2010.…”

Function of Thymosin Beta-4 in Ethanol-Induced Microglial Activation

“…Neonatal C57BL/6 mice (female) were randomly divided into three groups: (1) normal mice (n = 7); (2) ethanol treated mice (n = 8); and (3) ethanol +Tβ4 (6 mg/ kg) [16] group (n = 8). We used a synthetic copy of the naturally-occurring 43-amino acid Tβ4 peptide (RegeneRx, Bethesda, MD, USA).…”