Thymosin Beta 4

Neurorestorative Treatments for Traumatic Brain Injury

Thymosin beta 4 (Tβ4), a polypeptide of 43-amino acids, was first isolated from bovine thymus tissue and subsequently found to exist in all mammals studied. The major intracellular function of Tβ4 is G-actin-sequestration, which is necessary for cell motility and organogenesis (Crockford, 2007). Recent studies demonstrate that Tβ4 is a multifunctional peptide. It inhibits inflammation and apoptosis, and promotes tissue repair in skin, cornea, and heart (Morris et al., 2010b). Tβ4 is an essential paracrine factor of EPCs, and Tβ4 promotes angiogenesis after ischemic injury (Smart et al., 2007). Safety, tolerability and efficiency of Tβ4 are being evaluated in clinical patients with acute myocardial infarction (Crockford, 2007).

Tβ4 plays a critical role in many cellular processes including mobility, axonal path-finding, neurite formation, proliferation and neuronal survival (Morris et al., 2010b; Sun and Kim, 2007). Our recent study demonstrates that Tβ4 improves neurological functional recovery in mice with experimental autoimmune encephalomyelitis (Zhang et al., 2009a) and in rats with embolic stroke (Morris et al., 2010a). Tβ4 is a potential treatment for TBI. Tβ4 (6 mg/kg) was administered ip starting at day 1 and then every 3 days for an additional 4 doses to the TBI rats (Xiong et al., 2010b). Neurological functional recovery was evaluated. Animals were euthanized 35 days after injury and brain sections were stained for immunohistochemistry to assess angiogenesis, neurogenesis, and oligodendrogenesis after Tβ4 treatment. Delayed Tβ4 treatment did not affect lesion volume but significantly reduced hippocampal cell loss, enhanced angiogenesis and neurogenesis in the injured cortex and hippocampus, increased oligodendrogenesis in the CA3 region, and significantly improved sensorimotor functional recovery and spatial learning compared to the saline treatment. These data demonstrate that administration of Tβ4 significantly improves histological and functional outcomes in rats with TBI, indicating that Tβ4 has considerable therapeutic potential in TBI patients. Further investigation of Tβ4 is warranted for the treatment of TBI