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

Laboratory investigation

Ye Xiong M.D., Ph.D. 1 , Yanlu Zhang M.D. 1 , Asim Mahmood M.D. 1 , Yuling Meng Ph.D. 1 , Zheng Gang Zhang M.D., Ph.D. 2 , Daniel C. Morris M.D. 3 , and Michael Chopp Ph.D. 2 , 4
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  • 1 Departments of Neurosurgery,
  • 2 Neurology, and
  • 3 Emergency Medicine, Henry Ford Health System, Detroit, Michigan; and
  • 4 Department of Physics, Oakland University, Rochester, Michigan
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Object

Thymosin β4 (Tβ4) is a regenerative multifunctional peptide. The aim of this study was to test the hypothesis that Tβ4 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 Tβ4 group (n = 8); and 3) 30 mg/kg Tβ4 group (n = 8). Thymosin β4 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 Tβ4 treatment.

Results

Compared with saline administration, Tβ4 treatment initiated 6 hours postinjury 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 with the low-dose treatment.

Conclusions

Thymosin β4 treatment initiated 6 hours postinjury provides both neuroprotection and neurorestoration after TBI, indicating that Tβ4 has promising therapeutic potential in patients with TBI. These data warrant further investigation of the optimal dose and therapeutic window of Tβ4 treatment for TBI and the associated underlying mechanisms.

Abbreviations used in this paper:BSA = bovine serum albumin; CCI = controlled cortical impact; mNSS = modified Neurological Severity Score; PBS = phosphate-buffered saline; Tβ4 = thymosin β4.

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Contributor Notes

Address correspondence to: Ye Xiong, M.D., Ph.D., Henry Ford Health System, Department of Neurosurgery, E&R Building, Room 3096, 2799 West Grand Boulevard, Detroit, Michigan 48202. email: yxiong1@hfhs.org.

Please include this information when citing this paper: published online February 10, 2012; DOI: 10.3171/2012.1.JNS111729.

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