Neuroprotective and neurorestorative effects of thymosin β4 treatment initiated 6 hours after traumatic brain injury in rats.
OBJECTIVE
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.
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA. yxiong1@hfhs.org
Ye
Y
Xiong
Yanlu
Y
Zhang
Asim
A
Mahmood
Yuling
Y
Meng
Zheng Gang
ZG
Zhang
Daniel C
DC
Morris
Michael
M
Chopp
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D002540:Cerebral Cortex / Q000473:pathology; D018891:Dentate Gyrus / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013947:Thymosin / Q000494:pharmacology* / Q000627:therapeutic use; D000099201:Thymosin beta(4)
D018696:Neuroprotective Agents; D013947:Thymosin; D000099201:Thymosin beta(4)