Work

Therapeutic Effects of N -Acetyl-Seryl-Aspartyl-Lysyl-Proline on Functional Recovery in Male and Female Rats after Traumatic Brain Injury

Year: 2026

Type: article

Abstract: Our previous study demonstrated that a single dose of N -acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) improves functional recovery in male rats after traumatic brain injury (TBI). The present study is designed to determine the therapeutic effects of varying AcSDKP doses in both female and male rats following TBI. Young Wistar rats were randomly assigned to the Sham or TBI group treated with Vehicle or AcSDKP (0.4, 0.8, or 1.6 mg/kg/day; n = 8/group/sex). AcSDKP was administered subcutaneously via osmotic pumps for 3 days starting 1 h after injury. Sensorimotor function (foot fault, adhesive removal, and modified Neurological Severity Score) was assessed longitudinally. Spatial learning and memory were evaluated using the Morris water maze. Histological analyses were performed at 35 days post-injury. AcSDKP treatment significantly improved sensorimotor and cognitive function and reduced cortical lesion volume and neuronal loss in both sexes compared with vehicle controls ( p < 0.05). These functional improvements were accompanied by decreased microglial/macrophage activation (CD68) and reduced astrocyte reactivity (glial fibrillary acidic protein), indicating attenuation of neuroinflammation. AcSDKP at 0.8 mg/kg/day consistently yielded the greatest improvements across outcomes in both sexes, whereas the higher dose (1.6 mg/kg/day) did not further enhance efficacy, indicating a potential ceiling effect or a nonlinear treatment pattern. These results demonstrate dose-related neuroprotective and anti-inflammatory effects of AcSDKP on TBI, with 0.8 mg/kg/day as the most effective dose among those tested, supporting further translational development.

Source: Neurotrauma Reports

DOI: 10.1177/2689288x261480487