N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP) as a Potential Novel Treatment for Experimental Traumatic Brain Injury
Recommended Citation
Zhang Y, Zhang L, Chopp M, Zhang Z, Mahmood A, Xiong Y. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP) as a Potential Novel Treatment for Experimental Traumatic Brain Injury. J Neurotrauma 2024; 41(15-16):A117.
Document Type
Conference Proceeding
Publication Date
6-6-2024
Publication Title
J Neurotrauma
Abstract
Objective: N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) exhibits multiple functions, such as immunomodulation, anti-inflammation, anti-fibrosis, and pro-angiogenesis. This study was aimed to determine efficacy and mechanism of AcSDKP treatment for traumatic brain injury (TBI). Methods: Young (2-3 months) male Wistar rats were subjected to moderate TBI. Subcutaneous infusion of AcSDKP at a dose of 0.8 mg/kg/day or Vehicle (0.01N acetic acid) was initiated 1h after injury and continued for 3 days. Modified neurological severity score (mNSS), foot-fault, Morris water maze tests were performed. Animals were sacrificed 1 day or 35 days after injury and brain sections processed for histological analyses of neuronal loss, neuroinflammation, BBB damage, angiogenesis, neurogenesis and histone deacetylase 4 (HDAC4). One-way ANOVA followed by post hoc Tukey's tests was used to compare the differences in functional and histological outcomes. P value <0.05 was considered significant. Results: Compared to the Vehicle treatment, AcSDKP treatment led to significant (p<0.05): 1) improvements in spatial learning in the Morris water maze test and sensorimotor function in foot-fault and mNSS tests, 2) reductions of lesion volume and hippocampal neuronal cell loss (NeuN), BBB damage (Fibrin deposit), and neuroinflammation (CD68+ microglia/macrophages and GFAP+ astrocytes), 3) enhancement of angiogenesis (BrdU/EBA staining) and neurogenesis (BrdU/NeuN staining), and 4) blockage of neuronal HDAC4 nuclear translocation, which increased histone H3 acetylation in rats after TBI. Conclusions: Our data reveal a novel mechanism that AcSDKPinduced beneficial effects on TBI recovery are associated with its selective inhibition of neuronal HDAC4 nuclear translocation.
Volume
41
Issue
15-16
First Page
A117
