Neuroprotective effects of NAAG peptidase inhibition on the treatment of traumatic brain injury

Objective To explore the neuroprotective effects of NAAG peptidase inhibition on the treatment of traumatic brain injury.Method A total of 20 male Sprague-Dawley rats were divided into 4 groups,then sustained to moderate lateral fluid percussion TBI.A novel NAAG peptidase inhibitor,ZJ-43,was used in4 different doses (0,50,100,or 150 mg/kg).Each dose was repeatedly administered i.p.(n=5/group) by multiple injections at 3 times (0 h,8 h,16 h) after TBI.Rats were euthanized at 24 hrs after TBI and brains were processed and stained according to the Fluoro-Jade B Histofluorescence and GFAP Immunohistochemistry protocols,lpsilateral neuronal degeneration and bilateral astrocyte loss in the CA2/3 regions of the hippocampus were quantified using stereological techniques.Results Compared with vehicle,ZJ-43 significantly reduced the number of the ipsilateral degenerating neurons (P＜0.01) with the greatest neuroprotection at the 50 mg/kg dose.Moreover,50 mg/kg of ZJ-43 also significantly reduced the ipsilateral astrocyte loss (P＜0.05 ).Conclusions Blockade of NAAG peptidases may augment an endogenous neuroprotective mechanism in the brain and limit glutamate excitotoxicity.The strategy may represent a new therapeutic approach to secondary brain damage after traumatic brain injury. Key words: Traumatic brain injury;  N-acetylaspartylglutamatc (NAAG);  Glutamate; Excitotoxicity;  Neuroprotection