Objective      To investigate the effect of different apolipoprotein E (APOE=gene

apoE=protein) genotypes on the neuroprotective function of apoE mimetic peptide (COG1410) after early traumatic brain injury (TBI).       Methods      APOE targeted-replacement mice (ε3

ε4) and APOE knockout (APOE(-/-) mice were randomly allocated to a TBI+COG1410 group (n=30)

a TBI+normal saline group (n=30) and a sham operation group (n=10). The TBI+COG1410 group and the TBI+normal saline group each were further divided into 3 subgroups (1

3 and 7 d)

with 10 mice in each subgroup. TBI model was established by precision strike with a head injury impactor (PSI company

U.S.A)

and COG1410 solution or normal saline (1 mg/kg) was selectively administered through the tail vein within 30 min after TBI. Early TBI outcomes included neural function test (Rotorod latency) in the initial 7 days after TBI

cerebral edema and semi-quantitative expression of amyloid precursor protein (APP) in the pericontusional corpus callosum in 1

3 and 7 d.       Results      Among the mice with different APOE genotypes

ε3 mice demonstrated superior rotorod latency in the first 3 days after TBI as compared to ε4 mice (P0.05). After intravenous administration of COG1410 (1 mg/kg)

ε3 mice exhibited improved rotorod latency in 4-7 d after TBI (P0.05)

and decreased cerebral edema on the days 3 and 7 (P0.05)

while ε4 mice and APOE(-/-) mice exhibited improved Rotorod latency in 7 days after TBI (P0.05) and decreased cerebral edema on 1

3 and 7 d (P0.05). Moreover

COG1410 suppressed the APP expression in ε3 mice and APOE(-/-) mice in 1

3 and 7 d after TBI (P0.05)

but the APP levels had no statistically significant difference in ε4 mice.       Conclusion      APOEε4 gene as a high risk gene has a poor outcome in TBI. Moreover

apoE mimetic peptide can reduce early brain injury and improve the outcomes in the mice with APOEε3/3 genotype and APOEε4/4 genotype.